FHB resistance conferred by Fhb1 is under inhibitory regulation of two genetic loci in wheat (Triticum aestivum L.).

KEY MESSAGE: Two loci inhibiting Fhb1 resistance to Fusarium head blight were identified through genome-wide association mapping and validated in biparental populations. Fhb1 confers Fusarium head blight (FHB) resistance by limiting fungal spread within spikes in wheat (type II resistance). However, not all lines with Fhb1 display the expected resistance. To identify genetic factors regulating Fhb1 effect, a genome-wide association study for type II resistance was first performed with 72 Fhb1-carrying lines using the Illumina 90 K iSelect SNP chip. Of 84 significant marker-trait associations detected, more than half were repeatedly detected in at least two environments, with the SNPs distributed in one region on chromosome 5B and one on chromosome 6A. This result was validated in a collection of 111 lines with Fhb1 and 301 lines without Fhb1. We found that these two loci caused significant resistance variations solely among lines with Fhb1 by compromising the resistance. In1, the inhibitory gene on chromosome 5B, was in close linkage with Xwgrb3860 in a recombinant inbred line population derived from Nanda2419 × Wangshuibai and a double haploid (DH) population derived from R-43 (Fhb1 near isogenic line) × Biansui7 (with Fhb1 and In1); and In2, the inhibitory gene on chromosome 6A, was mapped to the Xwgrb4113-Xwgrb4034 interval using a DH population derived from R-43 × PH8901 (with Fhb1 and In2). In1 and In2 are present in all wheat-growing areas worldwide. Their frequencies in China's modern cultivars are high but have significantly decreased in comparison with landraces. These findings are of great significance for FHB resistance breeding using Fhb1.

LiFT (a Lithium Fiber-Based Test): An At-Home Companion Diagnostics for a Safer Lithium Therapy in Bipolar Disorder.

This work presents LiFT (a lithium fiber-based test), a low-cost electrochemical sensor that can measure lithium in human saliva and urine with FDA-required accuracy. Lithium is used for the treatment of bipolar disorder, and has a narrow therapeutic window. Close monitoring of lithium concentration in biofluids and adjustment of drug dosage can minimize the devastating side effects. LiFT is an inexpensive, yet accurate and simple-to-operate lithium sensor for frequent at-home testing for early identification of lithium toxicity. The low cost and high accuracy of LiFT are enabled through an innovative design and the use of ubiquitous materials such as yarn and carbon black for fabrication. LiFT measures Li+ through potentiometric recognition using a lithium selective sensing membrane that is deposited on the ink-coated yarn. A detection limit of 0.97 µM is obtained with a sensitivity of 59.07±1.25 mV/decade for the Li+ sensor in deionized water. Moreover, the sodium correction extended LiFT's linear range in urine and saliva to 0.5 mM. The LiFT platform sends the test results to the patient's smartphone, which subsequently can be shared with the patient's healthcare provider to expedite diagnosis and prevention of acute lithium toxicity.

Validation of a new kit for preeclampsia screening: A comprehensive analysis.

Objectives: Preeclampsia is a common pregnancy complication that significantly contributes to maternal mortality, perinatal mortality, and preterm delivery. The sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio has demonstrated robust diagnostic value for preeclampsia. This study assessed the analytical performance and diagnostic accuracy of a novel quantitative determination kit for sFlt-1 and PlGF for the diagnosis of preeclampsia. Methods: The detection performance of the test kit was validated using the Center for Medical Device Evaluation (CMDE) and Clinical and Laboratory Standards Institute (CLSI) documents. The test results were compared to those of the Elecsys immunoassay (Roche Diagnostics). Independent discovery and validation sets were used to analyze the diagnostic efficacy of the preeclampsia kit. The area under the curve (AUC) for preeclampsia at different gestational ages was calculated. Results: Correlation analysis between the test and Roche kits revealed a strong concordance (sFlt-1: r = 0.9966, P < 0.0001; PlGF: r = 0.9935, P < 0.0001). The AUCs for sFlt-1, PlGF, and the sFlt-1/PlGF ratio in diagnosing preeclampsia were 0.749, 0.795, and 0.834, respectively, in the discovery set and 0.729, 0.811, and 0.831, respectively, in the validation set. The corresponding results from the Roche kit were 0.741, 0.795, and 0.829, respectively, and 0.761, 0.864, and 0.844, respectively. Conclusions: Quantitative sFlt-1 and PlGF kits exhibited high levels of consistency with the Roche kits in terms of quantitative outcomes and diagnostic performance for preeclampsia.

Micronanoparticled risedronate exhibits potent vaccine adjuvant effects.

Micro/Nano-scale particles are widely used as vaccine adjuvants to enhance immune response and improve antigen stability. While aluminum salt is one of the most common adjuvants approved for human use, its immunostimulatory capacity is suboptimal. In this study, we modified risedronate, an immunostimulant and anti-osteoporotic drug, to create zinc salt particle-based risedronate (Zn-RS), also termed particulate risedronate. Compared to soluble risedronate, micronanoparticled Zn-RS adjuvant demonstrated increased recruitment of innate cells, enhanced antigen uptake locally, and a similar antigen depot effect as aluminum salt. Furthermore, Zn-RS adjuvant directly and quickly stimulated immune cells, accelerated the formulation of germinal centers in lymph nodes, and facilitated the rapid production of antibodies. Importantly, Zn-RS adjuvant exhibited superior performance in both young and aged mice, effectively protecting against respiratory diseases such as SARS-CoV-2 challenge. Consequently, particulate risedronate showed great potential as an immune-enhancing vaccine adjuvant, particularly beneficial for vaccines targeting the susceptible elderly.

Toward Personalized Treatment of Depression: An Affordable Citalopram Test based on a Solid-Contact Potentiometric Electrode for at-Home Monitoring of the Antidepressant Dosage.

Citalopram (CTLP) is one of the most common antidepressants prescribed worldwide. It has a narrow therapeutic window and can cause severe toxicity and mortality if the dosage exceeds the safe level. Reports indicated that at-home monitoring of citalopram dosage considerably benefits the patients, yet there are no devices capable of such measurement of citalopram in biofluids. This work presents an affordable citalopram test for at-home and point-of-care monitoring of citalopram levels in urine, ensuring a safe and effective drug compliance. Our platform consists of a citalopram-selective yarn-based electrode (CTLP-SYE) that uses polymeric sensing membranes to provide valuable information about drug concentration in urine. CTLP-SYE is noninvasive and has a response time of fewer than 10 s. The fabricated electrode showed near-Nernstian behavior with a 52.3 mV/decade slope in citalopram hydrobromide solutions ranging from 0.5 µM to 1.0 mM, with a detection limit of 0.2 µM. Results also indicated that neither interfering ions nor pH affects electrode performance. We showed that CTLP-SYE could accurately and reproducibly measure citalopram in human urine (RSD 2.0 to 3.2%, error <12%) at clinically relevant concentrations. This work paves the way for the personalized treatment of depression and accessible companion diagnostics to improve treatment efficacy and safety.