A highly sensitive bio-barcode immunoassay for multi-residue detection of organophosphate pesticides based on fluorescence anti-quenching

Balancing the risks and benefits of organophosphate pesticides (OPs) on human and environmental health relies partly on their accurate measurement. A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs (triazophos, parathion, and chlorpyrifos) in apples, turnips, cabbages, and rice. Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs. DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification. The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore. The resulting fluorescence signal enables multiplexed quantification of triazophos, parathion, and chlorpyrifos residues over the concentration range of 0.01–25, 0.01–50, and 0.1–50 ng/mL with limits of detection of 0.014, 0.011, and 0.126 ng/mL, respectively. The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%–17.6%, which correlate well with results obtained by LC-MS/MS. The proposed bio-barcode immunoassay is stable, reproducible and reliable, and is able to detect low residual levels of multi-residue OPs in agricultural products.This work was supported by the Central Public Interest Scientific Institution Basal Research Fund for the Chinese Academy of Agricultural Sciences (Grant No.: Y2021PT05), National Institute of Environmental Health Science Superfund Research Program (Grant No.: P42 ES004699), National Academy of Sciences (Subaward No.: 2000009144), and Ningbo Innovation Project for Agro-Products Quality and Safety (Grant No.: 2019CXGC007).Peer reviewe

Network regression analysis in transcriptome-wide association studies.

BACKGROUND: Transcriptome-wide association studies (TWASs) have shown great promise in interpreting the findings from genome-wide association studies (GWASs) and exploring the disease mechanisms, by integrating GWAS and eQTL mapping studies. Almost all TWAS methods only focus on one gene at a time, with exception of only two published multiple-gene methods nevertheless failing to account for the inter-dependence as well as the network structure among multiple genes, which may lead to power loss in TWAS analysis as complex disease often owe to multiple genes that interact with each other as a biological network. We therefore developed a Network Regression method in a two-stage TWAS framework (NeRiT) to detect whether a given network is associated with the traits of interest. NeRiT adopts the flexible Bayesian Dirichlet process regression to obtain the gene expression prediction weights in the first stage, uses pointwise mutual information to represent the general between-node correlation in the second stage and can effectively take the network structure among different gene nodes into account. RESULTS: Comprehensive and realistic simulations indicated NeRiT had calibrated type I error control for testing both the node effect and edge effect, and yields higher power than the existed methods, especially in testing the edge effect. The results were consistent regardless of the GWAS sample size, the gene expression prediction model in the first step of TWAS, the network structure as well as the correlation pattern among different gene nodes. Real data applications through analyzing systolic blood pressure and diastolic blood pressure from UK Biobank showed that NeRiT can simultaneously identify the trait-related nodes as well as the trait-related edges. CONCLUSIONS: NeRiT is a powerful and efficient network regression method in TWAS

A Randomized Clinical Trial of a Functional Electrical Stimulation Mimic to Gait Promotes Motor Recovery and Brain Remodeling in Acute Stroke

Functional electrical stimulation can improve motor function after stroke. The mechanism may involve activity-dependent plasticity and brain remodeling. The aim of our study was to investigate the effectiveness of a patterned electrical stimulation FES mimic to gait in motor recovery among stroke survivors and to investigate possible mechanisms through brain fMRI. Forty-eight subjects were recruited and randomly assigned to a four-channel FES group (n=18), a placebo group (n=15), or a dual-channel FES group (n=15). Stimulation lasted for 30 minutes in each session for 3 weeks. All of the subjects were assessed at baseline and after weeks 1, 2, and 3. The assessments included the Fugl-Meyer Assessment, the Postural Assessment Scale for Stroke Patients, Brunel’s Balance Assessment, the Berg Balance Scale, and the modified Barthel Index. Brain fMRI were acquired before and after the intervention. All of the motor assessment scores significantly increased week by week in all the three groups. The four-channel group showed significantly better improvement than the dual-channel group and placebo groups. fMRI showed that fractional anisotropy was significantly increased in both the four-channel and dual-channel groups compared with the placebo group and fiber bundles had increased significantly on the ipsilateral side, but not on the contralateral side in the group given four-channel stimulation. In conclusion, when four-channel FES induces cycling movement of the lower extremities based on a gait pattern, it may be more effective in promoting motor recovery and induce more plastic changes and brain remodeling than two-channel stimulation. This trial is registered with clinical trial registration unique identifier ChiCTR-TRC-11001615

The Effectiveness of Functional Electrical Stimulation Based on a Normal Gait Pattern on Subjects with Early Stroke: A Randomized Controlled Trial

Objective. To investigate the effectiveness of four-channel FES based on a normal gait pattern on improving functional ability in subjects early after ischemic stroke. Methods. Forty-five subjects were randomly assigned into a four-channel FES group (n=16), a placebo group (n=15), or a dual-channel group (n=14). Stimulation lasted for 30 min in each session with 1 session/day, 5 days a week for 3 weeks. All subjects were assessed at baseline, at 3 weeks of treatment, and at 3 months after the treatment had finished. The assessments included Fugl-Meyer Assessment (FMA), the Postural Assessment Scale for Stroke Patients (PASS), Berg Balance Scale (BBS), Functional Ambulation Category (FAC), and the Modified Barthel Index (MBI). Results. All 3 groups demonstrated significant improvements in all outcome measurements from pre- to posttreatment and further gains at followup. The score of FMA and MBI improved significantly in the four-channel group at the end of the 3 weeks of training. And the scores of PASS, BBS, MBI, and FAC in the four-channel group were significantly higher than those of the placebo group. Conclusions. This study indicated that four-channel FES can improve motor function, balance, walking ability, and performance of activities of daily living in subjects with early ischemic stroke

Anomalous efficiency elevation of quantum-dot light-emitting diodes induced by operational degradation.

Acknowledgements: We thank the technical support of Nano-X from Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (SINANO). We thank Dr R. Huang (SINANO) and Ms Z. Li (SINANO) for the ToF-SIMS and XPS characterizations. We acknowledge financial support from the National Key R&D Program of China (2021YFB3602703 and 2022YFB3606503 (Y.J.); 2021YFA1202802 (Q.C.)), National Natural Science Foundation of China (21975220 (Y.J.); 22022205 and 22372193 (Q.C.)), Key Research and Development Program of Zhejiang Province (2020C01001 (Y.J.)), China Postdoctoral Science Foundation (2021M702800 (Y.D.)) and the CAS Project for Young Scientists in Basic Research (YSBR-054 (Q.C.)).Funder: National Key R&D Program of China (2021YFB3602703, 2022YFB3606503) Key Research and Development Program of Zhejiang Province (2020C01001)Funder: National Key R&D Program of China (2021YFA1202802) CAS Project for Young Scientists in Basic Research (YSBR-054)Quantum-dot light-emitting diodes promise a new generation of high-performance and solution-processed electroluminescent light sources. Understanding the operational degradation mechanisms of quantum-dot light-emitting diodes is crucial for their practical applications. Here, we show that quantum-dot light-emitting diodes may exhibit an anomalous degradation pattern characterized by a continuous increase in electroluminescent efficiency upon electrical stressing, which deviates from the typical decrease in electroluminescent efficiency observed in other light-emitting diodes. Various in-situ/operando characterizations were performed to investigate the evolutions of charge dynamics during the efficiency elevation, and the alterations in electric potential landscapes in the active devices. Furthermore, we carried out selective peel-off-and-rebuild experiments and depth-profiling analyses to pinpoint the critical degradation site and reveal the underlying microscopic mechanism. The results indicate that the operation-induced efficiency increase results from the degradation of electron-injection capability at the electron-transport layer/cathode interface, which in turn leads to gradually improved charge balance. Our work provides new insights into the degradation of red quantum-dot light-emitting diodes and has far-reaching implications for the design of charge-injection interfaces in solution-processed light-emitting diodes

CCR2 Signal Facilitates Thymic Egress by Priming Thymocyte Responses to Sphingosine-1-Phosphate

The signal mediated by sphingosine-1-phosphate receptor 1 (S1P1) is essential but seemingly insufficient for thymic export of newly generated T cells. Here, we reported the identification of CCR2 as an additional regulator of this process. CCR2 showed a markedly increased expression in the most mature subset of single-positive (SP) thymocytes. Its deficiency led to a reduction of recent thymic emigrants in the periphery and a simultaneous accumulation of mature SP cells in the thymus. The CCR2 signaling promoted thymic emigration primarily through modulating the chemotactic responses to S1P1 engagement. On the one hand, the chemokinesis induced by CCR2 activation endowed thymocytes with enhanced capacity to respond to S1P-induced migration. On the other hand, CCR2 signaling through Stat3 augmented forkhead box O1 activity, leading to increased expression of S1P1. Taken together, the present study highlights a unique and novel function of CCR2 signaling in the regulation of thymic egress

Video_5_CCR2 Signal Facilitates Thymic Egress by Priming Thymocyte Responses to Sphingosine-1-Phosphate.MOV

<p>The signal mediated by sphingosine-1-phosphate receptor 1 (S1P1) is essential but seemingly insufficient for thymic export of newly generated T cells. Here, we reported the identification of CCR2 as an additional regulator of this process. CCR2 showed a markedly increased expression in the most mature subset of single-positive (SP) thymocytes. Its deficiency led to a reduction of recent thymic emigrants in the periphery and a simultaneous accumulation of mature SP cells in the thymus. The CCR2 signaling promoted thymic emigration primarily through modulating the chemotactic responses to S1P1 engagement. On the one hand, the chemokinesis induced by CCR2 activation endowed thymocytes with enhanced capacity to respond to S1P-induced migration. On the other hand, CCR2 signaling through Stat3 augmented forkhead box O1 activity, leading to increased expression of S1P1. Taken together, the present study highlights a unique and novel function of CCR2 signaling in the regulation of thymic egress.</p

Protective effects of Pt-N-C single-atom nanozymes against myocardial ischemia-reperfusion injury

Abstract Effective therapeutic strategies for myocardial ischemia/reperfusion (I/R) injury remain elusive. Targeting reactive oxygen species (ROS) provides a practical approach to mitigate myocardial damage following reperfusion. In this study, we synthesize an antioxidant nanozyme, equipped with a single-Platinum (Pt)-atom (PtsaN-C), for protecting against I/R injury. PtsaN-C exhibits multiple enzyme-mimicking activities for ROS scavenging with high efficiency and stability. Mechanistic studies demonstrate that the excellent ROS-elimination performance of the single Pt atom center precedes that of the Pt cluster center, owing to its better synergistic effect and metallic electronic property. Systematic in vitro and in vivo studies confirm that PtsaN-C efficiently counteracts ROS, restores cellular homeostasis and prevents apoptotic progression after I/R injury. PtsaN-C also demonstrates good biocompatibility, making it a promising candidate for clinical applications. Our study expands the scope of single-atom nanozyme in combating ROS-induced damage and offers a promising therapeutic avenue for the treatment of I/R injury