Cascade Signal Amplification Based on Copper Nanoparticle-Reported Rolling Circle Amplification for Ultrasensitive Electrochemical Detection of the Prostate Cancer Biomarker

An ultrasensitive and highly selective electrochemical assay was first attempted by combining the rolling circle amplification (RCA) reaction with poly­(thymine)-templated copper nanoparticles (CuNPs) for cascade signal amplification. As proof of concept, prostate specific antigen (PSA) was selected as a model target. Using a gold nanoparticle (AuNP) as a carrier, we synthesized the primer–AuNP–aptamer bioconjugate for signal amplification by increasing the primer/aptamer ratio. The specific construction of primer–AuNP–aptamer/PSA/anti-PSA sandwich structure triggered the effective RCA reaction, in which thousands of tandem poly­(thymine) repeats were generated and directly served as the specific templates for the subsequent CuNP formation. The signal readout was easily achieved by dissolving the RCA product-templated CuNPs and detecting the released copper ions with differential pulse stripping voltammetry. Because of the designed cascade signal amplification strategy, the newly developed method achieved a linear range of 0.05–500 fg/mL, with a remarkable detection limit of 0.020 ± 0.001 fg/mL PSA. Finally, the feasibility of the developed method for practical application was investigated by analyzing PSA in the real clinical human serum samples. The ultrasensitivity, specificity, convenience, and capability for analyzing the clinical samples demonstrate that this method has great potential for practical disease diagnosis applications

Biosensing <i>Vibrio cholerae</i> with Genetically Engineered <i>Escherichia coli</i>

Cholera is a potentially mortal, infectious disease caused by <i>Vibrio cholerae</i> bacterium. Current treatment methods of cholera still have limitations. Beneficial microbes that could sense and kill the <i>V. cholerae</i> could offer potential alternative to preventing and treating cholera. However, such <i>V. cholerae</i> targeting microbe is still not available. This microbe requires a sensing system to be able to detect the presence of <i>V. cholera</i> bacterium. To this end, we designed and created a synthetic genetic sensing system using nonpathogenic <i>Escherichia coli</i> as the host. To achieve the system, we have moved proteins used by <i>V. cholerae</i> for quorum sensing into <i>E. coli</i>. These sensor proteins have been further layered with a genetic inverter based on CRISPRi technology. Our design process was aided by computer models simulating <i>in vivo</i> behavior of the system. Our sensor shows high sensitivity to presence of <i>V. cholerae</i> supernatant with tight control of expression of output GFP protein

Time evolution of the average distance of infected nodes from the center of the lattice in network A.

<p>The infection rate is <i>λ</i> = 0.24. Initially, 16 nodes in the center of network A are infected. The density of interconnection links is <i>q</i> = 1. The spatial length is <i>R</i> = 1. The network size is <i>N</i> = 10000. The results have been averaged over 100 realizations.</p

Data_Sheet_1_Progressive pulmonary fibrosis in myositis-specific antibody-positive interstitial pneumonia: a retrospective cohort study.docx

ObjectivesIdiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP.MethodsThis descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients’ medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia.ResultsA total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan–Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936–5.392, p = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072–10.017, p = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974–38.157, p = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115–0.899, p = 0.031).ConclusionApproximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP.</p

Epidemic threshold <i>λ</i>_<i>c</i> as a function of the rewiring probability for different spatial constraints <i>R</i> on the interconnection links.

<p>For a given rewiring probability <i>p</i> and a given spatial constraint <i>R</i>, we gradually increase the infection rate <i>λ</i> and find the corresponding infection density in the steady state for each infection rate. We consider <i>λ</i>_<i>c</i> as the first <i>λ</i> value corresponding to a non-zero infection density in the steady state. Each component network has a small-world topology with a rewiring probability <i>p</i>. The density of the interconnection links is <i>q</i> = 1. Initially, 10% of the nodes in network A are randomly chosen to be infected. The network size is <i>N</i> = 10000. The results have been averaged over 100 realizations.</p

Density <i>ρ</i> of infected nodes as a function of the infection rate <i>λ</i> for various rewiring probabilities.

<p><i>ρ</i> is the average of the infection density <i>ρ</i>_<i>A</i> and <i>ρ</i>_<i>B</i>. The density of the interconnection links is <i>q</i> = 1, and the spatial length constraint is <i>R</i> = 1. Initially, 10% of the nodes in network A are randomly chosen to be infected. The network size is <i>N</i> = 10000. The results have been averaged over 100 realizations.</p

Epidemic spreading process in interconnected small-world networks.

<p>(a) illustrates the epidemic spreading pattern in network A. Initially, 16 nodes in the center of network A are infected. The rewiring probabilities are <i>p</i> = 0.1 ((1), (3)) and <i>p</i> = 1 ((2), (4)), and the infection rates are <i>λ</i> = 0.19 ((1), (2)) and <i>λ</i> = 0.24 ((3), (4)). (b) and (c) present the infection density <i>ρ</i>_<i>A</i> in network A as a function of time for two interconnected networks. Initially, 10% of the nodes in network A are randomly chosen to be infected. The infection rates are <i>λ</i> = 0.24 (b) and <i>λ</i> = 0.48 (c). The density of interconnection links is <i>q</i> = 1. The spatial length is <i>R</i> = 1. The network size is <i>N</i> = 10000. The results have been averaged over 100 realizations.</p

Genetic polymorphism of pharmacogenomic VIP variants in the Deng people from the Himalayas in Southeast Tibet

<div><p></p><p>Little is known about polymorphic distribution of pharmacogenes among ethnicities, including the Deng people. In this study, we recruited 100 unrelated, healthy Deng people and genotyped them with respect to 76 different single-nucleotide polymorphisms by the PharmGKB database. Our results first indicated that the polymorphic distribution of pharmacogenes of the Deng people is most similar to CHD, suggesting that Deng people have a closest genetic relationship with CHD. Our data will enrich the database of pharmacogenomics and provide a theoretical basis for safer drug administration and individualized treatment plans, promoting the development of personalized medicine.</p></div

Data_Sheet_1_Can patient gratitude expression boost innovative performance? The role of work meaningfulness and supervisory support.XLSX

Based on emotions as social information (EASI) theory, the current study proposed how and when patient gratitude expression could promote nurses’ innovative performance. Using a time-lagged data of 649 nurses from three class A tertiary hospitals in China, the results showed that patient gratitude expression was positively related to nurses’ innovative performance, and nurses’ work meaningfulness mediated such effect. Furthermore, supervisory support moderated the relationship of work meaningfulness with nurses’ innovative performance, as well as the indirect relationship between patient gratitude expression and innovative performance through work meaningfulness, such that the indirect relationship was stronger when supervisory support is higher. Our research helps to expand our understanding of how patient gratitude expression as an organizational external factor influences nurses’ innovation in healthcare, and meanwhile, provides management insights for hospital managers to focus on patient gratitude expression and enhance nurse innovation.</p

Expression levels of 8 miRNAs in sepsis non-survivors and survivors in a confirmation set.

<p>These 8 miRNAs were significantly differentially expressed between sepsis non-survivors and survivors after qRT-PCR validation in a smaller study sample. Then, these were checked by qRT-PCR in a larger study sample size (Non-survivors = D, n = 73; Survivors = S, n = 93). Only 6 of the 8 miRNAs remained as significantly different between the D group and S groups. Expression levels of these 8 miRNAs were normalized to U6 snRNA U6 snRNA above normal controls and given as fold-changes (2^–ΔΔCt ), △△Ct =  (Ct_miRNA-Ct_U6_snRNA)_patients-(Ct_miRNA-Ct_{U6 snRNA})_controls. Mann-Whitney U-test or student t-test was used for statistical comparisons.</p