ABSTRACT
Fe, Cr, and W are important elements in the alloys of in-reactor materials and operate in high-temperature environments with thermal expansion. Their tritium-impeding abilities are crucial to the radiation safety of various nuclear reactors. In this study, first-principles density functional theory is combined with quasi-harmonic approximation to evaluate factors that can affect the interstitial formation energy and diffusion coefficient of hydrogen isotopes in body-centered cubic (BCC) Fe, Cr, and W, including thermal expansion, metal host lattice vibrations, phonon density-of-states (pDOS) coupling diffusing atoms, and isotope effects. Calculation results indicate that the interstitial formation energy decreases as lattice expansion increases, whereas the jump barriers remain almost constant. Thermal expansion, host lattice vibration, and pDOS coupling minimally affect the diffusion coefficients of hydrogen isotopes in Fe, Cr, and W. The diffusion coefficient ratios between hydrogen isotopes are higher than the inverse ratio of the square root of the isotope mass at low temperatures. However, they decrease to the inverse ratio of the square root of the isotope mass at temperatures exceeding 800 K. This study comprehensively investigates factors that affect the diffusion coefficients of hydrogen isotopes in BCC Fe, Cr, and W, thus providing a firm theoretical foundation for predicting the diffusion coefficients of tritium at different temperatures using protium/deuterium diffusion coefficients.
ABSTRACT
An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.
ABSTRACT
Exopolysaccharide produced by lactic acid bacteria has various functions. In the present study, one anti-oxidant polysaccharide fraction, namely S1-EPS, was extracted and purified from Pediococcus acidilactici S1, and its structure and its potential effect on the gel properties of fat substitute meat mince were investigated. The results showed that S1-EPS, one of homogeneous polysaccharides, was mainly composed of Gal, Glc, and Man in molar ratio of 7.61: 15.25: 77.13 and molecular weight of 46.975â¯kDa. The backbone of EPS-S1 contained â2,6)-α-D-Manp-(1âï¼â2)-α-D-Manp-(1â,â3)-α-D-Glcp-(1â¯ââ¯and a small amount ofâ6)-ß-D-Manp-(1â. The linkages of branches in EPS-S1 were mainly composed of α-D-Manp-(1â attached to a sugar residue â2,6)-α-D-Manp-(1âO-2 or ß-D-Galp-(1â attached to a sugar residue â2,6)-α-D-Manp-(1âO-6. Furthermore, as S1-EPS increased, the meat minced gel pores decreased, and the surface became smooth. A remarkable inhibitory effect on the lipid oxidation of meat minced gel was found as S1-EPS concentration increased. Overall, S1-EPS was found to have substantial potential in low-fat meat products by serving as a natural, anti-oxidant, and functional additive.
Subject(s)
Fat Substitutes , Pediococcus acidilactici , Polysaccharides, Bacterial , Polysaccharides, Bacterial/chemistry , Pediococcus acidilactici/metabolism , Pediococcus acidilactici/chemistry , Fat Substitutes/chemistry , Molecular Weight , Antioxidants/chemistry , Antioxidants/pharmacology , Gels/chemistry , Meat Products/microbiologyABSTRACT
Liquid confined in a nanochannel or nanotube has exhibited a superfast transport phenomenon, providing an ideal heat and mass transfer platform to meet the increasingly stringent challenge of thermal management in developing high-power-density nanoelectronics and nanochips. However, understanding the thermal transport of confined liquid is currently lacking and is speculated to be fundamentally different from that of bulk counterparts due to the unprecedented thermodynamics of liquid in nanoconfined environments. Here, we report that the thermal conductivity of water confined in a silica nanotube is nearly 2-fold as that of bulk status. Further molecular dynamics simulations reveal that this unusual enhancement originates from the densification and reorientation of local hydrogen bonds close to the nanotubes. Thermal-confinement scaling law is established and quantitatively supported by comprehensive simulations with remarkable agreement. Our findings lay a theoretical foundation for designing nanofluidics-enabled cooling strategies and devices.
ABSTRACT
The effective integration of nanomaterials with underlying current collectors is a key factor affecting the performance of nonenzymatic glucose sensors, where an inappropriate integration structure often leads to poor electron transport and instability. In this work, a seamless integrated electrode was constructed by the in situ immobilizing of a nickel-based metal-organic framework (Ni-MOF) on a three-dimensional (3D) conductive nickel foam (NF) for highly sensitive and durable glucose sensing. Facilitated by a rapid microwave-assisted reaction, a robust interfacial interaction between the Ni-MOF and the substrate was established through in situ conversion from nickel oxide (NiO). The fabricated Ni-MOF/NF electrode exhibits an excellent limit of detection (LOD) of 2.65 µM and an impressive sensitivity (14.31 mA cm-2 mM-1) within the linear range (4-576 µM), which is significantly boosted compared with that of an electrode prepared by a typical drop-casting method (3.56 mA cm-2 mM-1 in 4-1836 µM). Characterization and electrochemical tests reveal that this integrated structure on the one hand contributes to fast electron transport and thus has enhanced sensitivity and on the other hand leads to exceptional durability with its structural integrity maintained under bending, shaking, and ultrasonication. Moreover, this seamless integration method was also employed to immobilize the Ni-MOF converted from the pre-chemically deposited NiO layer on another type of substrate, 3D carbon paper (CP), demonstrating the versatility of this facile strategy in creating diverse electrochemical electrodes for applications beyond glucose sensing.
ABSTRACT
To address the growing and urgent need for quick and accurate food spoilage detection systems as well as to reduce food resource wastage, recent research has focused on intelligent bio-labels using pH indicators. Accordingly, we developed a dual-channel intelligent label with colorimetric and fluorescent capabilities using black lycium anthocyanin (BLA) and 9,10-bis(2,2-dipyridylvinyl) anthracene (DSA4P) as colorimetric and fluorescent indicators within a composite film consisting of chitosan (Cs), whey protein (Wp), and sodium tripolyphosphate (STPP). The addition of STPP as a cross-linking agent significantly improved the hydrophobicity, mechanical properties, and thermal stability of the Cs/Wp composite films under low pH conditions. After the incorporation of BLA and DSA4P, the resulting dual-channel intelligent label (Cs/Wp/STPP/BLA/DSA4P) exhibited superior hydrophobicity, as indicated by a water contact angle of 78.03°. Additionally, it displayed enhanced mechanical properties, with a tensile strength (TS) of 3.04 MPa and an elongation at break (EAB) of 81.07 %, while maintaining a low transmittance of 28.48 % at 600 nm. After 25 days of burial in soil, the label was significantly degraded, which showcases its eco-friendly nature. Moreover, the label could visually detect color changes indicating volatile ammonia concentrations (25-25,000 ppm). The color of the label in daylight gradually shifted from brick-red to light-red, brownish-yellow, and finally light-green as the ammonia concentration increased. Correspondingly, its fluorescence transitioned from no fluorescence to green fluorescence with increasing ammonia concentration, gradually intensifying under 365-nm UV light. Furthermore, the label effectively monitored the freshness of shrimp stored at temperatures of 4 °C, 25 °C, and - 18 °C. Thus, the label developed in this study exhibits significant potential for enhancing food safety monitoring.
Subject(s)
Chitosan , Lycium , Polyphosphates , Animals , Ammonia , Colorimetry , Whey Proteins , Seafood , Coloring Agents , Anthocyanins , Crustacea , Hydrogen-Ion Concentration , Food PackagingABSTRACT
Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited. In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD. Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM. A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results: The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis. The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM. Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP. We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug. Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Mice , Animals , Carcinoma, Hepatocellular/pathology , Vitamin D-Binding Protein/therapeutic use , Liver Neoplasms/pathology , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/metabolism , Cell Differentiation , Cell Line, TumorABSTRACT
Background: Ligand-mediated liposomes targeting folate receptors (FRs) that are overexpressed on the surface of tumor cells may improve drug delivery. However, the properties of liposomes also affect cellular uptake and drug release.
Objective: Mitoxantrone folate targeted liposomes were prepared to increase the enrichment of drugs in tumor cells and improve the therapeutic index of drugs by changing the route of drug administration.
Methods: Liposomes were prepared with optimized formulation, including mitoxantrone folatetargeted small unilamellar liposome (MIT-FSL), mitoxantrone folate-free small unilamellar liposome (MIT-SL), mitoxantrone folate-targeted large unilamellar liposome (MIT-FLL), mitoxantrone folate-free large unilamellar liposomes (MIT-LL). Cells with different levels of folate alpha receptor (FRα) expression were used to study the differences in the enrichment of liposomes, the killing effect on tumor cells, and their ability to overcome multidrug resistance.
The results of the drug release experiment showed that the particle size of liposomes affected their release behavior. Large single-compartment liposomes could hardly be effectively released, while small single-compartment liposomes could be effectively released, MIT-FSL vs MIT-FLL and MIT-SL vs MIT-LL had significant differences in the drug release rate (P<0.0005). Cell uptake experiments results indicated that the ability of liposomes to enter folic acid receptor-expressing tumor cells could be improved after modification of folic acid ligands on the surface of liposomes and it was related to the expression of folate receptors on the cell surface. There were significant differences in cell uptake rates (p<0.0005) for cells with high FRα expression (SPC-A-1 cells), when MIT-FSL vs MIT-SL and MIT-FLL vs MIT-LL. For cells with low FRα expression (MCF-7 cells), their cell uptake rates were still different (p<0.05), but less pronounced than in SPC-A-1 cells. The results of the cell inhibition experiment suggest that MIT-FLL and MIT-LL had no inhibitory effect on cells, MIT-FSL had a significant inhibitory effect on cells and its IC50 value was calculated to be 4502.4 ng/mL, MIT-SL also had an inhibitory effect, and its IC50 value was 25092.1 ng/mL, there was a statistical difference (p<0.05), MIT-FSL had a higher inhibitory rate than MIT-SL at the same drug concentration. Afterward, we did an inhibitory experiment of different MIT-loaded nanoparticles on MCF-7 cells compared to the drug-resistant cells (ADR), Observing the cell growth inhibition curve, both MIT-FSL and MIT-SL can inhibit the growth of MCF-7 and MCF-7/ADR cells. For MCF- 7 cells, at the same concentration, there is little difference between the inhibition rate of MITFSL and MIT-SL, but for MCF-7/ADR, the inhibition rate of MIT-FSL was significantly higher than that of MIT-SL at the same concentration (P<0.05).
Conclusion: By modifying folic acid on the surface of liposomes, tumor cells with high expression of folic acid receptors can be effectively targeted, thereby increasing the enrichment of intracellular drugs and improving efficacy. It can also change the delivery pathway, increase the amount of drug entering resistant tumor cells, and overcome resistance.
.Subject(s)
Liposomes , Mitoxantrone , Humans , Mitoxantrone/pharmacology , Cell Line, Tumor , Drug Delivery Systems/methods , Carrier Proteins/metabolism , Ligands , Folic AcidABSTRACT
Phytoremediation, which is commonly carried out through hydroponics and substrate-based strategies, is essential for the effectiveness of nature-based engineered solutions aimed at addressing excess nitrogen in aquatic ecosystems. However, the performance and mechanisms of plants involving nitrogen removal between different strategies need to be deeply understood. Here, this study employed in-situ cultivation coupled with static nitrogen tracing experiments to elucidate the influence of both strategies on plant traits associated with nitrogen removal. The results indicated that removal efficiencies in plants with substrate-based strategies for ammonium nitrogen and nitrate nitrogen were 30.51-71.11 % and 16.82-99.95 %, respectively, which were significantly higher than those with hydroponics strategies (25.98-58.18 % and 7.29-79.19 %, respectively). Similarly, the plant nitrogen uptake rates in the substrate-based strategy also generally showed higher levels compared to hydroponics strategies (P < 0.05). Meanwhile, the microorganisms-mediated nitrous oxide emission rates in the substrate-based strategy during summer (unamended: 0.00-0.58 µg/g/d; potential: 3.35-7.65 µg/g/d) were obviously lower than those in the hydroponics strategy (unamended: 2.23-11.70 µg/g/d; potential: 9.72-43.09 µg/g/d) (P < 0.05). Notably, analysis of similarity tests indicated that the influences of strategy on the above parameters generally surpass the effects attributable to interspecies plant differences, particularly during summer (R > 0, P < 0.05). Based on statistical and metagenomic analyses, this study revealed that these differences were driven by the stabilizing influence of substrate-based strategy on plant roots and enhancing synergistic interplay among biochemical factors within plant-root systems. Even so, phytoremediation strategies did not significantly alter the characteristics of plants with regards to their tendency towards ammonium nitrogen uptake (up to 87.68 %) and dissimilatory nitrate reduction to ammonium as primary biological pathway for nitrogen transformation which accounted for 53.66-96.47 % nitrate removal. In summary, this study suggested that the substrate-based strategy should be a more effective strategy for enhancing the nitrogen removal ability of plants in subtropical river restoration practices.
Subject(s)
Ammonium Compounds , Nitrates , Ecosystem , Biodegradation, Environmental , Rivers , Nitrogen/metabolism , DenitrificationABSTRACT
The cancer-promoting lncRNA HOTAIR has multiple isoforms. Which isoform of HOTAIR accounts for its expression and functions in cancer is unknown. Unlike HOTAIR's canonical intergenic isoform NR_003716 (HOTAIR-C), the novel isoform NR_047517 (HOTAIR-N) forms an overlapping antisense transcription locus with HOXC11. We identified HOTAIR-N as the dominant isoform that regulates the gene expression programs and networks for cell proliferation, survival, and death in cancer cells. The CpG island in the HOTAIR-N promoter was marked with epigenetic markers for active transcription. We identified a G-quadruplex (G4) motif rich region in the HOTAIR-N CpG island. Our findings indicate that G4s in HOTAIR-N CpG island is critical for expression of HOTAIR-N in cancer cells. Disruption of G4 may represent a novel therapeutic approach for cancer. The transcriptomes regulated by HOTAIR-N and Bloom in cancer cells as provided herein are important resources for the exploration of lncRNA, DNA helicases, and G4 in cancer.
ABSTRACT
To improve the reliability of strapdown inertial navigation system (SINS)/Doppler radar/odometer integrated navigation system, the federated Kalman filter with two-stage fault detection structure is designed, and a fault-tolerant SINS/Doppler radar/odometer integrated navigation method is proposed. Firstly, the pre-fault detection module sets before the local filter, and the residual chi-square test in the carrier coordinate system is selected to detect the abrupt faults of Doppler radar and odometer. Then, the secondary-fault detection module emplaces between the local filter and the main filter, and the sequential probability ratio test (SPRT) is selected to further detect the ramp faults that are difficult to detect by the residual chi-square test. To address the limitation of the SPRT in accurately determining the end time of faults, an improved SPRT is proposed. The improved SPRT reduces the influence of historical fault on the fault statistics by introducing forgetting factors to improve its sensitivity to the fault end. The simulation experiment indicates that the proposed method can quickly detect and isolate abrupt and ramp faults, and promptly restore normal operation of the integrated navigation system after the fault ends, effectively improving the fault tolerance and reliability of the integrated navigation system.
ABSTRACT
Immune checkpoint inhibitors (ICIs) have made significant breakthroughs in the treatment of a variety of malignancies. As its use increases, the unique immune-mediated toxicity profile of ICls are becoming apparent. We report a case of immune-related endocrine adverse events (irAE) in a patient with hepatocellular carcinoma treated with anti-programmed cell death protein 1 (PD-1) (tislelizumab). Although many irAEs have been reported, few cases of severe thyrotoxicosis have been described after immunotherapy in the literature. We present the case of a 49-year-old male who experienced a Grade 3 tislelizumab-related adverse reaction according to Common Terminology Criteria for Adverse Events (CTCAE5.0) and received methylprednisolone, thiamazole, and levothyroxine sodium tablets. Early identification of irAEs, risk factors, regular monitoring, use of steroids and/or immunoglobulins, and adjuvant supportive care are critical to the clinical prognosis of patients. It should be underlined that the tumor benefits of ICI therapy outweigh the risks associated with ICI-induced endocrine disorders, and ICI treatment should not be stopped or delayed except in rare cases (adrenal crisis, severe thyrotoxicosis). The familiarity of healthcare professionals with irAEs of the thyroid when thyrotoxicosis occurs is important to facilitate an effective diagnosis and appropriate treatment of this increasingly common thyroid disorder.
ABSTRACT
Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe. We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.
ABSTRACT
To comprehensively understand antibiotic resistant genes (ARGs) profile in the subtropical drinking water river-reservoir system, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate the spatial-temporal characteristics of ARGs diversity, bacterial host and resistance mechanism, and to analyze the key environmental factors driving ARGs profile variation. The results indicated that a total of 440 ARGs were detected in the target system, and the ARGs distribution pattern in the reservoir was attributed to autologous evolution or the comprehensive influence of feeding river system. The predominant bacterial host at different sites showed similar variations to dominated ARGs, and Proteobacteria, Actinobacteria and Bacteroidetes harbored most ARGs at phylum level, which showed the highest proportions of 74%, 37% and 35%, respectively. Antibiotic efflux was the primary resistance mechanism in all samples from wet season (45%-60%), yet the samples from dry season exhibited multiple resistance mechanisms, including inactivation (37%-52%), efflux (44%), and target alteration (43%). The total relative abundances of ARGs in the target system ranged from 0.89 × 10-2 to 1.71 × 10-2, and seasonal variation had a more significant influence on ARGs abundance than spatial variation (R = 0.68, P < 0.01). Environmental factors analysis indicated that the concentrations of nitrite nitrogen and total organic carbon were significant factors explaining ARGs number and various resistance mechanism proportions (P < 0.01), accounting for 48.7% and 61.1% of the variation, respectively; ammonia nitrogen concentration, total organic carbon concentration, temperature and pH were the significant influence factors on the relative abundance of ARGs (P < 0.05), with standardized regression weights of 0.700, 1.414, 1.447, and 1.727, respectively. In summary, in the surface water of the target system, ARGs diversity was primarily driven by ARGs horizontal transfer and antibiotics biosynthesis. Nutrients mainly promoted ARGs abundance by providing abundant energy, rather than increasing bacterial reproductive capacity.
Subject(s)
Drinking Water , Genes, Bacterial , Rivers , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Bacteria/genetics , Carbon , NitrogenABSTRACT
Solid acid catalysts with bi-acidity are promising as workhouse catalysts in biorefining to produce high-quality chemicals and fuels. Herein, we report a new strategy to develop bi-acidic cascade catalysts by separating both acid sites in geometry via the atomic layer deposition (ALD) of Lewis acidic alumina on Brønsted acidic supports. Visualized by transmission electron microscopy and electron energy loss spectroscopy mapping, the ALD-deposited alumina forms a conformal alumina domain with a thickness of around 3 nm on the outermost surface of mesoporous silica-alumina. Solid state nuclear magnetic resonance investigation shows that the dominant Lewis acid sites distribute on the outermost surface, whereas intrinsic Brønsted acid sites locate inside the nanopores within the silica-rich substrate. In comparison to other bi-acidic solid catalyst counterparts, the special geometric distance of Lewis and Brønsted acid sites minimized the synergetic effect, leading to a cascade reaction environment. For cascade glucose conversion, the designed ALD catalyst showed a highly enhanced catalytic performance.
ABSTRACT
To understand the dynamics of planktonic microbial community and its metabolism processes in subtropical drinking water river-reservoir system with lower man-made pollution loading, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate spatial-temporal characteristics of community profile and functional genes involved in biological metabolism, and to analyze the influence of environmental factors. The results indicated that Proteobacteria and Actinobacteria were the most diverse phyla with proportion ranges of 9%-80% in target system, and carbohydrate metabolism (5.76-7.12 × 10-2), amino acid metabolism (5.78-7.21 × 10-2) and energy metabolism (4.07-5.17 × 10-2) were found to be the dominant pathways of biological metabolism. Although there were variations in biological properties both spatially and temporally, seasonal variation had a greater influence on microbial community and biological metabolism, than locational differences. Regarding the role of environmental factors, this study revealed that microbial diversity could be affected by multiple abiotic factors, with total organic carbon, total phosphorus and temperature being more influential (absolute value of standardized regression weights >2.13). Stochastic processes dominated the microbial community assembly (R2 of neutral community model = 0.645), while niche-based processes differences represented by nutrients, temperature and pH level played secondary roles (R > 0.388, P < 0.01). Notably, the synergistic influences among the environmental factors accounted for the higher percentages of community variation (maximum proportion up to 17.6%). Additionally, pH level, temperature, and concentrations of dissolved oxygen, carbon and nitrogen were found to be the significant factors affecting carbon metabolism pathways (P < 0.05), yet only total organic carbon significantly affected on nitrogen transformation (P < 0.05). In summary, the microbial profile in reservoir is not completely dominated by that in feeding river, and planktonic microbial community and its metabolism in subtropical drinking water river-reservoir system are shaped by multiple abiotic and biotic factors with underlying interactions.
ABSTRACT
The use of small agonists to target stimulators of interferon genes (STING) has been demonstrated to be a promising strategy for the treatment of various cancers and infectious diseases. Herein, we discovered a series of 1H-pyrrole-3-carbonitrile derivatives as potential STING agonists. On this basis, the structure-activity relationship of this scaffold was studied by introducing various substituents on the aniline ring system. Representative compounds 7F, 7P, and 7R all displayed comparable activities to the reported STING agonist SR-717 in binding various hSTING alleles and induced reporter signal in human THP1 cell lines. Model compound 7F induced phosphorylation of TBK1, IRF3, p65, and STAT3 in a STING-dependent fashion and stimulated the expression of target genes IFNB1, CXCL10, and IL6 in a time-dependent manner in human THP1 cells. Our findings afforded a series of novel STING agonists with promising potential.
ABSTRACT
BACKGROUND: This study developed an intelligent, pH-sensitive and amine-responsive colorimetric label based on chitosan, whey protein and thymol blue by controlling the pH value of the film-forming solution. The obtained label was used to monitor shrimp freshness in real time. The results of this study offer a new approach for developing highly intelligent biogenic labels for freshness monitoring during seafood preservation and processing. RESULTS: The pH 2.0 chitosan-whey protein-thymol blue (CWT-pH 2.0) label exhibited remarkable properties, including the highest tensile strength (5.90 MPa), excellent thermal stability, low water solubility (27.80%) and highly sensitive color responsiveness. The characterization techniques of scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy confirmed the effective immobilization of thymol blue within the film-forming matrix through hydrogen bonding. Furthermore, the CWT-pH 2.0 label demonstrated visible color changes in the presence of volatile ammonia concentrations ranging from 25 to 25 000 ppm. Consequently, the label successfully facilitated real-time monitoring of shrimp freshness during storage at 4 °C. Importantly, the release rate of thymol blue from the label in food simulants was minimal, measuring only 2.53%. CONCLUSION: The CWT-pH 2.0 label exhibits significant potential as a highly intelligent biogenic label for freshness monitoring in seafood preservation and processing. © 2023 Society of Chemical Industry.
Subject(s)
Chitosan , Chitosan/chemistry , Amines , Whey Proteins , Seafood/analysis , Hydrogen-Ion Concentration , Anthocyanins/chemistry , Food Packaging/methodsABSTRACT
Carbapenem-resistant (CR) Klebsiella oxytoca complex can be associated with high mortality, emerging as a new threat to the public health. K. oxytoca complex is phylogenetically close to K. pneumoniae, one of most common species associated with multidrug resistance in Enterobacterale. The latest research showed that K. oxytoca is a complex of six species. Currently, the epidemiological and genomic characteristics of CR K. oxytoca complex in China are still unclear. Here, we conducted a multi-center study on 25 CR K. oxytoca complex collected from five representative regions in China. These isolates were, respectively, recovered from respiratory tract (12 cases, 48.0%), abdominal cavity (5 cases, 20.0%), blood (4 cases, 16.0%), urine tract (3 cases, 12.0%) and skin or soft tissue (1 cases, 4.0%). Among them, 32.0% (8/25) of patients infected with K. oxytoca complex had a poor prognosis. In this study, three K. oxytoca complex species were detected, namely K. michiganensis, K. oxytoca and K. pasteurii, among which K. michiganensis was the most common. Three carbapenemase genes were identified, including blaNDM-1 (10, 38.5%), blaKPC-2 (9, 34.6%) and blaIMP (6 blaIMP-4 and 1 blaIMP-8; 7, 26.9%). Subsequent multilocus sequence typing identified various sequence types (STs), among which ST43, ST92 and ST145 were relatively common. Different from the clonal dissemination of high-risk carbapenem-resistant K. pneumoniae strains, our research revealed a polyclonal dissemination characteristic of CR K. oxytoca complex in China. S1-nuclease PFGE and Southern blot experiment showed that carbapenemase genes were encoded in plasmids of different sizes. Two blaNDM-harboring plasmids were subsequently sequenced, and were characterized to be IncX3 and IncC incompatibility groups, respectively. This is the first multi-center study of CR K. oxytoca complex in China, which improved our understanding of the prevalence and antimicrobial resistance characteristics of CR K. oxytoca complex in China.
ABSTRACT
Colistin has been considered a last-line option for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Heterogeneous resistance to colistin leads to unexplained clinical colistin treatment failure for CRKP. Our study aimed to investigate the extent of colistin heteroresistance among CRKP strains in China. A total of 455 colistin-susceptible strains, collected from six tertiary care hospitals in China, were characterized. The overall rate of colistin heteroresistance was 6.2%, as determined by the population analysis profiles (PAPs). Genomic analysis revealed that 60.7% of the colistin-heteroresistant isolates belonged to the epidemic sequence type 11 (ST11) clone. Single-nucleotide polymorphisms (SNPs) suggested that 6 ST5216 strains shared the same origin. Each of the subpopulations had a ≥8-fold decrease in colistin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), which indicated that heteroresistance could be suppressed by an efflux pump inhibitor. In addition, our results suggested that the PhoPQ pathway plays an important role in the mechanisms of heteroresistance. IMPORTANCE The problem of CRKP has raised alarms concerning global health. Our study enriches the epidemiological study of colistin heteroresistance among CRKP strains in China, where the prevalence of this phenomenon was previously unknown. Importantly, colistin-heteroresistant strains may cause the failure of clinical treatment with colistin, even if the clinical laboratory reports that the strains are sensitive. The commonly used broth microdilution method is unable to detect this special phenomenon. Additionally, our results indicate that efflux pumps play a major role in colistin heteroresistance, and inhibitors can effectively reverse it. Our study is the first to provide a detailed analysis of the prevalence of colistin heteroresistance in China, as well as an analysis of the genetic mechanisms of this phenomenon.