Development of Electrochemical Sensors Suitable for In Vivo Detection for Neurotransmitters

The electrochemical method of redox cycling was exploited to achieve new discoveries in neurotransmitter detection and to advance its suitability toward in vivo use. Redox cycling has advantages in signal amplification, selectivity of species based on their electrochemical reaction mechanisms, and limited or no background subtraction. Distinction of dopamine from norepinephrine in a mixture with an electrochemical method at unmodified electrodes was demonstrated for the first time in vitro. This ability resulted from a series of fundamental studies of redox cycling behavior of the catecholamines (dopamine, norepinephrine and epinephrine) using different electrode configurations. Taking advantage of the ECC’ mechanism associated with their electrochemical oxidation and the substantially different rate constants for the first order intramolecular cyclization reaction, the catecholamines can be distinguished by monitoring the current at collector electrodes activated at different distances from the generator. In vitro detection of dopamine in the presence of multiple electrochemically-active interfering species (ascorbic acid, uric acid, L 3,4 dihydroxyphenylalanine, homovanillic acid, 3 methoxytyramine and 5 hydroxyindoleacetic acid) has also been investigated for future in vivo applications. Selective detection of physiological concentrations of dopamine at the collector electrodes using microfabricated electrode arrays was shown (with detection limits of 0.730 ± 0.013 µM and 0.086 ± 0.002 µM for dopamine with and without the presence of interfering species, respectively). In addition, two types of unique neural probes (co-planar and vertical edge microelectrode arrays) were designed with the purpose to implement the redox cycling approach in vivo. An innovative design was used to minimize the number of masks for eight layers of electrodes. Different microfabrication procedures were evaluated, with further work still needed for optimization. Also, analysis of anodic stripping voltammetry of silver-containing nanoparticles modified on electrode surfaces, performed as an interest in expanding the detection to other important neurochemicals, showed that commonly used drop-casting techniques deposit nanoparticles non-uniformly. More reproducible modification methods are needed. The work in this dissertation demonstrates the capabilities of redox cycling for multi-neurotransmitter analysis and sets the foundation for development of novel neural probes for implementing the approach. This method may also be used to obtain mechanisms and kinetics beyond the ones investigated here

Electrochemical hydrogenation of mixed-phase TiO₂ nanotube arrays enables remarkably enhanced photoelectrochemical water splitting performance

We first report that photoelectrochemical (PEC) performance of electrochemically hydrogenated TiO2 nanotube arrays (TNTAs) as high-efficiency photoanodes for solar water splitting could be well tuned by designing and adjusting the phase structure and composition of TNTAs. Among various TNTAs annealed at different temperature ranging from 300 to 700 °C, well-crystallized single anatase (A) phase TNTAs-400 photoanode shows the best photoresponse properties and PEC performance due to the favorable crystallinity, grain size and tubular structures. After electrochemical hydrogenation (EH), anatase-rutile (A-R) mixed phase EH-TNTAs-600 photoanode exhibits the highest photoactivity and PEC performance for solar water splitting. Under simulated solar illumination, EH-TNTAs-600 achieves the best photoconversion efficiency of up to 1.52% and maximum H2 generation rate of 40.4 µmol h−1 cm−2, outstripping other EH-TNTAs photoanodes. Systematic studies reveal that the signigicantly enhanced PEC performance for A-R mixed phaes EH-TNTAs-600 photoanode could be attributed to the synergy of A-R mixed phases and intentionally introduced Ti3+ (oxygen vacancies) which enhances the photoactivity over both UV and visible-light regions, and boosts both charge separation and transfer efficiencies. These findings provide new insight and guidelines for the construction of highly efficient TiO2-based devices for the application of solar water splitting.This work was supported by the National Natural Science Foundation of China (51402078, 21702041, and 11674354), the National Basic Research Program of China (2014CB660815), and the Fundamental Research Funds for the Central Universities (JZ2016HGTB0711, JZ2016HGTB0719, and JZ2017HGPA0167)

Microfluidic Device for On-Chip Immunophenotyping and Cytogenetic Analysis of Rare Biological Cells

This work is licensed under a Creative Commons Attribution 4.0 International License.The role of circulating plasma cells (CPCs) and circulating leukemic cells (CLCs) as biomarkers for several blood cancers, such as multiple myeloma and leukemia, respectively, have recently been reported. These markers can be attractive due to the minimally invasive nature of their acquisition through a blood draw (i.e., liquid biopsy), negating the need for painful bone marrow biopsies. CPCs or CLCs can be used for cellular/molecular analyses as well, such as immunophenotyping or fluorescence in situ hybridization (FISH). FISH, which is typically carried out on slides involving complex workflows, becomes problematic when operating on CLCs or CPCs due to their relatively modest numbers. Here, we present a microfluidic device for characterizing CPCs and CLCs using immunofluorescence or FISH that have been enriched from peripheral blood using a different microfluidic device. The microfluidic possessed an array of cross-channels (2–4 µm in depth and width) that interconnected a series of input and output fluidic channels. Placing a cover plate over the device formed microtraps, the size of which was defined by the width and depth of the cross-channels. This microfluidic chip allowed for automation of immunofluorescence and FISH, requiring the use of small volumes of reagents, such as antibodies and probes, as compared to slide-based immunophenotyping and FISH. In addition, the device could secure FISH results in <4 h compared to 2–3 days for conventional FISH

Positive response to trastuzumab deruxtecan in a patient with HER2-mutant NSCLC after multiple lines therapy, including T-DM1: a case report

Human epidermal growth factor 2 (HER2) mutations are uncommon in non-small cell lung cancer (NSCLC), and the lack of established, effective, targeted drugs has resulted in a persistently poor prognosis. Herein, we report the case of a non-smoking, 58-year-old man diagnosed with lung adenocarcinoma (cT3N0M1c, stage IVB) harboring a HER2 mutation (Y772_A775dupYVMA) and PD-L1 (-). The patient’s Eastern Cooperative Oncology Group performance status (PS) score was assessed as 1. He commenced first-line treatment with chemotherapy, followed by immuno-chemotherapy, and with disease progression, he received HER2-targeted therapy and chemotherapy with an anti-angiogenic agent. However, HER2-targeted therapy, including pan-HER tyrosine kinase inhibitors (afatinib, pyrotinib, and pozitinib) and antibody–drug conjugate (T-DM1), produced only stable disease (SD) as the best response. After the previously described treatment, primary tumor recurrence and multiple brain metastases were observed. Despite the patient’s compromised overall physical condition with a PS score of 3-4, he was administered T-DXd in addition to whole-brain radiotherapy (WBRT). Remarkably, both intracranial metastases and primary lesions were significantly reduced, he achieved a partial response (PR), and his PS score increased from 3-4 to 1. He was then treated with T-DXd for almost 9 months until the disease again progressed, and he did not discontinue the drug despite the occurrence of myelosuppression during this period. This is a critical case as it exerted an effective response to T-DXd despite multiple lines therapy, including T-DM1. Simultaneously, despite the occurrence of myelosuppression in the patient during T-DXd, it was controlled after aggressive treatment

Combined miRNA and mRNA sequencing reveals the defensive strategies of resistant YHY15 rice against differentially virulent brown planthoppers

IntroductionThe brown planthopper (BPH) poses a significant threat to rice production in Asia. The use of resistant rice varieties has been effective in managing this pest. However, the adaptability of BPH to resistant rice varieties has led to the emergence of virulent populations, such as biotype Y BPH. YHY15 rice, which carries the BPH resistance gene Bph15, exhibits notable resistance to biotype 1 BPH but is susceptible to biotype Y BPH. Limited information exists regarding how resistant rice plants defend against BPH populations with varying levels of virulence.MethodsIn this study, we integrated miRNA and mRNA expression profiling analyses to study the differential responses of YHY15 rice to both avirulent (biotype 1) and virulent (biotype Y) BPH.ResultsYHY15 rice demonstrated a rapid response to biotype Y BPH infestation, with significant transcriptional changes occurring within 6 hours. The biotype Y-responsive genes were notably enriched in photosynthetic processes. Accordingly, biotype Y BPH infestation induced more intense transcriptional responses, affecting miRNA expression, defenserelated metabolic pathways, phytohormone signaling, and multiple transcription factors. Additionally, callose deposition was enhanced in biotype Y BPH-infested rice seedlings.DiscussionThese findings provide comprehensive insights into the defense mechanisms of resistant rice plants against virulent BPH, and may potentially guide the development of insect-resistant rice varieties

Application of Electrochemical Redox Cycling: Toward Differentiation of Dopamine and Norepinephrine

The electrochemical redox cycling behavior of dopamine (DA), norepinephrine (NE), and their mixture was investigated using coplanar gold microband electrode arrays at four generator-collector gap conditions (4, 12, 20, and 28 μm). This method provides opportunity for differentiating the catecholamines in mixtures by monitoring the current at collector electrodes activated at different distances from generator electrodes. It takes advantage of the ECC′ mechanism associated with the electrochemical oxidation of catecholamines, in which DA and NE have rate constants that differ by a factor of 7.5 for the first order intramolecular cyclization (C) following electron transfer (E). Collector electrodes activated at different distances from the generators were used to examine the process of the following chemistry at different time points, because spatial relationships are related to temporal ones through diffusion. Solutions of artificial cerebral spinal fluid containing 50 μM DA, 50 μM NE, and a DA–NE mixture of 50 μM of each were examined. The collection efficiency during redox cycling for NE had a greater dependence on gap width than DA, and the collector current of NE became silent at ∼20 μm. The collector current of the mixture approaches that of DA alone with increasing gap, suggesting that differentiation of DA and NE may be possible. The collector current of the mixture is further affected by the homogeneous reaction (C′) between oxidized and cyclized products of DA and NE and drops below that of DA alone. This may be used for differentiation in more complicated chemical systems

Authentication-Based Vehicle-to-Vehicle Secure Communication for VANETs

Communication in VANETs is vulnerable to various types of security attacks since it is constructed based on an open wireless connection. Therefore, a lightweight authentication (LIAU) scheme for vehicle-to-vehicle communication is proposed in this paper. The LIAU scheme requires hash operations and uses cryptographic concepts to transfer messages between vehicles, in order to maintain the required security. Moreover, we made the LIAU scheme lightweight by introducing a small number of variable parameters in order to reduce the storage space. Performance analysis shows that the LIAU scheme is able to resist various types of security attacks and it performs well in terms of communication cost and operation time

Multiple Bismuth Quadruple Therapy Containing Tetracyclines Combined with Other Antibiotics and <i>Helicobacter pylori</i> Eradication Therapy

Helicobacter pylori (HP) infection is closely associated with the development of chronic gastritis, peptic ulcer, and gastric cancer. However, the resistance rate of H. pylori strains to antibiotics such as clarithromycin, metronidazole, and levofloxacin has increased significantly, resulting in a significant decrease in the eradication efficacy of commonly used regimens. Tetracycline has received the attention of domestic and foreign scholars because of its low resistance. The purpose of this review is to provide an update on the tetracycline-containing bismuth quadruple eradication therapy for H. pylori infection and review the efficacy and safety of the regimens, hoping to provide guidance for clinical practice

Effect of Welding Sequence and the Transverse Geometry of the Weld Overlay on the Distribution of Residual Stress in the Weld Overlay Repair of T23 Tubes

Water-wall tubes are important components in power plants and are used to absorb the heat from the boilers, and they often fail prematurely due to corrosion, erosion, and fatigue during service. To repair the defects, weld overlay repair is often adopted by forming a compressive stress area around the susceptible area to prevent the cracks from propagating. In order to obtain reasonable process parameters of weld overlay repair, a study combining experiments and numerical simulations was performed to investigate the welding residual stress distribution on the repaired area with different welding repair methods. The results reveal that a compressive stress area is generated on the repaired area after the repair, and a center-to-outside welding sequence is better than either a right-to-left welding sequence or an outside-to-center welding sequence when overlaying a one-layer weld; with an increase in the number of weld layers, the compressive stress area of the repaired area is expanded, and the stress level is increased, which results from the upward movement of the compressive stress area of the subsequent-overlaying layer and the superposition of the compression areas of the subsequent-overlaying layer and previous-overlaying layer, respectively. In addition, the number of the weld passes of each layer should be not less than four with the center-to-outside welding sequence

Inpatient Satisfaction with Nursing Care and Its Impact Factors in Chinese Tertiary Hospitals: A Cross-Sectional Study

Aims: To evaluate the level of patient satisfaction with nursing care in China&rsquo;s major tertiary hospitals, and to explore patient and hospital level factors associated with patient satisfaction, in order to provide policy implications for the evaluation and improvement of nursing care, toward a patient-centered healthcare system. Background: Patient satisfaction with nursing care has been designated as a key measure of the quality of nursing care and is one of the main focuses of the current healthcare improvement campaign in China. Methods: We participated in the 2021 China National Patient Survey and designed and administered a survey instrument with five domains, to evaluate patient satisfaction with nursing care among 24,971 inpatients from 143 tertiary hospitals across 31 provinces in China. Descriptive analysis and binary logistic regressions were utilized to assess the level of satisfaction and identify key factors related to nursing satisfaction. Results: The overall satisfaction level is high, but satisfaction with health guidance is relatively low. Patients&rsquo; sociodemographic characteristics, including age, income, and education, are significantly associated with their satisfaction. Hospital characteristics, such as geographic location, type, and nurse-to-doctor ratio, significantly impact inpatient satisfaction with nursing care. Patients of hospitals in the eastern region, general hospitals, and hospitals with higher nurse-to-doctor ratios are more satisfied with nursing care. Conclusion: More attention should be paid to equitably allocating healthcare resources among different regions, improving the management and competence of non-general hospitals, and strengthening the recruitment and retention of the nursing workforce. Moreover, patient characteristics should be considered when evaluating patient satisfaction across hospitals. Patient and Public Contribution: These findings will help us better understand patients&rsquo; satisfaction regarding nursing care in Chinese tertiary hospitals and develop targeted interventions, to establish a patient-centered healthcare system