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Thioamycolamide A ( 1 ) is a biosynthetically unique cytotoxic cyclic microbial lipopeptide that bears a d -configured thiazoline, a thioether bridge, a fatty acid side chain, and a reduced C-terminus. It has gained attention for its unique structure, and very recently we reported the total synthesis of 1 via a biomimetic route. The NMR spectra of synthetic 1 agreed with those of natural 1 . However, structural identity between peptidic natural and synthetic compounds is often difficult to confirm by comparison of NMR spectra because their NMR spectra vary depending on the conditions in the NMR tube, which often result in the structural misassignment of peptidic compounds. Especially, our total synthesis based on the putative biomimetic route potentially gives 1 as a diastereomixture at the final step. The problem is that the diastereomers of peptidic mid-sized molecules often exhibit similar properties (such as NMR spectra and bioactivities), and their separation procedures are often laborious. Herein we report the structural confirmation of synthetic 1 by the LC–MS-based chromatographic comparison with the use of our highly sensitive labeling reagent l -FDVDA; the highly sensitive-advanced Marfey’s method (HS-advanced Marfey’s method). This work demonstrated the utility of our highly sensitive labeling reagent for the structural determination of not only scarce natural products but also readily isomerizable synthetic compounds.

Highly sensitive Lens culinaris agglutinin-reactive fraction of α-fetoprotein (hs-AFP-L3) is a specific marker for hepatocellular carcinoma (HCC) and has been reliable in cases with a low serum α-fetoprotein (AFP) level. However, the biomarkers that contribute to hepatocarcinogenesis during the long-term observation are not yet clear. The present study reported the clinical utility of hs-AFP-L3 in the long-term observation of patients with chronic liver disease. The subjects were 106 patients with chronic liver disease without HCC or a history of HCC treatment and who had been followed for >12 months. hs-AFP-L3 was measured using cryopreserved serum. The factors contributing to hepatocarcinogenesis were examined using univariate and multivariate analyses. The median observation period was 88 months (15-132 months). The cumulative incidence of HCC was 10.5% at 5 years and 19.6% at 10 years. The univariate analysis revealed that age ≥55 years old, platelet count ≤13.1x104/µl, hyaluronic acid ≥80.8 ng/ml, alanine transaminase ≥47 U/l, AFP ≥6.3 ng/ml, hs-AFP-L3 ≥3.5% and des-γ-carboxy prothrombin (DCP) ≥25 mAU/ml were significant factors. In the multivariate analysis, platelet count ≤13.1x104/µl [hazard ratio (HR), 4.966; 95% confidence interval (CI), 1.597-15.437; P=0.006] and hs-AFP-L3 ≥3.5% (HR, 5.450; 95% CI, 1.522-19.512; P=0.009) were extracted as significant factors contributing to hepatocarcinogenesis. In addition, for cases with AFP <20 ng/ml, a multivariate analysis revealed that hs-AFP-L3 ≥4.9% (HR, 11.608; 95% CI, 2.422-55.629; P=0.002) and DCP ≥25 mAU/ml (HR, 3.936; 95% CI, 1.088-14.231; P=0.037) were significant factors contributing to hepatocarcinogenesis. hs-AFP-L3 is a useful marker for predicting hepatocarcinogenesis in the long-term observation of patients with chronic liver disease.

This prospective cohort study aimed to evaluate the potential association of ideal cardiovascular health metrics with the plasma levels of highly sensitive C-reactive protein (hs-CRP) among people in North China. A total of 80,968 participants were included in this study at baseline. Data relating to seven health metrics and plasma hs-CRP levels were collected at baseline and the end of follow-up. The change in health metrics of each individual was compared and recorded. The potential association of gain or loss of each health metric, as well as the change in the total number of health metrics that each individual had during follow-up, with the risk of increased hs-CRP level, were explored by multiple Cox proportional hazards models. A total of 72,321 participants (94.51%) completed the follow-up, and the average follow-up time was 4.1 years. Ideal body mass index (BMI), physical activity, smoking status and total cholesterol all had significant impacts on hs-CRP levels, with ideal BMI having the largest impact. Losing ideal BMI during follow-up raised the probability of hs-CRP increase during the follow-up time by 1.72 (95% CI, 1.59-1.86) times for men and 2.05 (95% CI, 1.76-2.39) times for women. The effects of ideal salt intake and blood pressure on hs-CRP levels were uncertain. Changes in the total number of ideal metrics for each individual had a significant cumulative effect on hs-CRP. The hazard ratio of loss of four to six health metrics during follow-up on the risk of hs-CRP increase was 1.69 (95% CI, 1.38-2.06) for men and 1.52 (95% CI, 1.13-2.04) for women. Loss or gain of ideal cardiovascular health metrics is associated with significant fluctuations in plasma hs-CRP levels. The cardiovascular benefits brought by the ideal health metrics are mediated at least in part by reducing systemic inflammation in the body.

It is of great significance for dynamic monitoring of foods in storage or during the transportation process through on-line detecting trimethylamine (TMA). Here, TMA were sensitively detected by Au-modified hierarchical porous single-crystalline ZnO nanosheets (HPSCZNs)-based sensors. The HPSCZNs were synthesized through a one-pot wet-chemical method followed by an annealing treatment. Polyethyleneimine (PEI) was used to modify the surface of the HPSCZNs, and then the PEI-modified samples were mixed with Au nanoparticles (NPs) sol solution. Electrostatic interactions drive Au nanoparticles loading onto the surface of the HPSCZNs. The Au-modified HPSCZNs were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectrum (EDS), respectively. The results show that Au-modified HPSCZNs-based sensors exhibit a high response to TMA. The linear range is from 10 to 300 ppb; while the detection limit is 10 ppb, which is the lowest value to our knowledge.

Children differ in their environmental sensitivity (ES), which can be measured observationally or by self-report questionnaire. A parent-report scale represents an important tool for investigating ES in younger children but has to be psychometrically robust and valid. In the current multistudy, we validated the parent-report version of the Highly Sensitive Child (HSC-PR) scale in Italian children, evaluating its factorial structure (Study 1, N = 1,857, 6.2 years, age range: 2.6–14 years) through a multigroup Confirmatory Factory Analysis in preschoolers ( n = 1,066, 4.2 years) and school-age children ( n = 791, 8.8 years). We then investigated the HSC-PR relationship with established temperament traits (Study 2, N = 327, 4.3 years), before exploring whether the scale moderates the effects of parenting stress on children’s emotion regulation (Study 3, N = 112, 6.5 years). We found support for a bi-factor structure in both groups, though in preschoolers minor adaptations were suggested for one item. Importantly, the HSC-PR did not fully overlap with common temperament traits and moderated the effects of parenting stress on children emotion regulation. To conclude, the HSC-PR performs well and appears to capture ES in children.

Graphene has become a bridge across optoelectronics, mechanics, and bio-chemical sensing due to its unique photoelectric characteristics. Moreover, benefiting from its two-dimensional nature, this atomically thick film with full flexibility has been widely incorporated with optical waveguides such as fibers, realizing novel photonic devices including polarizers, lasers, and sensors. Among the graphene-based optical devices, sensor is one of the most important branch, especially for gas sensing, as rapid progress has been made in both sensing structures and devices in recent years. This article presents a comprehensive and systematic overview of graphene-based microfiber gas sensors regarding many aspects including sensing principles, properties, fabrication, interrogating and implementations.

Glial fibrillary acidic protein (GFAP), microtubule-associated protein tau, and amyloid β peptide (Aβ42) have been proposed as diagnostic and prognostic biomarkers in traumatic brain injury (TBI). Single molecule array (Simoa) is a novel technology that employs highly sensitive immunoassays for accurate measurements of candidate biomarkers found at low concentration in biological fluids. Our objective was to trace the trajectory of tau, GFAP, and Aβ42 levels in plasma from the acute through subacute stages after TBI, compared with controls. Samples from 34 TBI subjects enrolled in the Citicoline Brain Injury Treatment Trial (COBRIT) were studied. Injury severity was assessed by Glasgow Coma Scale (GCS) and admission CT. Glasgow Outcome Scale Extended (GOSE) was assessed 6 months after injury. Plasma was collected within 24 h (Day 0), and 30 and 90 days after the TBI. Plasma collected from 69 healthy volunteers was used for comparison. At every time point, increases were noted in plasma GFAP (p < 0.0001 for all comparisons), tau (p < 0.0001, p < 0.0001, and p = 0.0044, at Days 0, 30, and 90, respectively), and Aβ42 (p < 0.001, p < 0.0001, and p = 0.0203, respectively) in TBI cases compared with controls. The levels were maximal at Day 0 for GFAP and tau and at Day 30 for Aβ42. Area under curve (AUC) analyses for Day 0 GFAP and tau were excellent for discrimination of complicated mild TBI (cmTBI) from controls (0.936 and 0.901, correspondingly). Discriminant component analysis (DCA) for all three biomarkers at Days 0 and 30 differentiated controls from cmTBI (91.1% and 89.7% correctly classified, at each time point). Duration of post-traumatic amnesia (PTA) correlated weakly with tau levels at 30 days (Spearman's r = 0.40; 95% CI 0.0003–0.60, p = 0.044). The Marshall CT Grade on admission correlated weakly with Day 30 tau levels (Spearman's r = 0.41; 95% CI 0.04–0.68, p = 0.027). Day 30 Aβ42 correlated with GOSE (standardized β −0.486, p = 0.042). GFAP, tau and Aβ42 were increased up to 90 days after TBI compared with controls. Total tau levels correlated with clinical and radiological variables of TBI severity. Plasma Aβ42 correlated with clinical outcome. Combination of all three biomarkers at Days 0 and 30 can be used to differentiate controls from cmTBI populations, and may be useful as biomarkers of TBI in both acute and subacute phases.

We investigated changes in highly sensitive lens culinaris agglutinin A‐reactive fraction of alpha‐fetoprotein (hsAFP‐L3) measured using a novel method and its predictive ability for prognosis in patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy, comparing to other HCC tumor markers, that is, AFP, des‐gamma‐carboxy prothrombin (DCP), and AFP‐L3 measured with conventional method (cAFP‐L3). AFP, DCP, and AFP‐L3 including both cAFP‐L3 and hsAFP‐L3 were measured before and after curative hepatectomy in 187 patients. The percentage of patients with elevated tumor marker levels pre‐ and postoperatively was compared, and recurrence‐free and overall survival rates were analyzed based on changes in tumor markers. The percentages of patients with elevated AFP, DCP, and cAFP‐L3 decreased postoperatively. In contrast, the percentage of patients with elevated hsAFP‐L3 did not decrease postoperatively. Both recurrence‐free and overall survival rates were significantly lower in patients whose tumor marker levels remained elevated postoperatively than patients without tumor marker elevation postoperatively. Recurrence‐free and overall survival rates of patients in whom hsAFP‐L3 became elevated postoperatively despite normal preoperative hsAFP‐L3 levels were significantly lower than those of patients with normal hsAFP‐L3 postoperatively, and were similar to those of patients with persistent elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many patients postoperatively, but not for hsAFP‐L3. The elevation of hsAFP‐L3 identifies patients with poor prognosis despite the normalization of AFP and DCP. AFP‐L3, tumor biomarker that is specific for hepatocellular carcinoma (HCC) usually decreases after curative hepatectomy as well as AFP and des‐gamma‐carboxy prothrombin. However, it did not decrease even after curative hepatectomy when AFP‐L3 was measured with highly sensitive method, and this will discriminate the outcome of patients with HCC after hepatectomy.

This study found a strong association between elevated levels of highly sensitive C-reactive protein (hs-CRP) and vital lipid markers in dyslipidemic pre-, peri-,and postmenopausal women, indicating the need to screen them early for atherosclerotic cardiovascular risk. These subjects were advised to make dietary and lifestyle changes to overcome dyslipidemia and prevent the development and progression of atherosclerotic cardiovascular disease (ASCVD) during menopause. No such studies have examined the relationship between hs-CRP and lipid markers, especially in dyslipidemic women. Surprisingly, significant associations were also observed between hs-CRP and triglycerides (TG), as well as between hs-CRP and LDL-cholesterol (LDL-C) in premenopausal women with dyslipidemia. These correlations suggest that hs-CRP and the studied lipid markers are better indicators of the possible onset of ASCVD in women at later ages.

Laboratory diagnosis plays one of the key roles in the diagnosis of many diseases, including cardiovascular diseases (CVD). The methods underlying the in vitro study of many CVD biomarkers, including cardiac troponins (cTnI and cTnT), are imperfect and are continually being improved to enhance their analytical performance, with sensitivity and specificity being the most important. Recently developed improved cTnI and cTnT detection methods, referred to as highly sensitive methods (hs-cTnI, hs-cTnT), have changed many of our ideas about the biology of cardiac troponins and opened up a number of additional diagnostic capabilities for practical healthcare. This article systematizes some relevant data on the biology of cardiac troponins as well as on methods for determining cTnI and cTnT with an analysis of the diagnostic value of their analytical characteristics (limit of blank, limit of detection, 99th percentile, coefficient of variation, and others). Data on extracardiac expression of cTnI and cTnT, mechanisms of formation and potential clinical significance of gender, age, and circadian characteristics of hs-cTnI and hs-cTnT content in serum are discussed. Considerable attention is paid to the discussion of new diagnostic capabilities of hs-cTnI, hs-cTnT, including consideration of promising possibilities for their study in biological fluids that can be obtained by non-invasive methods. Also, some possibilities of using hs-cTnI and hs-cTnT as prognostic laboratory biomarkers in healthy people (for example, to assess the risk of developing CVD) and in patients suffering from a number of pathological conditions that cause damage to cardiomyocytes are examined, and the potential mechanisms underlying the increase in hs-cTnI and hs-cTnT are discussed.