A perovskite-based electrochemiluminescence aptasensor for tetracycline screening.

Tetracyclines are currently the most commonly used class of antibiotics, and their residue issue significantly impacts public health safety. In this study, a surface modification of perovskite with cetyltrimethylammonium bromide led to the generation of stable electrochemiluminescence (ECL) emitters in aqueous systems and improved the biocompatibility of perovskite. A perovskite quantum dot-based ECL sensing strategy was developed. Utilizing the corresponding aptamer of the antibiotics, strain displacement reactions were triggered, disrupting the ECL quenching system composed of perovskite and Ag nanoclusters (Ag NCs) on the electrode surface, generating a signal to achieve quantitative detection of several common tetracycline antibiotics. The perovskite quantum dot provided a strong and stable initial signal, while the efficient catalytic activity of the silver cluster enhanced the recognition sensitivity. Tetracycline, chlortetracycline, and oxytetracycline were used as examples to demonstrate the differentiation and quantitative detection through this method. In addition, the aptasensor exhibited analytical performance with the linear range (0.1-10 µM OTC) and good recovery rates of 94.7% to 101.6% in real samples. This approach has the potential to become a sensitive and practical approach for assessing antibiotic residues.

Exploring disease axes as an alternative to distinct clusters for characterizing sepsis heterogeneity.

PURPOSE: Various studies have analyzed sepsis subtypes, yet the reproducibility of such results remains unclear. This study aimed to determine the reproducibility of sepsis subtypes across multiple cohorts. METHODS: The study examined 63,547 sepsis patients from six distinct cohorts who had similar sepsis-related characteristics (vital signs, lactate, sequential organ failure assessment score, bilirubin, serum, urine output, and Glasgow coma scale). Identical cluster analysis techniques were used, employing 27 clustering schemes, and normalized mutual information (NMI), a metric ranging from 0 to 1 with higher values indicating better concordance, was employed to quantify the clustering solutions' reproducibility. Principal component analysis (PCA) was utilized to obtain the disease axis, and its uniformity across cohorts was evaluated through patterns of feature loading and correlation. RESULTS: The reproducibility of sepsis clustering subtypes across the various studies was modest (median NMI ranging from 0.08 to 0.54). The top-down transfer learning method (model trained on cohorts with greater severity was transferred to cohorts with lower severity score) had a higher NMI value than the bottom-up approach (median [Q1, Q3]: 0.64 [0.49, 0.78] vs. 0.23 [0.2, 0.31], p < 0.001). The reproducibility was greater when the transfer solution was performed within United States (US) cohorts. The PCA analysis revealed that the correlation pattern between variables was consistent across all cohorts, and the first two disease axes were the "shock axis" and "systemic inflammatory response syndrome (SIRS) axis." CONCLUSIONS: Cluster analysis of sepsis patients across various cohorts showed modest reproducibility. Sepsis heterogeneity is better characterized through continuous disease axes that coexist to varying degrees within the same individual instead of mutually exclusive subtypes.

An extracellular electron transfer enhanced electrochemiluminescence aptasensor for Escherichia coli analysis.

As a crucial indicator in food and water safety testing, the detection of Escherichia coli plays a significant role in maintaining environmental sanitation and promoting public health. Herein, based on the electrochemical activity characteristics of E. coli, we established an enhanced electrochemiluminescence aptasensor for E. coli analysis. This study presents a new method for accurate identification by utilizing a double aptamer recognition system. Specifically, a nano-cadmium sulfide (CdS) modified aptamer was used for primary labeling, while a second aptamer was immobilized on a graphene/chitosan composite electrode for re-capture. The use of two aptamers improves the accuracy of the identification process. Furthermore, the application of an electrode potential facilitates continuous electron transfer between the electrode and electrochemically active microorganisms, resulting in an enhanced electroluminescence signal in relation to the metabolic status. This strategy possesses better sensitivity, accuracy, and stability, demonstrating its potential for E. coli analysis.

Two desired epitopes of cTnI benefit for preparation of standardized monoclonal antibodies.

Acute myocardial infarction (AMI) is one of the most severe cardiovascular diseases in humans, often resulting in unexpected death. Early detection is critical for patient survival. Sandwich ELISA is a common method for the detection of AMI. However, ELISA kits from different manufacturers can give different results, in part because of the lack of standardized epitopes. Therefore, the purpose of this study was to find two standardized epitopes. We predicted two antigen epitopes and respectively immunize mice to manufacture standardized monoclonal antibodies. Eight monoclonal antibodies were prepared. Monoclonal antibodies 7D2 and 2C3 were selected with high affinity, and their characteristics were explored. The results show that monoclonal antibodies 7D2 and 2C3 can both bind to various modified forms and complexes of cardiac troponin I (cTnI), were not cross-reaction with related antigens of normal human serum and can be paired. Therefore, we deem epitopes 30 to 42 and 77 to 89 standardized epitopes.

JNK inhibitor alleviates apoptosis of fetal neural stem cells induced by emulsified isoflurane.

Isoflurane can provide both neuroprotection and neurotoxicity in various culture models and in rodent developing brains. Emulsified Isoflurane (EI) is an emulsion formulation of isoflurane, while its underlying molecular mechanism of developemental nerve toxicity largely remains unclear. We hypothesized that EI induced fetal neural stem cells (FNSCs) apoptosis, endoplasmic reticulum (ER) stress and c-Jun N-terminal kinase (JNK) activation. FNSCs were isolated from the cortex of SD rats during 14 days of gestation. The cell viability, cell apoptotic rates and the expression of apoptosis-related protein Caspase3, inositol requiring enzyme 1 (IRE1), poly (adenosine diphosphate-ribose) polymerase (PARP), Bax, Bcl-2, JNK, p-JNK and XBP1 were determined. Specific inhibition was performed by siRNA-targeting of JNK in FNSCs. EI could increase the p-JNK, JNK and caspase3 protein expression, the JNK pathway was activated by EI, and EI-induced apoptosis was blocked by inhibiting JNK pathway with SP600125 or JNK-small interfering RNA (siRNA), EI enhanced the level of IRE1, PARP, Bax/Bcl-2 and XBP1, which led FNSCs to apoptosis and ER stress. Meanwhile, dilatation of the ER lumens in FNSCs treated by EI for 24 h was significant. Green fluorescent protein (GFP) positive cell ratios were significantly decreased by FNSCs transfecting with JNK gene silencing. JNK was efficiently silenced in siRNA-JNK1 group. The results provided in-vitro evidence which supports that the underlying mechanisms of EI-induced apoptosis are the induction of ER stress and sequent JNK activation. Together, these data suggest that JNK inhibiting might be applied for improving therapeutic outcomes in anesthestics-induced neurotoxicity. HIGHLIGHTS: 1. Prolonged treatment with high-dose EI decreased the survival level of FNSCs by inducing apoptosis and inhibiting proliferation via the JNK signaling pathway. 2. EI induced ER stress and sequent JNK activation. 3. JNK inhibiting might be applied for improving therapeutic outcomes in anesthestics-induced neurotoxicity.

Risk assessment of morbidly obese parturient in cesarean section delivery: A prospective, cohort, single-center study.

BACKGROUND: Up to 40% of women gain excessive weight during pregnancy. Obesity complications and risks in parturient women undergoing cesarean section (CS) with different anesthetic methods remain unknown. This study aimed to assess the safety and risk of obese women undergoing CS delivery with various perioperative anesthetic methods. METHODS: Seven hundred ninety parturient women underwent CS under general anesthesia (GA), intraspinal anesthesia including epidural anesthesia (EA) and combined spinal-epidural anesthesia (CSEA). They were divided into morbid (n = 255), severe (n = 274), and non-obesity (n = 261) groups. This study is registered with ClinicalTrials.gov (number NCT03002636). RESULT: Between 2013 and 2016, 790 pregnant were assessed. Compared with the non-obesity group, there were significantly more fetal distress and higher body mass index (BMI) in the morbid obesity group (P = .0001 and P = .001, respectively). Significantly more patients showed preeclampsia, multifetation, amniotic fluid abnormality, and high bleeding amounts in the morbid obesity group compared with the non-obesity group (P = .0001, P = .048, P = .017, and P = .018, respectively); more patients were administered EA and GA compared with the non-obesity group (P = .0001 and P = .0001, respectively). More post-anesthesia care unit (PACU) patients were found in the severe obesity group no more than the non-obesity group. Significantly increased anesthesia puncture times for 5 > n ≥ 3 and n ≥ 5 were obtained in the morbid obesity group (P = .0001 and P = .0001, respectively), with more patients in the puncture sitting position, compared with the non-obesity group (P = .0001). CONCLUSION: GA, EA, and CSEA are safe and effective in severely or morbidly obese patients. Morbidly obese parturient show increased likelihood for fetal distress, PACU, sitting position puncture, puncture difficulty, and other pregnancy complications. There were more anesthesia puncture times in morbidly obese patients.

Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase-mediated damage of rat fetal neural stem cells.

Increasing studies have demonstrated that sevoflurane can induce neurotoxicity in the developing brains. JNK normally promotes apoptosis. It was hypothesized that sevoflurane affected the proliferation and differentiation of FNSCs and induced cell apoptosis, which caused the learning and memory deficits via JNK pathway. Sevoflurane at a concentration of 1.2% did not induce damage on the FNSCS. However, concentrations of 2.4% and 4.8% decreased the cell viability, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and increased apoptosis, as shown by flow cytometry. The 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay demonstrated that 4.8% sevoflurane reduced the proliferation of FNSCs. Compared with the control group, the 4.8% sevoflurane group showed a decrease in the proportion of undifferentiated FNSCs at 6-h exposure; 4.8% sevoflurane could increase the p-JNK/JNK ratio. JNK inhibition by the specific inhibitor SP600125 enhanced partially the cell viability. Cumulatively, 4.8% sevoflurane induced significant damage on FNSCs; it decreased cell proliferation and proportion of undifferentiated cells as well. JNK pathway might play a key role in the decrease in survival of FNSCs induced by an inhaled anesthetic. The present findings might raise the possibility that JNK inhibition has therapeutic potential in protecting FNSCs from the adverse effects of the inhaled anesthetic.

Suitable depth of epidural puncture in nulliparous pregnant woman.

We study the suitable depth for epidural puncture in primiparas so as to decrease epidural complications and provide anesthesiologists with an appropriate insertion guide. A prospective study of 87 primipara patients receiving labor analgesia who had epidural punctures in the course of vaginal delivery were randomly divided into 3 groups: the L 3,4 group (N = 27), the L 2,3 group (N = 29), and the L 1,2 group (N = 26). Predictive statistical models were used for the formulation of the ideal epidural puncture needle depth. Eighty two patients who had non-traumatic epidural punctures were studied. There were no significant changes in age, weight, height, weight/height ratio, gestational weeks, fetus weight, pregnancy weight, weight difference, and fetus weight (P > 0.05). Compared with L 3,4 intervertebral space, the puncture depth in L 1,2 and L 2,3 was significantly shorter (P < 0.05) and (P < 0.001), respectively; Regression equation: PD (cm) = 0.351 [LHZ] + 0.147 [BMI] + 0.017. The correlation coefficient for LHZ was 0.351 (95 % CI 0.278-0.424; P < 0.001), the correlation coefficient for BMI was 0.147 (95 % CI 0.123-0.171; P < 0.001). This formula is accurate and practical with less complex calculations. However, further validation through a prospective study will be required. It is an accurate way to localize the puncture site in parturients and improve the efficiency of puncture in parturients for analgesia labor.Epidural puncture depth prediction in L 1,2, L 2,3, and L 3,4 can supply with a related reference.