ABSTRACT
Coal type identification is the basic work of coal quality inspection, which is of great significance to the normal operation of power generation, metallurgy, and other industries. The traditional coal-type identification method is complicated and requires comprehensive determination of various chemical parameters to obtain more accurate analysis results. Hyperspectral detection and analysis technology has the advantages of being simple, fast, nondestructive, and safe, and is widely used in a variety of fields. In this study, typical spectral feature parameters of coal samples were extracted based on hyperspectral data, and the parameters' sensitivity to coal types was explored using one-way ANOVA. The results showed that the coal spectral feature parameters of DI1-2µm and AD2.2µm significantly differed with coal species, indicating that the two parameters were class-sensitive features. When DI1-2µm and AD2.2µm were used to construct the Fisher discriminant model, the coal types could be discriminated with high accuracy. At the same time, the correlation between the extracted spectral feature parameters and the physicochemical parameters of bituminous coal and anthracite was analyzed. The results showed that there was a certain basis for using the extracted spectral feature parameters as the sensitive spectral characteristics of the model, and the application potential of the spectral characteristics of coal in the nondestructive prediction analysis of coal parameters was further discussed.
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Ecological restoration is imperative for controlling desertification. Potential natural vegetation (PNV), the theoretical vegetation succession state, can guides near-natural restoration. Although a rising transition from traditional statistical methods to advanced machine learning and deep learning is observed in PNV simulation, a comprehensive comparison of their performance is still unexplored. Therefore, we overview the performance of PNV mapping in terms of 12 commonly used methods with varying spatial scales and sample sizes. Our findings indicate that the methodology should be carefully selected due to the variation in performance of different model types, with Area Under the Curve (AUC) values ranging from 0.65 to 0.95 for models with sample sizes up to 80% of the total sample size. Specifically, semi-supervised learning performs best with small sample sizes (i.e., 10 to 200), while Random Forest, XGBoost, and artificial neural networks perform better with large sample sizes (i.e., over 500). Further, the performance of all models tends to improve significantly as the sample size increases and the grain size of the crystals becomes smaller. Take the downstream Tarim River Basin, a hyper-arid region undergoing ecological restoration, as a case study. We showed that its potential restored areas were overestimated by 2-3 fold as the spatial scale became coarser, revealing the caution needed while planning restoration projects at coarse resolution. These findings enhance the application of PNV in the design of restoration programs to prevent desertification.
Subject(s)
Conservation of Natural Resources , Neural Networks, Computer , Ecosystem , Ecology , Machine Learning , Plants , Models, TheoreticalABSTRACT
Cyclic nucleic acids are biologically stable against nucleic acid exonucleases due to the absence of 5' and 3' termini. Studies of cyclic nucleic acids mainly focus on cyclic single-stranded nucleic acids. Cyclic single-stranded nucleic acids are further divided into circular RNA (circRNA) and circular single-stranded DNA (cssDNA). The synthesis methods of circRNA include lasso-driven cyclization, intron-paired cyclization, intron cyclization, intron complementary pairing-driven cyclization, RNA-binding protein-driven cyclization, and artificial synthesis depending on the source. Its main role is to participate in gene expression and the treatment of some diseases. Circular single-stranded DNA is mainly synthesized by chemical ligation, template-directed enzyme ligation, and new techniques for the efficient preparation of DNA single loops and topologies based on CircLigase. It is mainly used in rolling circle amplification (RCA) technology and in the bioprotection of circular aptamers and second messengers. This review focuses on the types, synthesis methods, and applications of cyclic single-stranded nucleic acids, providing a reference for further research on cyclic single-stranded nucleic acids.
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BACKGROUND AND PURPOSE: GLP-1 receptor agonists are clinically utilized for type 2 diabetes and obesity. In vitro and in vivo preclinical studies were performed to assess the druggability of a novel small molecule GLP-1 receptor biased agonist SAL0112. EXPERIMENTAL APPROACH: The HTRF assay, FLIPR assay, TR-FRET assay, and PathHunter assay were utilized for in vitro studies. Liver transporter tests were conducted using the HEK293-OATP1B1 and HEK293-OATP1B3 cell lines. In vitro stability assessments of various species and in vivo PK studies in rodents were performed. A model of type 2 diabetes and obesity induced by a high-energy diet in transgenic C57BL/6 mice expressing the human GLP-1 receptor gene was conducted. PRINCIPAL RESULTS: SAL0112 demonstrated high potency and selectivity in activating the Gαs pathway of the GLP-1 receptor, with no observed desensitization. SAL0112 demonstrated greater stability in human and rat liver microsomes compared to Danuglipron. In vivo PK studies revealed higher absorption of SAL0112 in rats. SAL0112 displayed a significantly lower potential for DDI on liver transporters compared to Danuglipron. SAL0112 led to significant reductions in body weight (P<0.001), blood glucose levels in OGTT (P<0.001), HbA1c (P<0.05) and improved insulin resistance (P<0.01). Notably, it increased peripheral adipocyte density and resolved hepatic steatosis. The efficacy of SAL0112 was found to be comparable to that of Danuglipron and Liraglutide. CONCLUSION: SAL0112 demonstrated potent and selective GLP-1 receptor biased agonism, effectively alleviating signs of type 2 diabetes in a mouse model. These promising findings pave the way for the advancement of SAL0112 into clinical trials.
Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Mice, Inbred C57BL , Animals , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Humans , Male , Rats , HEK293 Cells , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/blood , Mice , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/pharmacokinetics , Mice, Transgenic , Obesity/drug therapy , Obesity/metabolism , Microsomes, Liver/metabolism , Rats, Sprague-Dawley , Blood Glucose/drug effects , Blood Glucose/metabolismABSTRACT
Pseudomonas aeruginosa is one of the leading causes of nosocomial infections worldwide and has emerged as a serious public health threat, due in large part to its multiple virulence factors and remarkable resistance capabilities. Stk1, a eukaryotic-type Ser/Thr protein kinase, has been shown in our previous work to be involved in the regulation of several signalling pathways and biological processes. Here, we demonstrate that deletion of stk1 leads to alterations in several virulence- and resistance-related physiological functions, including reduced pyocyanin and pyoverdine production, attenuated twitching motility, and enhanced biofilm production, extracellular polysaccharide secretion, and antibiotic resistance. Moreover, we identified AlgR, an important transcriptional regulator, as a substrate for Stk1, with its phosphorylation at the Ser143 site catalysed by Stk1. Intriguingly, both the deletion of stk1 and the mutation of Ser143 of AlgR to Ala result in similar changes in the above-mentioned physiological functions. Furthermore, assays of algR expression in these strains suggest that changes in the phosphorylation state of AlgR, rather than its expression level, underlie changes in these physiological functions. These findings uncover Stk1-mediated phosphorylation of AlgR as an important mechanism for regulating virulence and resistance in P. aeruginosa.
Subject(s)
Bacterial Proteins , Gene Expression Regulation, Bacterial , Protein Serine-Threonine Kinases , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/pathogenicity , Pseudomonas aeruginosa/enzymology , Phosphorylation , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Virulence , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Virulence Factors/genetics , Virulence Factors/metabolism , Biofilms/growth & development , Transcription Factors/genetics , Transcription Factors/metabolism , Drug Resistance, Bacterial/genetics , Pseudomonas Infections/microbiology , Trans-ActivatorsABSTRACT
BACKGROUND: Very and extremely preterm infants (VEPIs) experience sensory deprivation in the neonatal intensive care unit (NICU). While various sensory-supported interventions might improve immediate physiological response, their impact on long-term development remains unclear. Additionally, these interventions may pose challenges in the NICU environment due to complex treatments and monitoring requirements. AIMS: This review aimed to understand the current evidence on sensory-supported interventions in the NICU, identify the components of these interventions and determine their effects on the VEPIs. STUDY DESIGN: A systematic search across nine electronic databases (PubMed, EBSCO, EMBASE, Web of Science, Scopus, Cochrane, Cochrane trial, IEEE Xplore DL and ACM DL) was conducted in December 2020 and updated in September 2022. The search gathers information on sensory-supported interventions for VEPIs in the NICU. RESULTS: The search yielded 23 systematic reviews and 22 interventional studies, categorized into auditory (19), tactile/kinesthetic (5), positional/movement support (7), visual (1) and multisensory (13) interventions. While unimodal and multimodal interventions showed short-term benefits, their long-term effects on VEPIs are indeterminate. Translating these findings into clinical practice remains a challenge due to identified gaps. CONCLUSION: Our reviews indicate that sensory-supported interventions have a transient impact, with intervention studies reporting positive effects. Future research should develop and test comprehensive, continuous multisensory interventions tailored for the early NICU stage. RELEVANCE TO CLINICAL PRACTICE: Multimodal sensory interventions show promise for VEPIs, but long-term effects need further study. Standardizing protocols for NICU integration and parental involvement is crucial. Ongoing research and collaboration are essential for optimizing interventions and personalized care.
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Objective: Molidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear. Methods: We searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia. Results: Six studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P < 0.00001] and ΔHb was also significantly higher for molidustat than for ESAs [MD = 0.25 (95 % CI 0.09 to 0.40), P = 0.002]. For NDD patients, Δhepcidin was significantly lower for molidustat than for placebo [MD = -20.66 (95 % CI: -31.67 to -9.66), P = 0.0002] and Δhepcidin was also significantly lower for molidustat than for ESAs [MD = -24.51 (95 % CI: -29.12 to -19.90), P < 0.00001]. For NDD patients, Δiron was significantly lower for molidustat than for ESAs [MD = -11.85 (95 % CI: -15.52 to -8.18), P < 0.00001], and ΔTSAT was also significantly lower for molidustat than for ESAs [MD = -5.29 (95 % CI: -6.81 to -3.78), P < 0.00001]. For NDD patients, Δferritin was significantly lower for molidustat than for placebo [MD = -90.01 (95 % CI: -134.77 to -45.25), P < 0.00001]. However, for DD-CKD patients, molidustat showed an effect similar to that of ESAs on increasing the Hb level [MD = -0.18 (95 % CI: -0.47 to 0.11), P = 0.23], Δiron level [MD = 3.78 (95 % CI: -7.21 to 14.76), P = 0.5], Δferritin level [MD = 25.03 (95 % CI: -34.69 to 84.75), P = 0.41], and Δhepcidin level [MD = 1.20 (95 % CI: -4.36 to 6.76), P = 0.67]. For DD-CKD patients, compared with the placebo or ESA group, molidustat showed a significantly higher level on ΔTSAT[MD = 3.88 (95 % CI: 2.10 to 5.65), P < 0.0001] and a slightly increased level on ΔTIBC level [MD = 1.08 (95 % CI: -0.07 to 2.23), P = 0.07]. There was no significant difference in the incidence of severe adverse events (SAEs), death, and cardio-related adverse events between molidustat and the ESAs groups. Conclusions: Moricizine can effectively improves Hb levels in NDD patients and corrects anemia in DD patients without increasing adverse event incidence.
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Chemical constituents of 70% ethanol extract of Alangium chinense subsp. pauciflorum were investigated. The 70% ethanol extract of A. chinense subsp. pauciflorum was isolated and purified by D-101 macroporous resins, silica gel, Sephadex LH-20 and other methods. As a result, nineteen compounds were isolated and identified as 4-cyclohexene-1α,2α,3α-triol-1-O-ß-D-glucoside(1), 1ß,4α,6α,13-tetrahydroxy-eudesm-11(12)-ene(2), sucrose(3), 1'-O-benzyl-α-L-rhamnopyranosyl-(1â³â6')-ß-D-glucopyranoside(4), bis(2-ethylhexyl)benzene-1,2-dicarboxylate(5),(Z)-10-heneicosenoic acid(6), di-O-methylcrenati(7), methyl-α-D-fructofuranoside(8), ß-daucosterol(9), syringic acid(10), vanillicacid(11), octacosanol(12), isoarborinol(13), 2,7-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthalenecarboxylate(14),vanillin(15), coniferyl aldehyde(16), 9(11)-dehydroergosterolperoxide(17), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3ß-ol(18), ß-sitosterol(19), respectively. Compounds 1 and 2 were new compounds, compounds 5-11, 13, 15-18 were isolated from Alangium for the first time.The anti-inflammatory activity of compourd 1 was determinded by the LPS-induced RAW264.7 macrophage inflammation model. The results showed that the new compound 1 has a certain inhibitory effect on LPS-induced NO production of RAW264.7 cells, and the inhibitory rate was 54.57%.
Subject(s)
Alangiaceae , Lipopolysaccharides , Anti-Inflammatory Agents/pharmacology , Ethanol , Plant ExtractsABSTRACT
The chemical composition of the aqueous part of the extract from Lindera aggregata was studied, which was separated and purified by the macroporous resin column chromatography, MCI medium pressure column chromatography, semi-preparative high-performance liquid phase and other methods. The structures of the compounds were identified according to physical and chemical properties and spectroscopic data. Thirteen compounds were isolated and identified from the aqueous extracts, which were identified as(1S,3R,5R,6R,8S,10S)-epi-lindenanolide H(1), tachioside(2), lindenanolide H(3), leonuriside A(4), 3,4-dihydroxyphenyl ethyl ß-D-glucopyranoside(5), 3,4,5-trimethoxyphenol-1-O-6-α-L-rhamnose-(1â6)-O-ß-D-glucoside(6), 5-hydroxymethylfurfural(7),(+)-lyoniresin-4-yl-ß-D-glucopyranoside(8), lyoniside(9), norboldine(10), norisopordine(11), boldine(12), reticuline(13). Among them, compound 1 was a new one, and compounds 2, 5, 6, 8, 9 were obtained from L. aggregata for the first time. The inflammatory model was induced by lipopolysaccharide(LPS) in the RAW264.7 cells. The results showed that compounds 1, 8, 10 and 12 had significant anti-inflammatory activity.
Subject(s)
Lindera , Sesquiterpenes , Lindera/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , GlucosidesABSTRACT
Bacillus amyloliquefaciens is a well-accepted probiotic, with many benefits for both humans and animals. The ability of intestinal stem cells (ISCs) to develop into several intestinal epithelial cell types helps accelerate intestinal epithelial regeneration. Limited knowledge exists on how bacteria regulated ISCs proliferation and regeneration. Our study investigated the effects of Bacillus amyloliquefaciens supplementation on ISC proliferation and regeneration and intestinal mucosal barrier functions in piglets exposed to lipopolysaccharide (LPS). Eighteen piglets (male, 21 days old) were randomly split into 3 clusters: CON cluster, LPS cluster, and SC06+LPS cluster. On day 21, 100 µg/kg body weight of LPS was intraperitoneally administered to the SC06+LPS and LPS groups. We found SC06 supplementation maintained the intestinal barrier integrity, enhanced intestinal antioxidant capacity, reduced generation of inflammatory response, and suppressed enterocyte apoptosis against the deleterious effects triggered by LPS. In addition, our research indicated that the SC06 supplementation not only improved the ISC regeneration, but also resulted in upregulation of aryl hydrocarbon receptor (AhR) in LPS-challenge piglets. Further studies showed that SC06 also induced ISC differentiation toward goblet cells and inhibited their differentiation to intestinal absorptive cells and enterocytes. The coculture system of SC06 and ileum organoids revealed that SC06 increased the growth of ISCs and repaired LPS-induced organoid damage through activating the AhR/STAT3 signaling pathway. These findings showed that SC06, possibly through the AhR/STAT3 pathway, accelerated ISC proliferation and promoted epithelial barrier healing, providing a potential clinical treatment for IBD. Our research demonstrated that SC06 is effective in preventing intestinal epithelial damage after pathological injury, restoring intestinal homeostasis, and maintaining intestinal epithelial regeneration.
Subject(s)
Bacillus amyloliquefaciens , Lipopolysaccharides , Humans , Male , Animals , Swine , Lipopolysaccharides/pharmacology , Intestinal Mucosa/metabolism , Bacillus amyloliquefaciens/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Stem Cells/metabolism , Cell Proliferation , Inflammation/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
Vaccination has significantly reduced the incidence of invasive infections caused by several bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. However, no vaccines are available for many other invasive pathogens. A major hurdle in vaccine development is the lack of functional markers to quantify vaccine immunity in eliminating pathogens during the process of infection. Based on our recent discovery of the liver as the major organ of vaccine-induced clearance of blood-borne virulent bacteria, we here describe a new vaccine evaluation system that quantitatively characterizes the key features of effective vaccines in shuffling virulent bacteria from the blood circulation to the liver resident macrophage Kupffer cells (KCs) and sinusoidal endothelial cells (LSECs) in mouse septic infection model. This system consists of three related correlates or assays: pathogen clearance from the bloodstream, pathogen trapping in the liver, and pathogen capture by KCs/LSECs. These readouts were consistently associated with the serotype-specific immunoprotection levels of the 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against lethal infection of S. pneumoniae, a major invasive Gram-positive pathogen of community-acquired infections in humans. Furthermore, the reliability and sensitivity of these correlates in reflecting vaccine efficacy were verified with whole cell vaccines of Klebsiella pneumoniae and Escherichia coli, two major Gram-negative pathogens in hospital-acquired invasive infections. This system may be used as effective readouts to evaluate the immunoprotective potential of vaccine candidates in the preclinical phase by filling the current technical gap in vaccine evaluation between the conventional in vitro approaches (e.g. antibody production and pathogen neutralization/opsonophagocytosis) and survival of immunized animals.
Subject(s)
Cross Infection , Pneumococcal Infections , Humans , Animals , Mice , Endothelial Cells , Reproducibility of Results , Streptococcus pneumoniae , Pneumococcal Vaccines , Vaccination , Serogroup , Vaccines, Conjugate , Pneumococcal Infections/epidemiologyABSTRACT
BACKGROUND & AIMS: Necroptosis, a novel type of programmed cell death, is intricately associated with inflammatory response. Currently, most studies focus on the activation of necroptosis, while the mechanisms underlying the negative regulation of necroptosis remain poorly understood. METHODS: The effects of sestrin2 (SESN2) overexpression or knockdown on the regulation of necroptosis were assessed in the TNFα/Smac-mimetic/Z-VAD-FMK (T/S/Z)-induced necroptosis model and palmitic acid (PA)-induced lipotoxicity model. Western-blot, co-Immunoprecipitation, Glutathione S-transferase pull-down, and confocal assays were employed to explore the regulatory mechanisms including protein-protein interactions and post-translational modification. Furthermore, we used GSK'872, a specific inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK) 3, to evaluate the relationship between SESN2-related alterations and RIPK3-mediated necroptosis in T/S/Z-induced necroptosis model, PA-induced lipotoxicity model, and high-fat high-cholesterol diet (HFHCD)-induced non-alcoholic steatohepatitis model. RESULTS: Our findings revealed that SESN2 was upregulated under conditions that induce necroptosis and functioned as a negative regulator of necroptosis. High levels of SESN2 could equipped hepatocytes with the ability to defend against necroptotic inflammation and oxidative stress. Mechanistically, SESN2 interacted with RIPK3 and tuned down necroptosis by inhibiting the phosphorylation of RIPK3, promoting the ubiquitination of RIPK3, and preventing the formation of the RIPK1/RIPK3 necrosome. The depletion of SESN2 resulted in excessive necroptosis, accompanied by increased fat accumulation, inflammation, and oxidative stress in the experimental steatohepatitis model. Blocking necroptosis by GSK'872 reduced the liberation of pro-inflammatory cytokines and reactive oxygen species generation, but not hepatocyte fat deposition, in both PA-treated SESN2 knockout cells and HFHCD-fed SESN2 knockout mice, suggesting that the activation of RIPK3-mediated necroptosis may partially account for the hyperinflammation and excessive oxidative stress induced by SESN2 deficiency. CONCLUSION: Our results suggested that SESN2 inhibited RIPK3-mediated necroptosis; this regulation is an important for the immune homeostasis and the redox balance in the liver.
Subject(s)
Fatty Liver , Necroptosis , Animals , Mice , Homeostasis , Inflammation/metabolism , Necrosis , Oxidation-Reduction , Protein Serine-Threonine Kinases/metabolismABSTRACT
The methodology of sugaring out-assisted liquid-liquid extraction (SULLE) coupled with high-performance liquid chromatography-fluorescence detection was devised for quantifying bisphenol A (BPA) and bisphenol B (BPB) in beeswax. The effectiveness of SULLE was methodically explored and proved superior to the salting out-assisted liquid-liquid extraction approach for beeswax sample preparation. The analytical performance underwent comprehensive validation, revealing detection limits of 10 µg/kg for BPA and 20 µg/kg for BPB. The method developed was employed to analyse commercial beeswax (n = 15), beeswax foundation (n = 15) and wild-build comb wax (n = 26) samples. The analysis revealed BPA presence in four commercial beeswax samples and three beeswax foundation samples, with the highest detected residue content being 88 ± 7 µg/kg. For BPB, two beeswax foundation samples were positive, with concentrations below the limits of quantification and 85 ± 4 µg/kg, respectively. No bisphenols were detected in wild-build comb wax. Furthermore, the bisphenol removal efficacy of two recycling methods-boiling in water and methanol extraction-was assessed. The findings indicated that after four recycling cycles using water boiling, 9.6% of BPA and 29.2% of BPB remained in the beeswax. Whereas methanol extraction resulted in approximately 7% residual after one recycling process. A long-term study over 210 days revealed the slow degradation of bisphenols in comb beeswax. This degradation fitted well with a first-order model, indicating half-lives (DT50) of 139 days for BPA and 151 days for BPB, respectively. This research provides the first report on bisphenol contamination in beeswax. The low removal rate during the recycling process and the gradual degradation in beeswax underscore the significance of bisphenol contamination and migration in bee hives along with their potential risk to pollinators warranting concern. Furthermore, the developed SULLE method shows promise in preparing beeswax samples to analyse other analytes.
Subject(s)
Methanol , Phenols , Sugars , Waxes , Animals , Bees , Methanol/analysis , Chromatography, High Pressure Liquid , Benzhydryl Compounds/analysis , Liquid-Liquid Extraction , Water/analysisABSTRACT
Given that combination with multiple biomarkers may well raise the predictive value of wound age, it appears critically essential to identify new features under the limited cost. For this purpose, the present study explored whether the gene expression ratios provide unique time information as an additional indicator for wound age estimation not requiring the detection of new biomarkers and allowing full use of the available data. The expression levels of four wound-healing genes (Arid5a, Ier3, Stom, and Lcp1) were detected by real-time polymerase chain reaction, and a total of six expression ratios were calculated among these four genes. The results showed that the expression levels of four genes and six ratios of expression changed time-dependent during wound repair. The six expression ratios provided additional temporal information, distinct from the four genes analyzed separately by principal component analysis. The overall performance metrics for cross-validation and external validation of four typical prediction models were improved when six ratios of expression were added as additional input variables. Overall, expression ratios among genes provide temporal information and have excellent potential as predictive markers for wound age estimation. Combining the expression levels of genes with ratio-expression of genes may allow for more accurate estimates of the time of injury.
Subject(s)
Contusions , Rats , Animals , Humans , Rats, Sprague-Dawley , Contusions/genetics , Contusions/metabolism , Muscle, Skeletal/metabolism , Wound Healing/genetics , Biomarkers/metabolismABSTRACT
A widely applied pesticide of azoxystrobin, is increasingly detected in the water environment. Concern has been raised against its potential detriment to aquatic ecosystems. It has been shown that exposure to azoxystrobin interfere with the locomotor behavior of zebrafish larvae. This study aims to investigate whether exposure to environmental levels of azoxystrobin (2 µg/L, 20 µg/L, and 200 µg/L) changes the behavior of male adult zebrafish. Herein, we evaluated behavioral response (locomotor, anxiety-like, and exploratory behaviors), histopathology, biochemical indicators, and gene expression in male adult zebrafish upon azoxystrobin exposure. The study showed that exposure to azoxystrobin for 42 days remarkably increased the locomotor ability of male zebrafish, resulted in anxiety-like behavior, and inhibited exploratory behavior. After treatment with 200 µg/L azoxystrobin, vasodilatation, and congestion were observed in male zebrafish brains. Exposure to 200 µg/L azoxystrobin notably elevated ROS level, MDA concentration, CAT activity, and AChE activity, while inhibiting SOD activity, GPx activity, ACh concentration, and DA concentration in male zebrafish brains. Moreover, the expression levels of genes related to the antioxidant, cholinergic, and dopaminergic systems were significantly changed. This suggests that azoxystrobin may interfere with the homeostasis of neurotransmitters by causing oxidative stress in male zebrafish brains, thus affecting the behavioral response of male zebrafish.
Subject(s)
Pyrimidines , Strobilurins , Water Pollutants, Chemical , Zebrafish , Animals , Male , Zebrafish/metabolism , Ecosystem , Oxidative Stress , Cholinergic Agents/metabolism , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolismABSTRACT
Narrowband emissive multiple resonance (MR) emitters promise high efficiency and stability in deep-blue organic light-emitting diodes (OLEDs). However, the construction of ideal ultra-narrow-band deep-blue MR emitters still faces formidable challenges, especially in balancing bathochromic-shift emission, spectral narrowing, and aggregation suppression. Here, DICz is chosen, which possesses the smallest full-width-at-half-maximum (FWHM) in MR structures, as the core and solved the above issue by tuning its peripheral substitution sites. The 1-substituted molecule Cz-DICz is able to show a bright deep-blue emission with a peak at 457 nm, an extremely small FWHM of 14 nm, and a CIE coordinate of (0.14, 0.08) in solution. The corresponding OLEDs exhibit high maximum external quantum efficiencies of 22.1%-25.6% and identical small FWHMs of 18 nm over the practical mass-production concentration range (1-4 wt.%). To the best of the knowledge, 14 and 18 nm are currently the smallest FWHM values for deep-blue MR emitters with similar emission maxima under photoluminescence and electroluminescence conditions, respectively. These discoveries will help drive the development of high-performance narrowband deep-blue emitters and bring about a revolution in OLED industry.
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Vaccination has substantially reduced the morbidity and mortality of bacterial diseases, but mechanisms of vaccine-elicited pathogen clearance remain largely undefined. We report that vaccine-elicited immunity against invasive bacteria mainly operates in the liver. In contrast to the current paradigm that migrating phagocytes execute vaccine-elicited immunity against blood-borne pathogens, we found that invasive bacteria are captured and killed in the liver of vaccinated host via various immune mechanisms that depend on the protective potency of the vaccine. Vaccines with relatively lower degrees of protection only activated liver-resident macrophage Kupffer cells (KCs) by inducing pathogen-binding immunoglobulin M (IgM) or low amounts of IgG. IgG-coated pathogens were directly captured by KCs via multiple IgG receptors FcγRs, whereas IgM-opsonized bacteria were indirectly bound to KCs via complement receptors of immunoglobulin superfamily (CRIg) and complement receptor 3 (CR3) after complement C3 activation at the bacterial surface. Conversely, the more potent vaccines engaged both KCs and liver sinusoidal endothelial cells by inducing higher titers of functional IgG antibodies. Endothelial cells (ECs) captured densely IgG-opsonized pathogens by the low-affinity IgG receptor FcγRIIB in a "zipper-like" manner and achieved bacterial killing predominantly in the extracellular milieu via an undefined mechanism. KC- and endothelial cell-based capture of antibody-opsonized bacteria also occurred in FcγR-humanized mice. These vaccine protection mechanisms in the liver not only provide a comprehensive explanation for vaccine-/antibody-boosted immunity against invasive bacteria but also may serve as in vivo functional readouts of vaccine efficacy.
Subject(s)
Kupffer Cells , Vaccines , Animals , Mice , Kupffer Cells/metabolism , Endothelial Cells , Macrophages/metabolism , Immunoglobulin G/metabolism , Liver , Antibodies, Viral/metabolism , Immunoglobulin M/metabolism , Receptors, IgG/metabolism , BacteriaABSTRACT
BANKGROUND: The tumor microenvironment (TME) is an internal environment composed of various cells and an extracellular matrix. Cancer stem cell-derived exosomes (CSC-Exos), as essential messengers involved in various tumor processes, are important carriers for bidirectional communication between the tumor microenvironment and tumor cells and play an important role in the tumor microenvironment. Nevertheless, few bibliometric analyses have been systematically studied in this field. METHODS: Therefore, we aimed to visualize the research hotspots and trends in this field through bibliometrics to comprehend the future evolution of fundamental and clinical research, as well as to offer insightful information and fresh viewpoints. The Scopus database was used to search the research literature related to exosomes and tumor microenvironments after the establishment of this repository. CiteSpace (version 5.8.R3) and VOSviewer (version 1.6.16) were used for visualization and analysis. RESULTS: In this study, a total of 2077 articles and reviews were included, with the number of articles on exosomes and tumor microenvironments significantly increasing yearly. Recent trends showed that the potential value of exosomes as "tumor diagnostics" and "the application prospect of exosomes as therapeutic agents and drug delivery carriers" will receive more attention in the future. CONCLUSIONS: We revealed the current status and hotspots of tumor stem cell-derived exosomes and tumor microenvironments globally through bibliometrics. The prospect of the regulatory role of CSC-Exos in TME, the potential value of diagnosis, and the application of drug delivery vectors will all remain cutting-edge research areas in the field of tumor therapy. Meanwhile, this study provided a functional literature analysis for related researchers.
Subject(s)
Exosomes , Neoplasms , Humans , Communication , Neoplastic Stem Cells , Tumor Microenvironment , BiologyABSTRACT
PURPOSE: To investigate whether the quality of skeletal muscle mass could predict short-term readmission in patients with hepatic encephalopathy (HE). METHOD: Patients with HE were enrolled from 2018 to 2022. Sarcopenia and myosteatosis were defined using the L3 skeletal muscle index (SMI) and skeletal muscle density (SMD) obtained from CT imaging. MELD-Sarcopenia score was calculated. Multivariable analysis and multiple linear regression were applied to identify predictors of 30-day readmission and length of hospitalization. RESULTS: 123 patients with HE were included. 55 (44.7%) and 87 (70.7%) patients were identified with sarcopenia and myosteatosis, respectively. Patients with sarcopenia exhibited a higher prevalence of myosteatosis, lower SMI and SMD (p < 0.05). Patients with myosteatosis were older, had a lower body mass index, a higher neutrophil-to-lymphocyte ratio and MELD-sarcopenia scores (p < 0.05). 10 (8.1%) patients were readmitted within 30 days. The readmitted group had a higher MELD-sarcopenia score (25.0 ± 6.6 vs. 19.5 ± 7.8, p = 0.034) and lower L3 SMD (28.3 ± 5.9 vs. 33.8 ± 6.9, p = 0.015). In the multivariable analysis, MELD-sarcopenia score (95% CI 1.388 [1.074-1.793], p = 0.012) and SMD (95% CI 0.778 [0.610-0.991], p = 0.042) were found to be significantly associated with the 30-day readmission of patients with HE. Age (p = 0.028), alcohol liver disease (p = 0.025), and hypertension (p = 0.003) were associated with the length of hospitalization for patients with HE. CONCLUSIONS: The MELD-sarcopenia score and SMD were identified as predictive factors for short-term readmission in patients diagnosed as HE.