Rare Earth-Carbon Dots Nanocomposite-Modified Glass Nanopipettes: Electro-Optical Detection of Bacterial ppGpp.

As an important alarmone nucleotide, guanosine 3'-diphosphate-5'-diphosphate (ppGpp) can regulate the survival of bacteria under strict environmental conditions. Direct detection of ppGpp in bacteria with high sensitivity and selectivity is crucial for elucidating the role of ppGpp in bacterial stringent response. Herein, the terbium-carbon dots nanocomposite (CDs-Tb) modified glass nanopipet was developed for the recognition of ppGpp. The CDs-Tb in glass nanopipette preserved their fluorescence properties as well as the coordination capacity of Tb3+ toward ppGpp. The addition of ppGpp not only led to the fluorescence response of CDs-Tb but also triggered variations of surface charge inside the glass nanopipet, resulting in the ionic current response. Compared with nucleotides with similar structures, this method displayed good selectivity toward ppGpp. Moreover, the dual signals (fluorescence and ionic current) offered a built-in correction for potential interference. Apart from the high selectivity, the proposed method can determine the concentration of ppGpp from 10-13 to 10-7 M. Taking advantage of the significant analytical performance, we monitored ppGpp in Escherichia coli under different nutritional conditions and studied the relationship between ppGpp and DNA repair, which is helpful for overcoming antibiotic resistance and promoting the development of potential drugs for antibacterial treatment.

Glutathione S-transferase templated copper nanoclusters as a fluorescent probe for turn-on sensing of chlorotetracycline.

Hereby, facile-green copper nanoclusters templated by glutathione S-transferase (GST-CuNCs) have been innovatively synthesized via a simple one-pot stirring method at room temperature. The as-prepared nanoclusters exhibited uniform size with satisfactory fluorescence intensity, good stability and low cytotoxicity. Significantly, the fluorescence of the obtained GST-CuNCs could be considerably enhanced by the addition of chlorotetracycline (CTC) rather than other analogues of CTC, which was ascribed to the aggregation-induced enhancement caused by the interaction between CTC and GST. The enhanced fluorescence intensity demonstrated a good linear correlation with the CTC concentration in the range of 30-120 µM (R2 = 0.99517), and the low detection limit was 69.7 nM. Furthermore, the proposed approach showed favorable selectivity and anti-interference toward CTC among prevalent ions and amino acids. Additionally, this nanoprobe was also applied to the quantitative detection of CTC in serum samples with satisfactory outcomes, which demonstrated excellent prospects for practical applications.

Stimuli-responsive polymers for interface engineering toward enhanced electrochemical analysis of neurochemicals.

Neurochemical monitoring can provide important insights into the chemical communications in the brain and neurological diseases. Although electrochemical sensors have promoted the development of neurochemical analysis, the limited analytical performance of the existing sensors restrict our understanding of the roles that chemical signals play in the brain. The central nervous system is composed of a large number of neurochemical species. Meanwhile, it is difficult to monitor neurochemicals with high sensitivity because of the kinetic barrier of mass transport and electron/ion transfer. More importantly, to fabricate a "smart" electrochemical sensor for neurochemicals, the engineering of an electrode surface with switchable properties and a response is urgently needed. This review focuses on the construction and application of electrochemical sensors based on stimuli-responsive polymers. The response of polymers to external stimuli can not only enhance the target recognition, but also modulate the electrochemical signals, thus providing smart electrochemical sensing platform with improved analytical performance, including high selectivity, sensitivity, and controllability. In this review, we first introduce the design strategy of bio-responsive stimuli-responsive polymers and highlight the relationship between their structure and molecular recognition efficiency. Then, we summarize the electrochemical techniques with different sensing principles and emphasize the contribution that stimuli-responsive polymers made to the conversion of chemical/electrochemical reactions into electric signals. Finally, the opportunities and limitations of stimuli-responsive polymer-modified electrochemical sensors for neurochemical analysis will be discussed. Taking advantage of the development of novel materials, electrochemical techniques and microelectronic engineering, the advanced devices (e.g., antifouling, flexible, miniaturized, and multi-functional) with remarkable analytical performance will benefit the evaluation of neurochemicals, which can promote a deep understanding of brain events and the diagnosis and treatment of neurological diseases.

A highly sensitive and selective artificial nanochannel for in situ detection of hydroxyl radicals in single living cell.

As the most aggressive reactive oxygen species (ROS), hydroxyl radical (•OH) can directly modulate the biological ion channel and interfere with the progression of diseases. Inspired by biological •OH-activated ion channel, we reported a novel •OH-regulated glass nanopore functionalized with protoporphyrin Ⅸ (PP) film. This system showed outstanding •OH selective response owing to the ultra-fast reaction between •OH and thiol derivatives. In this case, the PP film is responsible for the changing not only of wettability but also of the inner surface charge. The synergetic effect of the dual transitions can regulate the ion transportation within the nanochannels and enabled tremendous enhancement of responsive efficiency. The detection limit could be achieved down to 1.58 nM. Taking advantage of the excellent analytical performance and mechanical qualities of this glass nanopore, the changes of •OH in single living cells were in situ monitored. Together, this study is beneficial for exploring the role of •OH in pathological events and shows promising potential for biomedical research.

The relationship between life events, life satisfaction, and coping style of college students.

We aimed to investigate the life events, life satisfaction, and coping style of college students, and to assess the relationship between them by performing mediating effect analysis. Our findings may provide a scientific basis for promoting the mental health of college students. Students in a medical college were selected using grade-stratified cluster sampling, and administered a standardized questionnaire survey. Out of 2,000 participants, 1827 participants provided valid questionnaires (response rate: 91.4%). The mean scores of life satisfaction and life events were 181.39 ± 30.28 and 19.32 ± 15.62, respectively. The mean score of coping style was 14.34 ± 7.54, which reflected positive coping style. Analysis of life satisfaction, life events, and factor scores showed that different grades, sibling status (whether the respondent was the only child in the family or not), family location, and life events had a significant association with life satisfaction (p < 0.001). There were significant differences in coping style between male and female students, and between students in different grades (p < 0.001). Positive coping style was found to play a partial mediating role between life events and life satisfaction, and the mediating effect accounted for 33.2% of the total effect. These results suggest that both life events and coping styles are related to college students' life satisfaction. The impact of life events on life satisfaction can be adjusted by psychological interventions to develop coping styles that can help promote the mental health of college students.

Rational design of a self-assembled surfactant film in nanopipettes: combined fluorescence and electrochemical sensing.

Herein, a generalizable method based on the formation of a self-assembled surfactant film was reported to build a nanopipette system. Using this nanopipette, it was found that arginine metabolism shows an age-related difference in Alzheimer's disease.

A highly selective ATP-responsive biomimetic nanochannel based on smart copolymer.

ATP-sensitive potassium (KATP) channels couple intracellular metabolism to the electrical activity by regulating K+ flux across the plasma membrane, thus playing an important role in both normal and pathophysiology. To understand the mechanism of ATP regulating biological ion channels, developing an ATP-responsive artificial nanochannel is an appealing but challenging topic because KATP channel is a heteromultimer of two subunits (potassium channel subunit (Kir6.x) and sulfonylurea receptor (SUR)) and exhibit dynamic functions with adjustability and reversibility. Inspired by the structure of KATP channels, we designed a smart copolymer modified nanochannel that may address the challenge. In the tricomponent poly(N-isopropylacrylamide) (PNIPAAm, PNI)-based copolymer system, phenylthiourea was used to bind the phosphate units of nucleotides and phenylboronic acid was introduced to combine the pentose ring of the nucleoside unit. Besides, a -COOH group with electron-withdrawing property was added into the phenylthiourea units, which may promote the hydrogen-bond-donating ability of thiourea. Specially, the smart copolymer not only provided static binding sites for recognition but also translated the recognition of ATP into their dynamic conformational transitions by changing the hydrogen-bonding environments surrounding PNIPAAm chains, thus achieving the gating function of nanochannel, which resembled the integration and coordination of Kir6.x and SUR units in active KATP. The ATP-regulated ion channel exhibited excellent stability and reversibility. This study is the first example showing how to learn from nature to assemble the ATP-responsive artificial nanochannel and demonstrate the possible mechanism of ATP gating.

Coordination of Ligand-Protected Metal Nanoclusters and Glass Nanopipettes: Conversion of a Liquid-Phase Fluorometric Assay into an Enhanced Nanopore Analysis.

We propose a unique concept for transforming the liquid-phase fluorometric assay into an enhanced nanopore analysis, which is based on the analyte binding-mediated changes in the surface chemistry of noble metal nanostructures in a confined space. In a proof-of-concept trial, the bovine serum albumin-protected gold nanoclusters (BSA-Au NCs) were designed as the sensing unit for biothiol determination. Through the specific interaction between biothiols and BSA-Au NCs, the validation system not only performed well in aqueous fluorescent detection but also can be developed into a more selective and sensitive nanopore sensor. In the confined space of the nanopore, the BSA-Au NC film with high density formed, and the addition of biothiols triggered the fluorescence enhancement as well as the ionic current response, hence leading to the construction of the dual-signal-output (fluorescence/ion current signal) system. The fluorescence signal proved that the ionic current change corresponded to the specific recognition process, improving the reliability of our nanopore method. Moreover, the ionic current response from the BSA-Au NC film can be used to quantify cysteine in a broad dynamic range of 0.001-1 pM with a detection limit as low as 1 fM. Such a strategy can be used to detect biothiols in complex biological fluids such as human serum. Therefore, the present work provided a new design strategy for a glass nanopipette sensor inspired by the principles of numerous and diverse fluorometric assays. It also sheds light on how the coupling of electrical and optical signals improves the accuracy, sensitivity, and selectivity of the glass nanopipette platform.

In situ detection of hydroxyl radicals in mitochondrial oxidative stress with a nanopipette electrode.

A novel nanopipette electrode was facilely constructed for the detection of ˙OH based on the inner surface wettability. The nanopipettes with excellent analytical performance were empolyed for in situ detection of ˙OH changes induced by mitochondrial oxidative stress and further utilized to study the association of ˙OH with Alzheimer's disease.

Interface engineering of microelectrodes toward ultrasensitive monitoring of ß-amyloid peptides in cerebrospinal fluid in Alzheimer's disease.

Ultrasensitive detection of monomeric ß-amyloid peptides is of fundamental significance for studying the pathological progression of Alzheimer's disease (AD). In this article, by facilely engineering a gold microelectrode interface, we developed a novel electrochemical biosensor for sensitive and selective monitoring of ß-amyloid peptide (Aß) monomers in cerebrospinal fluid (CSF). Through specific Cu2+-Aß-hemin coordination, Aß directed the assembly of Cu2+-PEI/AuNPs-hemin nanoprobes into network aggregates on a microelectrode interface, which promoted the enrichment of Aß monomers on the microelectrode. Furthermore, the AuNP aggregate promotes the deposition of silver nanoparticles, which were utilized for the electrochemical stripping analysis of the Aß monomer. The proposed method displayed ultra-sensitivity for Aß monomers with the detection limit down to 0.2 pM. Besides, high selectivity toward Aß monomers was observed. These remarkable analytical performances render the electrochemical biosensor useful for evaluating the dynamic change of Aß monomer level in CSF of live mice with AD, promoting the investigation of the role that Aß monomers play in brain events.

Sensitive and Selective Measurement of Hydroxyl Radicals at Subcellular Level with Tungsten Nanoelectrodes.

Hydroxyl radical (•OH) is an essential reactive oxygen species involved in critical cell functions. However, the mechanisms controlling its subcellular localization and intracellular level during health and disease remain poorly understood. This is due to the challenge of detecting •OH that are highly reactive and consequently short-lived (in vivo half-life of ∼10-9 s). Herein, we present tungsten nanoelectrodes functionalized with stable 1-hexanethiol (HAT) for selective and sensitive detection of •OH at the subcellular level via the destruction of the self-assembled monolayer of HAT on the nanoelectrode tip. Taking advantage of the ultrasmall nanotip and the super mechanical toughness, the tungsten nanoelectrode could easily penetrate a single living cell without inducing any observable damage. Controlled by a high precision micromanipulator, the •OH level in RAW 264.7 murine macrophages under amyloid ß (Aß) induced oxidative stress were first investigated by the nanoelectrodes at the subcellular level. Moreover, the results revealed the cordycepin-mediated cytoprotection of macrophages through modulation of PI3K/Akt pathway activity and introduction of heme oxygenase-1 (HO-1). We believe that the developed nanoelectrochemical method has shown great capacities for the study of potential drugs for therapeutic intervention of Alzheimer's disease.

The underlying characteristics of sleep behavior and its relationship to sleep-related cognitions: a latent class analysis of college students in Wuhu city, China.

The aim of this study was to gain insight into the sleep quality of college students and related factors from a new perspective by using Latent Class Analysis (LCA). A total of 1,288 college students from four universities in Wuhu city participated in the study. LCA was used to identify the classes of sleep behaviors. Differences in class membership related to selected research factors were examined using multinomial logistic regression analysis.Four distinct classes of behaviors were identified: (1) good sleep (Class 1, 31.8%), (2) prolonged sleep latency (Class 2, 49.1%), (3) sleep disturbances and daytime dysfunction (Class 3, 6.8%), (4) multiple poor sleep behavior (Class 4, 12.3%). The latent classes of sleep behavior were correlated with the DBAS-16 total score (rs = -0.109, P < 0.001). Learning pressure and mental state during the day could affect overall sleep (Class 2, Class 3 and Class 4), and female students were at higher risk of severe sleep problems (Class 3 and Class 4), while bedtime exercised could improve mild sleep problems (Class 2). The sleep behavior of college students in Wuhu city has obvious class heterogeneity, and different influencingfactors may affect sleep to varying degrees. In addition, our research provides a basis for targeted intervnetion in college student's sleep. .

Rational Design of Stimuli-Responsive Polymers Modified Nanopores for Selective and Sensitive Determination of Salivary Glucose.

The great pain and stress from finger-prick glucose measurements have resulted in great motivation to find noninvasive glucose monitoring technologies where salivary glucose measurement is desirable. However, the relative low concentration of glucose and coexisting chemicals in saliva challenges the sensitive and selective salivary glucose detection. In this article, we have rationally designed and constructed a salivary glucose sensor by modifying the inner wall of the Au-decorated glass nanopore with stimuli-responsive copolymer poly(3-(acryloylthioureido) phenylboronic acid-co-N-isopropylacrylamide) (denoted as PATPBA-co-PNIPAAm) via Au-S interaction. Notably, upon recognition of glucose, the copolymer could undergo a wettability switch and pKa shifts in the boronic acid functional groups, which significantly regulated the ion transport through nanopores, thus showing improved sensitivity with the detection limit of 1 nM. Moreover, benefiting from the multivalent boronic acid-glucose interaction and the cooperation of thiourea units, the copolymer exhibited good selectivity for glucose detection against the coexisting saccharides and other biological molecules in saliva. The nanopores with well-demonstrated analytical performance were finally applied for monitoring glucose in saliva. Together, this work unveiled a new platform for glucose detection in saliva, and promised to provide a new strategy for detecting other biomolecules in accessible biofluid involved in physiological and pathological events.

Food Handling Behaviors Associated with Reported Acute Gastrointestinal Disease That May Have Been Caused by Food.

Family food handling by women plays a key role in the risk of foodborne acute gastroenteritis. Nevertheless, the data indicating the association between women's food handling and foodborne disease has not been reported in the People's Republic of China. The purpose of this study was to determinate the status of food handling for women and the association between food handling behaviors and foodborne acute gastroenteritis. A cross-sectional survey was conducted from 1 September 2015 to 30 August 2016 in Anhui Province, China. Data on foodborne disease and food handling was collected via a questionnaire. Of the 630 respondents included in the study, 99 (16.0%) reported having experienced symptoms in the past 4 weeks of acute gastroenteritis that may have been caused by food. The following behaviors were prevalent in respondents: (i) infrequently boiling kitchen utensils to disinfect (70.6%); (ii) infrequently heating cooked food purchased from outside the home (64.3%); (iii) infrequently storing leftovers in the refrigerator (38.6%); and (iv) often purchasing stale raw vegetables, meat, and other ingredients (23.3%). Urban and rural respondents differed significantly in their answers to the food handling questions. Foodborne acute gastroenteritis was associated with the following behaviors: (i) infrequently heating milk (odds ratio [OR] = 2.587, 95% confidence interval [CI] = 1.396 to 6.458); (ii) infrequently heating leftovers stored in the refrigerator (OR = 16.967, 95% CI = 9.030 to 31.882); (iii) infrequently thoroughly heating kidney beans (OR = 3.524, 95% CI = 1.834 to 6.773); (iv) often storing raw and cooked meat in the same container (OR = 10.216, 95% CI = 5.109 to 20.431); and (v) often eating raw seafood (OR = 2.587, 95% CI = 1.424 to 4.700). Inappropriate food handling behaviors of women in the family are associated with foodborne acute gastroenteritis. Infrequent thorough heating and improper food storage are the most critical risk factors in foodborne acute gastroenteritis.

The correlation between family food handling behaviors and foodborne acute gastroenteritis: a community-oriented, population-based survey in Anhui, China.

BACKGROUND: Foodborne acute gastroenteritis is a significant public health concern. Food handling plays a key role in the risk of foodborne acute gastroenteritis. However, research focused on the correlation between foodborne acute gastroenteritis and food handling in the family environment is limited. The purpose of the current study was to determinate the association between food handling behaviors in the family environment and foodborne acute gastroenteritis. METHODS: A cross-sectional investigation was conducted from September 1, 2015 to August 30, 2016 in Anhui Province, China. A multistage stratified cluster sampling method was designed to select subjects. Data on foodborne acute gastroenteritis and food handling were collected via questionnaire survey. RESULTS: Of the 1516 subjects included in the study, 165 (10.9%) reported having experienced symptoms of foodborne acute gastroenteritis in the past 4 weeks. The following behaviors were more prevalent in those that experienced acute gastroenteritis: (1) infrequently thoroughly heating milk (75.6%); (2) infrequently thoroughly heating cooked food purchased from outside (71.3%); (3) infrequently thoroughly heating leftovers stored in the refrigerator (32.5%), and (4) infrequently storing leftovers in the refrigerator (41.6%). A multivariate logistic regression analysis found that foodborne acute gastroenteritis was associated with the following behaviors: (1) often eating raw seafood (P < 0.001, OR = 3.250, 95% CI = 2.136-4.946); (2) often storing raw meat and cooked meat in the same container (P < 0.001, OR = 4.291, 95% CI = 2.722-6.765); (3) infrequently thoroughly heating milk (P < 0.001, OR = 4.665, 95% CI = 2.526-8.617); (4) infrequently thoroughly heating leftovers stored in the refrigerator (P < 0.001, OR = 3.416, 95% CI = 2.139-5.454); (5) infrequently storing leftovers in the refrigerator (P < 0.05, OR = 1.775, 95% CI = 1.169-2.696); and (6) infrequently thoroughly cooking green beans (P < 0.001, OR = 2.859, 95% CI = 1.798-4.545). CONCLUSIONS: Poor food handling behaviors in the family environment are associated with foodborne acute gastroenteritis. Infrequent thorough heating and improper food storage are the most critical risk factors in foodborne acute gastroenteritis.

Investigation on dysfunctional beliefs and attitudes about sleep in Chinese college students.

OBJECTIVE: The aims of this study were to evaluate a subset of sleep-related cognitions and to examine whether dysfunctional beliefs and attitudes about sleep were associated with sleep quality in college students. PATIENTS AND METHODS: A total of 1,333 college students were enrolled in this study by randomized cluster sampling. A brief version of Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16) was administered to college students at several colleges. Sleep quality was also assessed using the Pittsburgh Sleep Quality Index (PSQI). The DBAS-16 scores were analyzed across different demographic variables, corresponding subscales of 7-item PSQI, and relevant sleep behavior variables. RESULTS: A total of 343 participants were poor sleepers, while 990 were good sleepers, as defined by PSQI. The DBAS-16 scores were lower in poor sleepers than in good sleepers (46.32 ± 7.851 vs 49.87 ± 8.349, p < 0.001), and DBAS-16 scores were lower in females and nonmedical students when compared with those in males and medical students, respectively (48.20 ± 8.711 vs 49.73 ± 7.923, p = 0.001; 48.56 ± 8.406 vs 49.88 ± 8.208, p = 0.009, respectively). The total score for sleep quality, as measured by PSQI, was negatively correlated with the DBAS-16 total score (r = -0.197, p < 0.01). There were significant differences in PSQI scores between individuals with attitudes and those without attitudes about sleep with respect to good sleep habits (p < 0.001), self-relaxation (p = 0.001), physical exercise (p < 0.001), taking sleeping pills (p = 0.004), and taking no action (p < 0.001). CONCLUSION: Dysfunctional beliefs about sleep are associated with sleep quality and should be discouraged, especially for females and nonmedical college students.

Association of Immune Factors with Drug-Resistant Tuberculosis: A Case-Control Study.

BACKGROUND Presently, studies of factors associated with drug-resistant tuberculosis (TB) focus on patients' socio-demographic characteristics and living habits, to the exclusion of biochemical indicators, especially immune factors. This study was carried out to determine whether immune factors are associated with drug-resistant TB. MATERIAL AND METHODS A total of 227 drug-resistant pulmonary TB patients and 225 drug-susceptible pulmonary TB patients were enrolled in this study. Information on socio-demographic characteristics and biochemical indicators were obtained through their clinical records. Non-conditional logistic regression was used to analyze the association of these indicators with drug-resistant TB. RESULTS There were significant differences in re-treatment, marital status, alanine aminotransferase (ALT), blood uric acid (BUA), carcino-embryonic antigen (CEA), T-spot, and CD3 and CD4 counts between the 2 groups. In multivariable analysis, re-treatment [Odds Ratio (OR)=5.290, 95% Confidence Interval [CI]=2.652-10.551); CD3 (OR=1.034, 95% CI=1.001-1.068); CD4 (OR=1.035, 95% CI =1.001-1.070) and IgM (OR=1.845, 95% CI=1.153-2.952) were associated with drug-resistant TB. CONCLUSIONS These results suggest the need for greater attention to re-treatment cases and immune function when treating drug-resistant TB.

Gender differences in factors associated with smartphone addiction: a cross-sectional study among medical college students.

BACKGROUND: Smartphones are becoming increasingly indispensable in everyday life for most undergraduates in China, and this has been associated with problematic use or addiction. The aim of the current study was to investigate the prevalence of smartphone addiction and the associated factors in male and female undergraduates. METHODS: This cross-sectional study was conducted in 2016 and included 1441 undergraduate students at Wannan Medical College, China. The Smartphone Addiction Scale short version (SAS-SV) was used to assess smartphone addiction among the students, using accepted cut-offs. Participants' demographic, smartphone usage, and psycho-behavioral data were collected. Multivariate logistic regression models were used to seek associations between smartphone addiction and independent variables among the males and females, separately. RESULTS: The prevalence of smartphone addiction among participants was 29.8% (30.3% in males and 29.3% in females). Factors associated with smartphone addiction in male students were use of game apps, anxiety, and poor sleep quality. Significant factors for female undergraduates were use of multimedia applications, use of social networking services, depression, anxiety, and poor sleep quality. CONCLUSIONS: Smartphone addiction was common among the medical college students investigated. This study identified associations between smartphone usage, psycho-behavioral factors, and smartphone addiction, and the associations differed between males and females. These results suggest the need for interventions to reduce smartphone addiction among undergraduate students.

Biomimetic Mineralization of Gold Nanoclusters as Multifunctional Thin Films for Glass Nanopore Modification, Characterization, and Sensing.

Hurdles of nanopore modification and characterization restrain the development of glass capillary-based nanopore sensing platforms. In this article, a simple but effective biomimetic mineralization method was developed to decorate glass nanopore with a thin film of bovine serum albumin-protected Au nanocluster (BSA-Au NC). The BSA-Au NC film emitted a strong red fluorescence whereby nondestructive characterization of Au film decorated at the inner surface of glass nanopore can be facilely achieved by a fluorescence microscopy. Besides, the BSA molecules played dual roles in the fabrication of functionalized Au thin film in glass nanopore: they not only directed the synthesis of fluorescent Au thin film but also provided binding sites for recognition, thus achieving synthesis-modification integration. This occurred due to the ionized carboxyl groups (-COO-) of a BSA coating layer on Au NCs which can interacted with arginine (Arg) via guanidinium groups. The added Arg selectively led to the change in the charge and ionic current of BSA-Au NC film-decorated glass nanopore. Such ionic current responses can be used for quantifying Arg with a detection limit down to 1 fM, which was more sensitive than that of previous sensing systems. Together, the designed method exhibited great promise in providing a facile and controllable solution for glass nanopore modification, characterization, and sensing.

Rational Design of a Stimuli-Responsive Polymer Electrode Interface Coupled with in Vivo Microdialysis for Measurement of Sialic Acid in Live Mouse Brain in Alzheimer's Disease.

Sensitive and selective monitoring of sialic acid (SA) in cerebral nervous system is of great importance for studying the role that SA plays in the pathological process of Alzheimer's disease (AD). In this work, we first reported an electrochemical biosensor based on a novel stimuli-responsive copolymer for selective and sensitive detection of SA in mouse brain. Notably, through synergetic hydrogen-bonding interactions, the copolymer could translate the recognition of SA into their conformational transition and wettability switch, which facilitated the access and enrichment of redox labels and targets to the electrode surface, thus significantly improving the detection sensitivity with the detection limit down to 0.4 pM. Besides amplified sensing signals, the proposed method exhibited good selectivity toward SA in comparison to potential interference molecules coexisting in the complex brain system due to the combination of high affinity between phenylboronic acid (PBA) and SA and the directional hydrogen-bonding interactions in the copolymer. The electrochemical biosensor with remarkable analytical performance was successfully applied to evaluate the dynamic change of SA level in live mouse brain with AD combined with in vivo midrodialysis. The accurate concentration of SA in different brain regions of live mouse with AD has been reported for the first time, which is beneficial for progressing our understanding of the role that SA plays in physiological and pathological events in the brain.