In this article, we describe a disposable nucleic acid biosensor (DNAB) for low-cost and sensitive detection of nucleic acid samples in 15 min. Combining the unique optical properties of gold nanoparticles (Au-NP) and the high efficiency of chromatographic separation, sandwich-type DNA hybridization reactions were realized on the lateral flow strips, which avoid multiple incubation, separation, and washing steps in the conventional nucleic acid biosensors. The captured Au-NP probes on the test zone and control zone of the biosensor produced the characteristic red bands, enabling visual detection of nucleic acid samples without instrumentation. The quantitative detection was performed by reading the intensities of the produced red bands with a portable strip reader. The parameters (e.g., the concentration of reporter probe, the size of Au-NP, the amount of Au-NP-DNA probe, lateral flow membranes, and the concentration of running buffer) that govern the sensitivity and reproducibility of the sensor were optimized. The response of the optimized device is highly linear over the range of 1-100 nM target DNA, and the limit of detection is estimated to be 0.5 nM in association with a 15 min assay time. The sensitivity of the biosensor was further enhanced by using horseradish peroxidase (HRP)-Au-NP dual labels which ensure a quite low detection limit of 50 pM. The DNAB has been applied for the detection of human genomic DNA directly with a detection limit of 2.5 microg/mL (1.25 fM) by adopting well-designed DNA probes. The new nucleic acid biosensor thus provides a rapid, sensitive, low cost, and quantitative tool for the detection of nucleic acid samples. It shows great promise for in-field and point-of-care diagnosis of genetic diseases and detection of infectious agents or warning against biowarfare agents.

Abstract:The insect nicotinic acetylcholine receptor (nAChR) is a major target for insecticide action. The rapidly expanding use of neonicotinoid insecticides of varied structures makes it increasingly important to define similarities and differences in their action, particularly for the first-generation chloropyridinyl compounds versus the second-generation chlorothiazolyl derivatives. We have shown with Musca domestica that a convenient and relevant determination of the neonicotinoid insecticide target is a binding site assay with. This study uses membranes from the aphids Myzus persicae and Aphis craccivora and from heads of the flies Drosophila melanogaster and Musca domestica to characterize the [ 3 H]IMI binding sites relative to their number and possible species variation in structure-activity relationships. With emphasis on commercial neonicotinoids, six potent chloropyridinyl compounds are compared with the corresponding six chlorothiazolyl analogues (syntheses are given for chemicals prepared differently than previously described). The preference for chloropyridinyl versus chlorothiazolyl is not dependent on the insect species examined but instead on other structural features of the molecule. The chlorothiazolyl substituent generally confers higher potency in the clothianidin and desmethylthiamethoxam series and the chloropyridinyl moiety in the imidacloprid, thiacloprid, acetamiprid, and nitenpyram series. Two chlorothiazolyl compounds compete directly with the chloropyridinyl [ 3 H]IMI for the same binding sites in Myzus and Drosophila membranes. This study shows conserved neonicotinoid specificity of the [ 3 H]IMI binding site in each of the four insect species examined.

Background and aims We aim to assess the safety and immunogenicity of inactivated whole-virion SARS-CoV-2 vaccines in patients with chronic liver diseases (CLD) in this study. Methods This was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Results A total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (36 [8.2%]) was the most frequently reported adverse event. Three participants had Grade 3 aminopherase elevation (defined as alanine aminopherase>5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only one of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in non-cirrhotic CLD group, 78.9% in compensated cirrhotic group, 76.7% in decompensated cirrhotic group (P=0.894 among CLD subgroups) and 90.3% in healthy controls (P=0.008 versus CLD group). Conclusion Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunological response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in non-cirrhotic CLD, compensated cirrhosis and decompensated cirrhosis.

Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m 2 (IQR 23.8–28.1 kg/m 2 ). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

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