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Determining the precise course of bacterial infection requires abundant in vivo real-time data. Synchronous monitoring of the bacterial load, temperature, and immune response can satisfy the shortage of real-time in vivo data. Here, we conducted a study in the joint-infected mouse model to synchronously monitor the bacterial load, temperature, and immune response using the second near-infrared (NIR-II) fluorescence imaging, infrared thermography, and immune response analysis for 2 weeks. Staphylococcus aureus (S. aureus) was proved successfully labeled with glucose-conjugated quantum dots in vitro and in subcutaneous-infected model. The bacterial load indicated by NIR-II fluorescence imaging underwent a sharp drop at 1 day postinfection. At the same time, the temperature gap detected through infrared thermography synchronously brought by infection reached lowest value. Meanwhile, the flow cytometry analysis demonstrated that immune response including macrophage, neutrophil, B lymphocyte, and T lymphocyte increased to the peak at 1 day postinfection. Moreover, both M1 macrophage and M2 macrophage in the blood have an obvious change at ~ 1 day postinfection, and the change was opposite. In summary, this study not only obtained real-time and long-time in vivo data on the bacterial load, temperature gap, and immune response in the mice model of S. aureus infection, but also found that 1 day postinfection was the key time point during immune response against S. aureus infection. Our study will contribute to synchronously and precisely studying the complicated complex dynamic relationship after bacterial infection at the animal level.
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This paper utilizes the theory of quantum diffusion to analyze the electron probability and spreading width of a wavepacket on each layer in a two-dimensional (2D) coupled system with edge disorder, aiming to clarify the effects of edge disorder on the stability of the electron periodic oscillations in 2D coupled systems. Using coupled 2D square lattices with edge disorder as an example, we show that, the electron probability and wavepacket spreading width exhibit periodic oscillations and damped oscillations, respectively, before and after the wavepacket reaches the boundary. Furthermore, these electron oscillations exhibit strong resistance against disorder perturbation with a longer decay time in the regime of large disorder, due to the combined influences of ordered and disordered site energies in the central and edge regions. Finally, we numerically verified the universality of the results through bilayer graphene, demonstrating that this anomalous quantum oscillatory behavior is independent of lattice geometry. Our findings are helpful in designing relevant quantum devices and understanding the influence of edge disorder on the stability of electron periodic oscillations in 2D coupled systems.
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INTRODUCTION: Alveolar echinococcosis (AE), caused by the larval forms of Echinococcus multilocularis, is a zoonotic disease affecting the liver, lungs, lymph nodes, kidneys, brain, bones, thyroid, and other organs. Diagnosing AE in a non-endemic area is usually challenging. With the rapid development and increasing application of sequencing techniques in recent years, metagenomic next-generation sequencing (mNGS) has become a powerful tool for diagnosing rare infectious diseases. CASE PRESENTATION: A 45-year-old woman was admitted to the hospital for the presence of pulmonary shadows for more than 3 months. The lung computed tomography (CT) at a local hospital revealed scattered solid and quasi-circular nodules in the left upper lobe, left lower lobe, right middle lobe, and right lower lobe. The largest nodule was located in the dorsal part of the right lung, measuring 2.0 × 1.7 × 1.5 cm. Moreover, abdominal CT revealed one space-occupying lesion each in the left and right lobes. The pathological analysis of the lung biopsy specimen revealed infiltration of lymphocytes, plasma cells, and eosinophils in the alveolar wall and interstitial area. No pathogenic bacteria were observed in the sputum smear and culture tests. There were no parasite eggs in the stool. The mNGS of the lung puncture tissue revealed 6156 sequence reads matching E. multilocularis; thus, the condition was diagnosed as AE. Albendazole 400 mg was administered twice daily, and the patient was stable during follow-up. CONCLUSION: This case emphasizes the role of mNGS in diagnosing AE. As a novel, sensitive, and accurate diagnostic method, mNGS could be an attractive approach for facilitating early diagnosis and prompt treatment of infectious diseases, especially when the infection was caused by rare pathogens.
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Equinococose , Echinococcus multilocularis , Sequenciamento de Nucleotídeos em Larga Escala , Pulmão , Metagenômica , Humanos , Feminino , Pessoa de Meia-Idade , Animais , Pulmão/parasitologia , Pulmão/patologia , Pulmão/diagnóstico por imagem , Metagenômica/métodos , Echinococcus multilocularis/genética , Echinococcus multilocularis/isolamento & purificação , Equinococose/diagnóstico , Equinococose/parasitologia , Tomografia Computadorizada por Raios X , Albendazol/uso terapêutico , Equinococose Pulmonar/diagnóstico , Equinococose Pulmonar/parasitologia , Equinococose Pulmonar/diagnóstico por imagemRESUMO
Conventional spherical nucleic acid enzymes (SNAzymes), made with gold nanoparticle (AuNPs) cores and DNA shells, are widely applied in bioanalysis owing to their excellent physicochemical properties. Albeit important, the crowded catalytic units (such as G-quadruplex, G4) on the limited AuNPs surface inevitably influence their catalytic activities. Herin, a hybridization chain reaction (HCR) is employed as a means to expand the quantity and spaces of G4 enzymes for their catalytic ability enhancement. Through systematic investigations, we found that when an incomplete G4 sequence was linked at the sticky ends of the hairpins with split modes (3:1 and 2:2), this would significantly decrease the HCR hybridization capability due to increased steric hindrance. In contrast, the HCR hybridization capability was remarkably enhanced after the complete G4 sequence was directly modified at the non-sticky end of the hairpins, ascribed to the steric hindrance avoided. Accordingly, the improved SNAzymes using HCR were applied for the determination of AFB1 in food samples as a proof-of-concept, which exhibited outstanding performance (detection limit, 0.08 ng/mL). Importantly, our strategy provided a new insight for the catalytic activity improvement in SNAzymes using G4 as a signaling molecule.
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Nanopartículas Metálicas , Ácidos Nucleicos , Aflatoxina B1 , Ouro , Hibridização de Ácido NucleicoRESUMO
Coal-derived carbon nanomaterials possess numerous superior features compared to other classic carbon, such as readily accessible surfaces, tunable pore structure, and facile and precise surface functionalization. Therefore, the controllable preparation of coal-derived carbon nanomaterials is anticipated to be of great significance for the performance improvement and commercialization process of carbon-based perovskite solar cells (C-PSCs). In this study, we successfully synthesized highly stable and commercially valuable graphene oxide (GO) and reduced graphene oxide (rGO) utilizing coal. Compared to traditional methods and commercial graphene, the chemical oxidation and pyrolysis process used in this study is mild and simple, offering the advantages of controlled composition and the absence of other impurities. GO or rGO was incorporated into the top of the SnO2 electron transport layer (ETL) of C-PSCs. Under optimized conditions and ultraviolet-ozone (UVO) irradiation, the ultimate power conversion efficiency (PCE) increased from the unmodified 12.4 to 14.04% (based on rGO) and 15.18% (based on GO), representing improvements of 22 and 31%, respectively. The improved photovoltaic performance is mainly owing to enhanced charge transport capabilities, denser interfacial contacts, improved carrier separation properties, increased conductivity, and abundance of hydrophilic functional groups in GO, which can form more stable hydrogen bonds with SnO2. After being stored at room temperature and ambient humidity for 30 days, the modified, unpacked devices retained 87% of the highest power conversion efficiency (PCE). This study introduces a practical and manageable method to enhance the performance of C-PSCs by using functional carbon nanomaterials derived from coal.
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Degradable biomedical elastomers (DBE), characterized by controlled biodegradability, excellent biocompatibility, tailored elasticity, and favorable network design and processability, have become indispensable in tissue repair. This review critically examines the recent advances of biodegradable elastomers for tissue repair, focusing mainly on degradation mechanisms and evaluation, synthesis and crosslinking methods, microstructure design, processing techniques, and tissue repair applications. The review explores the material composition and cross-linking methods of elastomers used in tissue repair, addressing chemistry-related challenges and structural design considerations. In addition, this review focuses on the processing methods of two- and three-dimensional structures of elastomers, and systematically discusses the contribution of processing methods such as solvent casting, electrostatic spinning, and three-/four-dimensional printing of DBE. Furthermore, we describe recent advances in tissue repair using DBE, and include advances achieved in regenerating different tissues, including nerves, tendons, muscle, cardiac, and bone, highlighting their efficacy and versatility. The review concludes by discussing the current challenges in material selection, biodegradation, bioactivation, and manufacturing in tissue repair, and suggests future research directions. This concise yet comprehensive analysis aims to provide valuable insights and technical guidance for advances in DBE for tissue engineering.
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Materiais Biocompatíveis , Elastômeros , Medicina Regenerativa , Engenharia Tecidual , Humanos , Elastômeros/química , Materiais Biocompatíveis/química , AnimaisRESUMO
Surfactants are considered as typical emerging pollutants, their extensive use of in disinfectants has hugely threatened the ecosystem and human health, particularly during the pandemic of coronavirus disease-19 (COVID-19), whereas the rapid discrimination of multiple surfactants in environments is still a great challenge. Herein, we designed a fluorescent sensor array based on luminescent metal-organic frameworks (UiO-66-NH2@Au NCs) for the specific discrimination of six surfactants (AOS, SDS, SDSO, MES, SDBS, and Tween-20). Wherein, UiO-66-NH2@Au NCs were fabricated by integrating UiO-66-NH2 (2-aminoterephthalic acid-anchored-MOFs based on zirconium ions) with gold nanoclusters (Au NCs), which exhibited a dual-emission features, showing good luminescence. Interestingly, due to the interactions of surfactants and UiO-66-NH2@Au NCs, the surfactants can differentially regulate the fluorescence property of UiO-66-NH2@Au NCs, producing diverse fluorescent "fingerprints", which were further identified by pattern recognition methods. The proposed fluorescence sensor array achieved 100% accuracy in identifying various surfactants and multicomponent mixtures, with the detection limit in the range of 0.0032 to 0.0315 mM for six pollutants, which was successfully employed in the discrimination of surfactants in real environmental waters. More importantly, our findings provided a new avenue in rapid detection of surfactants, rendering a promising technique for environmental monitoring against trace multicontaminants.
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OBJECTIVES: Imipenem-relebactam (IMR), a novel ß-lactam/ß-lactamase inhibitor combination, is recommended for infections caused by difficult-to-treat Pseudomonas aeruginosa. This study aimed to investigate the evolution trajectory of IMR resistance under the selection of levofloxacin in P. aeruginosa. METHODS: Antimicrobial susceptibility testing, complete genome sequencing and gene manipulation experiments were performed. Quantitative reverse transcription PCR for specific genes and porin levels were detected. Evolution trajectory was simulated in vitro by induction assay. RESULTS: P. aeruginosa HS347 and HS355 were isolated from abdominal drainage of two neighbouring patients (S and Z) undergoing surgery of colon carcinoma in Shanghai, China, with the latter patient having received levofloxacin. They were closely related ST16 strains, and both carried blaKPC-2 plasmids highly similar to those of P. aeruginosa endemic clones from Zhejiang province, where patient Z had received enteroscopy before this admission. Acquisition of resistance was observed for both IMR and fluoroquinolones in HS355, likely prompted by treatment with levofloxacin. The T274I substitution in MexS (putative oxidoreductase), upregulated efflux pump operon mexEF-oprN and decreased production of porin OprD leading to cross-resistance to fluoroquinolones and IMR, which was also verified by in vitro mutant selection under levofloxacin selection. CONCLUSIONS: The emergence of a rare blaKPC-2-plasmid-bearing ST16 clone implies the horizonal spread and inter-regional dissemination of a high-risk plasmid-clone combination, representing a public health challenge. Levofloxacin exposure can select for mexS inactivating mutation, which in turn leads to IMR resistance phenotype, implicating the role of an unrelated, widely used antimicrobial agent in insidiously triggering the development of cross resistance to a latest ß-lactam/ß-lactamase inhibitor combination.
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Antibacterianos , Compostos Azabicíclicos , Imipenem , Levofloxacino , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , beta-Lactamases , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Levofloxacino/farmacologia , Humanos , Compostos Azabicíclicos/farmacologia , Imipenem/farmacologia , beta-Lactamases/genética , Antibacterianos/farmacologia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , China , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Mutação , Inibidores de beta-Lactamases/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Plasmídeos/genéticaRESUMO
BACKGROUND: Metabolic (dysfunction)-associated fatty liver disease is the most common liver disease related to various metabolic disorders. Colorectal adenomas are related to metabolic dysregulation. Despite the proposed association between non-alcoholic fatty liver disease and colorectal adenomas, the influence of metabolic-associated fatty liver disease on colorectal adenomas has yet to be investigated. Our study investigates the relationship between metabolic-associated fatty liver disease and colorectal adenomas and evaluates the predictive value of fatty liver index for colorectal adenomas. METHODS: A retrospective cross-sectional study was conducted on 650 inpatients at Qinghai Provincial People's Hospital. All participants underwent colonoscopy, abdominal ultrasound or CT, relevant laboratory tests, and physical examinations to ascertain baseline characteristics and overall health status. Multivariate logistic regression analysis examined the relationship between metabolic-associated fatty liver disease and colorectal adenomas. Lastly, the ability to identify, accuracy, and clinical applicability of predicting colorectal adenomas through fatty liver index were assessed using receiver operating characteristic curve area under the curve, calibration curve, and decision curve analysis. RESULT: In both the colorectal adenomas and control groups, the prevalence of metabolic-associated fatty liver disease was 62.1 % and 35.7 %, respectively. Multivariate analysis indicates that metabolic-associated fatty liver disease was independently correlated with an increased risk of colorectal adenomas (OR, 1.565; 95 % CI, 1.057-2.319; P < 0.05). Further analysis revealed that the risk of colorectal adenomas increased with an increasing quantity of metabolic components in metabolic-associated fatty liver disease (Ptrend < 0.001). The area under the curve of the fatty liver index predictive model was 0.838, with a 95 % CI of 0.807-0.869. The calibration curve indicated excellent agreement, and the decision curve analysis revealed a higher net benefit. CONCLUSION: The risk of colorectal adenomas was associated with metabolic-associated fatty liver disease, and the risk of developing colorectal adenomas increased with the presence of more metabolic-associated fatty liver disease metabolic components. Furthermore, fatty liver index served as a predictive indicator for screening colorectal adenomas.
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Adenoma , Neoplasias Colorretais , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores de Risco , Estudos Retrospectivos , Estudos Transversais , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/diagnóstico , Adenoma/etiologiaRESUMO
The Bacteriophage Exclusion (BREX) system is a novel antiphage defense system identified in Bacillus cereus in 2015. The purpose of this study was to investigate the presence of the BREX system defenses against antibiotic-resistant plasmids such as blaKPC and blaNDM invasion in Escherichia coli. The BREX system was present in 5.4% (23/424) of E. coli clinical isolates and 6.5% (84/1283) of E. coli strains with completely sequenced genomes in the GenBank database. All 23 BREX-positive E. coli clinical isolates were susceptible to carbapenems, while all five isolates carrying blaKPC and 11 carrying blaNDM were BREX-negative. For E. coli strains in the GenBank database, 37 of 38 strains carrying blaKPC and 109 of 111 strains carrying blaNDM were BREX negative. The recognition site sequence of methyltransferase PglX in a clinical E. coli 3756 was 5'-CANCATC-3' using PacBio single-molecular real-time sequencing. The transformation efficiency of plasmid psgRNA-ColAori-target with the PglX recognition site was reduced by 100% compared with the plasmid without the recognition site in E. coli DH5α-pHSG398-BREX. The BREX showed lower defense efficacy against plasmid psgRNA-15Aori-target which had the same plasmid backbone but different surrounding sequences of recognition sites with psgRNA-ColAori-target. The conjugation frequency of the KPC-2 plasmid and NDM-5 plasmid in E. coli 3756-ΔBREX was higher than that in E. coli 3756 clinical isolate (1.0 × 10-6 vs 1.3 × 10-7 and 5.5 × 10-7 vs 1.7 × 10-8, respectively). This study demonstrated that the type I BREX system defends against antibiotic-resistant plasmids in E. coli.
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Bacteriófagos , Infecções por Escherichia coli , Humanos , Escherichia coli , Antibacterianos/farmacologia , beta-Lactamases/genética , Plasmídeos/genética , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Paclitaxel, a tubulin-binding agent, is a Food and Drug Administration-approved first-line drug for the treatment of non-small cell lung cancer (NSCLC), for both squamous and non-squamous cell lung carcinoma, with paclitaxel/carboplatin + bevacizumab a common chemotherapy regimen for stage IV non-squamous NSCLC; however, primary or acquired resistance to paclitaxel is gradually increasing, leading to treatment failure. METHODS: Our results show that Ras-related C3 botulinum toxin substrate 3 (RAC3) is overexpressed in cultured paclitaxel-resistant cells and that RAC3 expression levels are negatively correlated with sensitivity of lung adenocarcinoma cells to paclitaxel. Pulsatilla saponin D could inhibit RAC3 expression, and we hypothesize that it may block paclitaxel resistance. Further, we found that treatment with paclitaxel combined with Pulsatilla saponin D, can overcome lung adenocarcinoma cell resistance to paclitaxel alone in cell culture and mouse xenograft models.
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Adenocarcinoma de Pulmão , Toxinas Botulínicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Saponinas , Estados Unidos , Humanos , Animais , Camundongos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma de Pulmão/tratamento farmacológico , Modelos Animais de Doenças , Proteínas rac de Ligação ao GTPRESUMO
Introduction: Carbapenem-Resistant Enterobacteriaceae (CRE) has posed a significant threat to humans.The aim of this study was to investigate the molecular characteristics of blaKPC-producing Escherichia coli in a university-affiliated tertiary hospital. Methods: Polymerase chain reaction (PCR) and BLAST+ software were used to detect the prevalence of blaKPC in E. coli and Klebsiella pneumoniae. Whole-genome sequencing was performed for the blaKPC-harboring clinical E. coli isolates. Antimicrobial resistance genes, MLSTs, KPC-carrying plasmid typing and genetic environment of blaKPC were analyzed. A maximum likelihood core single nucleotide polymorphism (SNP)-based phylogeny tree was constructed to determine the evolutionary relationships within this ST131 collection. Conjugation experiments were performed to determine the mobilization of blaKPC. The minimal inhibitory concentrations of the common antimicrobial agents were determined using the broth microdilution method. Results: The prevalence of blaKPC in 424 clinical E. coli isolates and 1636 E. coli strains from GenBank database were 2.2% (45/2060) whereas the detection rate of blaKPC in K. pneumoniae from the GenBank database was 29.8% (415/1394). The blaKPC-harboring conjugants exhibited resistance to multiple ß-lactams, except for cefepime-zidebactam and ceftazidime-avibactam. All blaKPC-carring E. coli isolates were susceptible to tigecycline and polymyxin B. ST131 was the dominant sequence type of blaKPC-carring E. coli, accounting for 40.0% (18/45). Most of the blaKPC-producing ST131 E. coli (89.5%,17/19) belonged to clade C ST131 lineage. Genetic environment analysis revealed that 57.8% (26/45) of blaKPC gene was linked to Tn4401-associated structure ISKpn6-blaKPC-ISKpn7. IncN was the most common plasmid type in KPC-producing E. coli whereas IncFII was the dominant plasmid type in KPC-producing K. pneumoniae. Conclusion: The detection rate of blaKPC was lower in E. coli compared with K. pneumoniae. The dominant sequence and plasmid types of blaKPC-harboring isolates differed between E. coli and K. pneumoniae. Further studies about the role of the defense system in acquisition of KPC-plasmids in E. coli will be performed to provide new insights into the low prevalence of blaKPC.
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Aflatoxin B1 (AFB1) is considered as a serious carcinogenic mycotoxin that was widely detected in grains and foods, and its sensitive analysis is of key importance to avoid the health threats for consumers. In this study, a dual-signal aptasensor based on cascade of entropy-driven strand displacement reaction (ESDR) and linear rolling circle amplification (LRCA) was fabricated for ultrasensitive determination of AFB1. At the sensing system, the complementary strand would be released after the aptamer combined with AFB1, which will bring about the functional domains exposed, triggering the subsequent ESDR. Meanwhile, the two strands that were outputted by ESDR would incur the downstream LRCA reaction to produce a pair of long strands to assist in the generation of fluorescence and absorbance signals. Under the optimized conditions, the proposed aptasensor could achieve excellent sensitivity (limit of detection, 0.427 pg/mL) with satisfactory accuracy (recoveries, 92.8-107.9 %; RSD, 2.4-5.0 %), mainly ascribed to the cascade amplification. Importantly, owing to the flexibility design of nucleic acid primer, this analytical method can be applied in monitoring various hazardous substances according to the specific requirements. Our strategy provides some novel insights at signal amplification for rapid detection of AFB1 and other targets.
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Aptâmeros de Nucleotídeos , Benzenossulfonatos , Técnicas Biossensoriais , Aflatoxina B1/análise , Técnicas Biossensoriais/métodos , Limite de DetecçãoRESUMO
OBJECTIVE: To explore the risk factors of the peripherally inserted central catheter (PICC)-related venous thrombosis and correspondingly construct a nomogram risk prediction model. METHODS: The clinical data of 401 patients receiving PICC catheterization in our hospital from June 2019 to June 2022 were retrospectively analyzed. The independent influencing factors for venous thrombosis were predicted using logistic regression analysis, and significant indicators were screened to construct a nomogram for predicting PICC-related venous thrombosis. The difference in predictive efficacy between simple clinical data and nomogram was analyzed using a receiver operating characteristic (ROC) curve, and the nomogram was internally validated. RESULTS: Single-factor analysis showed that catheter tip position, plasma D-dimer concentration, venous compression, malignant tumor, diabetes, history of thrombosis, history of chemotherapy, and history of PICC/CVC catheterization were correlated with PICC-related venous thrombosis. Further multi-factor analysis revealed that catheter tip position, plasma D-dimer elevation, venous compression, history of thrombosis and history of PICC/CVC catheterization were the risk factors for PICC-related venous thrombosis. Based on binary logistic regression analysis, a nomogram prediction model for PICC-related venous thrombosis was constructed. The area under the curve (AUC) was 0.876 (95%CI: 0.818-0.925), with a statistically significant difference (P < 0.01). CONCLUSION: The independent risk factors for PICC-related venous thrombosis are screened out, including catheter tip position, plasma D-dimer elevation, venous compression, history of thrombosis and history of PICC/CVC catheterization, and a nomogram prediction model with good effect is constructed to predict the risk of PICC-related venous thrombosis.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Trombose , Trombose Venosa , Humanos , Cateterismo Venoso Central/efeitos adversos , Estudos Retrospectivos , Nomogramas , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Fatores de Risco , Cateteres Venosos Centrais/efeitos adversos , Trombose/complicaçõesRESUMO
This study aims to develop and validate a prognostic nomogram that accurately predicts the short-term survival rate of cirrhotic patients with acute kidney damage (AKI) upon ICU admission. For this purpose, we examined the admission data of 3060 cirrhosis patients with AKI from 2008 to 2019 in the MIMIC-IV database. All included patients were randomly assigned to derivation and validation cohorts in a 7:3 ratio. The derivation cohort used the least absolute shrinkage and selection operator (LASSO) regression model to identify independent predictors of AKI. A prognostic nomogram was constructed via multivariate logistic regression analysis in the derivation cohort and subsequently verified in the validation cohort. Nomogram's discrimination, calibration, and clinical utility were evaluated using the C-index, calibration plot, and decision curve analysis (DCA). A total of 2138 patients were enrolled in the derivation cohort, with a median follow-up period of 15 days, a median survival time of 41 days, and a death rate of 568 patients (26.6%). The cumulative survival rates at 15 and 30 days were 75.8% and 57.5%, respectively. The results of the multivariate analysis indicated that advanced AKI stage, use of vasoactive drugs, advanced age, lower levels of ALB, lower mean sBp, longer INR, and longer PT were all independent risk factors that significantly influenced the all-cause mortality of cirrhosis patients with AKI (all p < 0.01). The C-indices for the derivation and the validation cohorts were 0.821 (95% CI 0.800-0.842) and 0.831 (95% CI 0.810-0.852), respectively. The model's calibration plot demonstrated high consistency between predicted and actual probabilities. Furthermore, the DCA showed that the nomogram was clinically valuable. Therefore, the developed and internally validated prognostic nomogram exhibited favorable discrimination, calibration, and clinical utility in forecasting the 15-day and 30-day survival rates of cirrhosis patients with AKI upon admission to the ICU.
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Injúria Renal Aguda , Nomogramas , Humanos , Prognóstico , Cirrose Hepática/complicações , Unidades de Terapia IntensivaRESUMO
Full activation of the NLRP3 inflammasome needs two sequential signals: a priming signal, followed by a second, assembly signal. Several studies have shown that the two signals trigger post-translational modification (PTM) of NLRP3, affecting activity of the inflammasome, however, the PTMs induced by the second signal are less well characterized. Here, we show that the assembly signal involves acetylation of NLRP3 at lysine 24, which is important for the oligomerization and the actual assembly of NLRP3 without affecting its recruitment to dispersed trans-Golgi network (dTGN). Accordingly, NLRP3 inflammasome activation is impaired in NLRP3-K24R knock-in mice. We identify KAT5 as an acetyltransferase able to acetylate NLRP3. KAT5 deficiency in myeloid cells and pharmacological inhibition of KAT5 enzymatic activity reduce activation of the NLRP3 inflammasome, both in vitro and in vivo. Thus, our study reveals a key mechanism for the oligomerization and full activation of NLRP3 and lays down the proof of principle for therapeutic targeting of the KAT5-NLRP3 axis.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Acetilação , Macrófagos/metabolismo , Processamento de Proteína Pós-TraducionalRESUMO
Traditional hybridization chain reaction (HCR) as a popular isothermal amplification technique shows some inevitable disadvantages in bioanalysis due to its relatively slow kinetics, which could be markedly promoted when the HCR initiator occurs under tension. Herein, a poly DNA tetrahedrons (pTDNs)-mediated HCR was successfully constructed to make its initiator in a stretched state by long-range electrostatic forces owing to the superimposed electrostatic interactions derived from the synthesized pTDNs, and it was hypothesized that it could remarkably enhance HCR performance, which was testified by theoretical simulations and experimental studies. Consequently, pTDNs-mediated HCR was applied to develop a novel immunoassay for rapid and sensitive detection of aflatoxin B1 as a proof-of-concept, and its signal amplification was attributed to the increased G4 DNAzyme that loaded on the second antibody. Our work paves a promising way using simple DNA frameworks alone to heighten HCR kinetics for reaction speed improvement and signal amplification in bioanalysis.
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Aflatoxina B1 , DNA Catalítico , Cinética , Hibridização de Ácido Nucleico , DNA , Poli ARESUMO
Surface-enhanced Raman scattering (SERS) is a widely used rapid and noninvasive method for detecting biological substances in serum samples and is commonly employed in disease screening and diagnosis. Solid-state nanoarray SERS substrates used in serum detection may cause spectral instability due to imperfections in the detection method. For the purpose of identifying optimal detection conditions, various dilution levels of the serum were tested in this study. The study found that a complete and stable serum SERS spectrum can be obtained when the serum is diluted by a factor of 50. The study reports the successful preparation of an Au nanocone array (Au NCA) plasmonic substrate with a uniform, controllable microstructure and high activity, achieved through a combination of PS colloidal sphere template-assisted reactive ion etching (RIE) process and magnetron sputtering deposition technology. Based on this substrate, a standard detection scheme was developed to obtain highly stable and repeatable serum SERS spectra. The study verified the reliability of the optimized serum detection scheme by comparing the SERS spectra of serum samples from healthy individuals and gastric cancer patients, and confirmed the potential benefits of the scheme for disease screening and diagnosis.
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Despite evidence suggesting that biochar can retain nutrients, particularly nitrogen (N), and reduce the risks of transport, research on the co-application of biochar with organic and inorganic fertilizer sources is limited. Three laboratory studies (herein referred to as static incubation, column leaching, and batch sorption) were conducted to evaluate the impacts of two biochar materials (pine and grass biochar generated at temperatures of 800 and 400°C, respectively) on N and carbon (C) dynamics in soils amended with different N sources (ammonium nitrate, Class B, and Class AA biosolids). Nitrogen sources were applied at an equivalent rate of 180 kg N ha-1 while biochar was applied at a 1% (w/w) rate. Biochar effects on soil N and C dynamics were variable and dependent on biochar and N sources. A negligible but significant effect of pine biochar in reducing NH4 leaching was observed; however, both biochar materials were ineffective in reducing NO3 or inorganic N leaching. Reductions in leachate NH4 by pine biochar were attributed to relative greater ability of this material to retain NH4 than grass biochar. Both biochar materials exhibited no ability to sorb NO3 . Similarly, biochar had no effect on soil N2 O emissions. Class B biosolids resulted in greater N leaching and soil N2 O emissions compared to other fertilizers. This response was likely due to inherently high levels of inorganic N and moisture, which possibly favored denitrification. Further research is warranted to better understand the underlying mechanisms controlling soil N and C dynamics and responses to co-application with fertilizer sources.