Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.

GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential.

Distinguishable Magnetic Reporter Coordination with Buoyancy-Magnetism Separation for Immobilization-Free Dual-Target Electrochemical Immunosensing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study.

BACKGROUND: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. METHODS: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. RESULTS: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). CONCLUSIONS: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

A perylene diimide electrochemical probe with persulfate as a signal enhancer for dopamine sensing.

Dopamine (DA) is an important biomarker related to parkinsonism, schizophrenia and renal disease. Traditional electrochemical sensors for DA were based on the direct electrochemical oxidation of DA. In this paper, we report a new sensing strategy using N,N'-di(trimethylaminoethyl)perylene diimide (TMPDI) as an electrochemical probe and K2S2O8 as a signal enhancer for DA detection between 0 and -0.7 V with the DPV technique. MoS2 nanoflowers prepared by the hydrothermal method were used as a nanocarrier to load TMPDI. The reduction current of TMPDI was found to show a stepwise and significant increase at -0.24 V with the increase of concentration of K2S2O8 due to the continuous cycle of TMPDI molecules' electrochemical reduction and chemical oxidation. The presence of DA caused a large decrease of the reduction current of TMPDI due to the synergistic interaction of the competitive consumption of DA for K2S2O8 and the blocking effect of polyDA adhering to the electrode surface. The decreased current exhibited a linear response for DA from 10 pM to 100 µM with a detection limit of 4.1 pM and the proposed sensor showed high selectivity and excellent feasibility in human urine/serum sample detection.

The intake of solid fat and cheese may be associated with a reduced risk of Helicobacter pylori infection status: a cross-sectional study based on NHANES 1999-2000.

BACKGROUND: Diet plays an important role in Helicobacter pylori (HP) infection, and our objective was to investigate potential connections between dietary patterns, specific food groups, and HP infection status in U.S. adults. METHODS: The data for this study was obtained from the NHANES (National Health and Nutrition Survey) database for the year 1999-2000. This cross-sectional study involved the selection of adults aged 20 years and older who had undergone dietary surveys and HP testing. Factor analysis was employed to identify dietary patterns, and logistic regression models were utilized to assess the association between these dietary patterns and specific food groups with HP infection status. RESULT: Based on the inclusion and exclusion criteria, our final analysis included 2,952 individuals. The median age of participants was 51.0 years, and 48.7% were male. In the study population, the overall prevalence of HP infection was 44.9%. Factor analysis revealed three distinct dietary patterns: High-fat and high-sugar pattern (including solid fats, refined grains, cheese, and added sugars); Vegetarian pattern (comprising fruits, juices, and whole grains); Healthy pattern (encompassing vegetables, nuts and seeds, and oils). Adjusted results showed that the high-fat and high-sugar pattern (OR = 0.689, 95% CI: 0.688-0.690), vegetarian pattern (OR = 0.802, 95% CI: 0.801-0.803), and healthy pattern (OR = 0.717, 95% CI: 0.716-0.718) were all linked to a lower likelihood of HP infection. Further analysis of the high-fat and high-sugar pattern revealed that solid fats (OR = 0.717, 95% CI: 0.716-0.718) and cheese (OR = 0.863, 95% CI: 0.862-0.864) were protective factors against HP infection, while refined grains (OR = 1.045, 95% CI: 1.044-1.046) and added sugars (OR = 1.014, 95% CI: 1.013-1.015) were identified as risk factors for HP infection. CONCLUSION: Both the Vegetarian pattern and the Healthy pattern are associated with a reduced risk of HP infection. Interestingly, the High-fat and High-sugar pattern, which is initially considered a risk factor for HP infection when the score is low, becomes a protective factor as the intake increases. Within this pattern, animal foods like solid fats and cheese play a protective role, while the consumption of refined grains and added sugars increases the likelihood of HP infection.

Development and preliminary evaluation of the Comprehensive Health Self-Assessment Questionnaire (CHSAQ) for individuals in the Chinese People Liberation Army.

OBJECTIVE: There is currently no widely accepted multidimensional health assessment questionnaire for individuals in the Chinese People Liberation Army (PLA). This study developed a multidimensional health survey questionnaire (Comprehensive Health Self-Assessment Questionnaire, CHSAQ) suitable for personnel in the PLA and conducted a preliminary examination of its reliability, validity, and discriminative ability. METHODS: After 183 items from 32 dimensions were selected to form the initial version of the CHSAQ, three groups of soldiers were selected from May 2022 to April 2023 and completed three survey rounds (with 183, 131, and 55 valid items). The items were screened based on classic test theory. After screening, the final questionnaire entries were formed, the structure of the questionnaire was explored through exploratory factor analysis and confirmatory factor analysis, and its reliability, structural validity, and discriminative ability were evaluated. RESULTS: The final questionnaire consisted of 8 dimensions and 55 items on job satisfaction, anxiety and depression, daily activities, physical function, the otolaryngology system, the integumentary system, sleep disorders, and the visual system. The total cumulative variance contribution rate was 64.648% according to exploratory factor analysis. According to the confirmatory factor analysis, the normed fit index (NFI) was 0.880, and the comparison fit index (CFI) was 0.893 (close to 0.90). The Cronbach's α coefficient of the total questionnaire was 0.970, the split half reliability coefficient was 0.937, and the retest reliability coefficient was 0.902. The results are presented as different pairwise comparisons. CONCLUSION: Our study developed a self-report questionnaire for evaluating the comprehensive health status of personnel in the PLA in accordance with the standard procedure for questionnaire development. Our findings also showed that the CHSAQ for individuals in the PLA has good reliability and structural validity.

Performance and micro-pacing in sprint cross-country skiing: A comparison of individual time-trial and head-to-head race formats.

This study compared performance strategies and sub-technique selection in cross-country skate skiing sprint races, specifically individual time-trial (ITT) and head-to-head (H2H) formats. Fourteen male cross-country skiers from the Chinese national team participated in the FIS-sanctioned sprint race day. GNSS and heart rate sensors recorded positioning, skiing speeds, heart rate, sub-technique usage, and skiing kinematics. Statistical parametric mapping (SPM) was used to determine the course positions (clusters) where instantaneous skiing speed was significantly associated with section time. One-way analyses of variance were used to examine differences between the ITT and H2H. H2H race speeds were 2.4 ± 0.2% faster than the ITT race (p < 0.05).Variations in sub-technique and skiing kinematics were observed between race formats, indicating different strategies and tactics employed by athletes. SPM identified specific clusters (primarily uphill) where the fastest athlete gained significant time over the slowest. The greatest time gains were associated with higher G3 sub-technique usage and longer G3 cycle length on steep uphill terrain (9-13% gradients). Integrating SPM analyses and sub-technique assessments can help optimise performance and tactics in sprint races. This study enhances our understanding of cross-country skiing dynamics and performance variations among elite competitors.

First report of Lasiodiplodia pseudotheobromae causing soft rot of plum in China.

Plum (Prunus salicina) is one of the most important fruit tree species worldwide (Valderrama-Soto et al. 2021). In June 2023, the postharvest soft rot symptoms were observed on plum fruits in several fruit markets of Guiyang city, Guizhou province, China. The disease incidence in these markets ranged from 20 to 25% with 70% disease severity. Plum fruits showed rotting, which was characterized by water soaked fruit tissue, softening and presence of whitish mycelia four days post inoculation. In severe conditions, whole fruits become rotted and were covered with white fungal mycelia. Small sections (5 × 3 mm) from 6 diseased plum fruits were surface sterilized by using 75% ethanol for 30 s followed by 0.1% mercuric chloride solution for 5 min, rinsed three times with ddH2O, and then transferred onto potato dextrose agar (PDA) and incubated at 25 ± 2°C for three days. Three pure cultures (GUCC23-0001 to GUCC23-0003) were obtained by transferring a single hyphal tip to new PDA plates. Colonies of these isolates were grayish-white initially, gradually turning to whitish brown with fluffy aerial mycelia and uneven edges and finally turned to a dark gray colony after five days of inoculation. The pseudoparaphyses were hyaline, cylindrical, aseptate, and rounded at apex. Conidia were ellipsoidal, hyaline, unicellular, and 24.2 to 28.6 × 12.3 to 15.5 µm in size (n = 30) (Fig. S1), which were similar to the morphology of Lasiodiplodia pseudotheobromae (Alves et al. 2008). Furthermore, fungal DNA was extracted from fresh mycelia of PDA after seven days by using fungus genomic DNA extraction kit (Biomiga, USA). Partial DNA sequences from four loci including internal transcribed spacer (ITS), translation elongation factor 1-alpha (tef1), beta-tubulin (tub2), and polymerase II second largest subunit (rpb2) were amplified with ITS1 and ITS4 (White et al. 1990), EF1-688F and EF1-1251R (Alves et al. 2008), Bt2a and Bt2b (Glass and Donaldson 1995), and RPB2-LasF and RPB2-LasR, respectively (Cruywagen et al. 2017). GenBank accession numbers are OR361680, OR361681, OR361682 for ITS, OR423394, OR423395, OR423396 for tef1, OR423397, OR423398, OR423399 for tub2, and OR423391, OR423392, OR423393 for rpb2, and gene sequencing showed 99.6 to 100% identity with ex-type strain of L. pseudotheobromae (CBS 116459). Phylogenetic analysis also placed our isolates in a highly supported clade with the reference isolate of L. pseudotheobromae (Fig. S2). Another experiment was designed to confirm the pathogenicity test for additional confirmation. Five mm mycelial plugs of L. pseudotheobromae from a three day old culture on PDA were placed on five surface-sterilized and non-wounded plum fruits for 12 hours and incubated at 25°C ± 2°C for four days. Sterilized fungus free PDA plugs were used as a negative control. Mycelial plugs were removed after 12 hours following which whole fruits were incubated in plastic boxes at 25°C ± 2°C. The experiment was repeated twice. The pathogenicity was evaluated under control conditions in laboratory (relative humidity, 70 ± 5% and temperature 25 ± 5˚C). Plum fruits showed rotting, which was characterized by water soaked fruit tissue, softening and presence of whitish mycelia four days post inoculation. These symptoms and signs were similar to the initially observed symptoms on plums in the markets. No disease symptoms were observed on the control fruits. The re-isolated fungus obtained from inoculated plum fruits was very similar to those isolated from diseased samples in morphology, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of L. pseudotheobromae causing postharvest fruit rot of plum in China. In 2022, the total planting area of plum was 1946.5 thousand hectares, which produces approximately 6626300 tons of plum (Food and Agriculture Organization of the United Nations, 2022). Based on the disease incidence and severity reported in the current study, soft rot of plum may be responsible for nearly 35% of yield losses under severe. Therefore, our study laid a theoretical foundation for the prevention and control of this post-harvest disease of plum.

A novel dual-signal output strategy for POCT of CEA based on a smartphone electrochemical aptasensing platform.

A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H2O2. Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr-O-P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H2O2. At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H2O2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL-1 to 100 ng·mL-1 and low detection limits of 0.98 pg·mL-1 and 0.27 pg·mL-1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring.

Assessing attitudes towards biostatistics education among medical students: adaptation and preliminary evaluation of the Chinese version survey of attitudes towards statistics (SATS-36).

BACKGROUND: Despite the numerous advantages of mastering biostatistics, medical students generally perceive biostatistics as a difficult and challenging subject and even experience anxiety during the courses. Evidence for the correlation between students' academic achievements and their attitudes, indicating that attitudes at the beginning of the biostatistics course may affect cognitive competence at the end of the course and subsequently influence student academic performance. However, there are current disagreements regarding the measurement and evaluation of attitudes related to statistics. Thus, there is a need for standard instruments to assess them. This study was conducted to develop a Chinese version of the Survey of Attitudes Toward Statistics (SATS-36) in order to acquire a valid instrument to measure medical students' attitudes toward biostatistics under Chinese medical educational background. METHODS: The Chinese version SATS-36 was developed through translation and back-translation of the original scale, with subsequent revisions based on expert advice to ensure the most appropriate item content. The local adaption was performed with a cohort of 1709 Chinese-speaking medical undergraduate and graduate students enrolled in biostatistics courses. And then, the reliability, validity and discrimination of the questionnaires were evaluated through correlation coefficient calculation, factor analysis, parallel analysis and other methods. RESULTS: The Chinese version SATS-36 consisted of 36 items and loaded a five-factor structure by factor analysis, which offered an alternative similar but not equal to that original six-factor structure. The cumulative variance contribution rate was 62.20%, the Cronbach's α coefficient was 0.908, the Guttman split-half reliability coefficient was 0.905 and the test-retest reliability coefficient was 0.752. Discriminant analysis revealed small to large significant differences in the five attitude subscales. CONCLUSIONS: The Chinese version SATS-36 with good validity and reliability in this study can be used to evaluate the learning framework of Chinese medical students.

Modified endoscopic retrograde appendicitis therapy vs. laparoscopic appendectomy for uncomplicated acute appendicitis in children.

OBJECTIVES: Modified endoscopic retrograde appendicitis therapy (mERAT) has been proposed as an alternative to laparoscopic appendectomy for the treatment of appendicitis. However, data from children in large samples are lacking. The aim of this article is to evaluate the efficacy between mERAT and laparoscopic appendectomy (LA) in children with uncomplicated appendicitis. METHOD: We retrospectively analyzed 594 patients with suspected uncomplicated appendicitis from October 2018 to May 2021. A pool of 294 consecutive patients who met the inclusion criteria were ultimately enrolled in this study (228 and 66 patients in mERAT and LA, respectively). Given the differences in baseline clinical data (gender, age), the regression equation including differences in clinical baseline, grouping factor, and white blood cell count was established to address the influence of potential confounding factors. RESULT: The initial success rate of mERAT management was 96.9%, and the recurrence rate was 6.9% in the mERAT group and 1.7% in the LA group within 1 year, which was no significant difference. But the mERAT group had a lower rate of adverse events. Finally, those results indicated that the treatment modalities, LA or mERAT, had no significant effect on initial success rate (P = 0.99) or recurrence rate (P = 0.17) within 1 year, but a significant effect on the adverse events rate during hospitalization (P = 0.01) in the multivariate regression analysis. CONCLUSION: Among children with uncomplicated appendicitis, an initial mERAT management strategy had a success rate of 96.9%, which was similar to the LA group at 1 year. This follow-up supports the feasibility of mERAT alone as an alternative to surgery for uncomplicated appendicitis.

Psychometric Properties of the Brief Pain Inventory Among Patients With Osteoarthritis Undergoing Total Knee Arthroplasty Surgery.

BACKGROUND: Knee osteoarthritis (OA) is characterized by pain and functional restrictions, necessitating precise and reliable pain evaluation for effective disease surveillance and postoperative treatment appraisal. METHODS: This investigation recruited 110 participants who were slated to receive unilateral total knee arthroplasty (TKA) and administered 3 self-reported questionnaires: the Brief Pain Inventory (BPI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 5-level EuroQoL Group's 5-dimension questionnaire (EQ-5D-5L), at baseline and 1 year after surgery. Using standard statistical methods and indicators, the BPI was subjected to a battery of psychometric evaluations, including assessments of reliability, validity, and responsiveness. RESULTS: At baseline, there were no significant ceiling or floor effects observed. Additionally, the internal consistency reliability (Cronbach's alpha) of the BPI was above 0.8, suggesting that the questionnaire items are adequately related to one another. The study found moderate to very strong correlations between the pain and physical function domains of the BPI and Western Ontario and McMaster Universities Osteoarthritis Index, as well as a strong correlation between the functional interference dimension of the BPI and the EQ-5D, supporting the construct validity of the BPI. Also, the BPI was found to be responsive to changes in pain over time, with a responsiveness index ranging from 2.55 to 3.19. CONCLUSION: The BPI assessment tool demonstrated good reliability, validity, and responsiveness in knee osteoarthritis patients who have undergone TKA and can be a useful measurement tool in clinical research to evaluate the effectiveness of pain management strategies and surgical interventions.

Fascinating Immobilization-Free Electrochemical Immunosensing Strategy Based on the Cooperation of Buoyancy and Magnetism.

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.

Risk prediction of preoperative acute ischemic stroke in acute type A aortic dissection.

OBJECTIVES: To predict preoperative acute ischemic stroke (AIS) in acute type A aortic dissection (ATAAD). METHODS: In this multi-center retrospective study, 508 consecutive patients diagnosed as ATAAD between April 2020 and March 2021 were considered for inclusion. The patients were divided into a development cohort and two validation cohorts based on time periods and centers. Clinical data and imaging findings obtained were analyzed. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with preoperative AIS. The performance of resulting nomogram was evaluated in discrimination and calibration on all cohorts. RESULTS: A total of 224 patients were in the development cohort, 94 in the temporal validation cohort, and 118 in the geographical validation cohort. Six predictors were identified: age, syncope, D-dimer, moderate to severe aortic valve insufficiency, diameter ratio of true lumen in ascending aorta < 0.33, and common carotid artery dissection. The nomogram established showed good discrimination (area under the receiver operating characteristic curve [AUC], 0.803; 95% CI: 0.742, 0.864) and calibration (Hosmer-Lemeshow test p = 0.300) in the development cohort. External validation showed good discrimination and calibration abilities in both temporal (AUC, 0.778; 95% CI: 0.671, 0.885; Hosmer-Lemeshow test p = 0.161) and geographical cohort (AUC, 0.806; 95% CI: 0.717, 0.895; Hosmer-Lemeshow test p = 0.100). CONCLUSIONS: A nomogram, based on simple imaging and clinical variables collected on admission, showed good discrimination and calibration abilities in predicting preoperative AIS for ATAAD patients. KEY POINTS: • A nomogram based on simple imaging and clinical findings may predict preoperative acute ischemic stroke in patients with acute type A aortic dissection in emergencies. • The nomogram showed good discrimination and calibration abilities in validation cohorts.

A label-free electrochemical aptasensor based on Bi-Sb alloy materials for potential POCT of HER-2.

As a prognostic biomarker for breast cancer, human epidermal growth factor receptor 2 (HER-2) is of crucial diagnostic value. Here, a label-free electrochemical aptasensor was established for the ultrasensitive detection of HER-2 using a modified electrode of Bi-Sb alloy materials (Bi-Sb AMs). The performance of the aptasensor was enhanced greatly due to the introduction of Bi-Sb alloy materials (Bi-Sb AMs) with high conductivity. Furthermore, by integrating the aptasensor with the Sensit Smart U-disk electrochemical analyzer, the point-of-care testing (POCT) for HER-2 was realized. Under the optimal experimental parameters, the POCT analyzer showed a wide linear response from 0.01 pg mL-1 to 100 ng mL-1, with a low detection limit (LOD) of 5.96 fg mL-1 for the detection of HER-2. The presented POCT analyzer exhibited good specificity, stability, and reproducibility. Benefiting from the simple operation and rapid testing, the developed analyzer will have potential application in the prognostic diagnosis and treatment of breast cancer.

The nutritional literacy of breast cancer patients receiving chemotherapy and its association with treatment self-regulation and perceived social support.

PURPOSE: Chemotherapy can lead to malnutrition and post-menopausal recurrence among breast cancer (BC) patients, who need to achieve nutritional literacy (NL) to cope. The objective of this study was to explore the NL level in Chinese BC patients receiving chemotherapy and its predictors including both internal motivation and the external environment. METHODS: A total of 326 BC female patients from three hospitals were enrolled. Participants completed the Nutrition Literacy Measurement Scale for Chinese Adult (NLMS-CA), Chinese version from the Treatment Self-Regulation Questionnaire (TSRQ-C), and the Perceived Social Support Scale (PSSS) to assess NL, treatment self-regulation, and social support. Stepwise multivariate linear regression was used to identify the main factors of NL. RESULTS: The total NL score was 151.31 ± 16.85, the "knowledge understanding" dimension had the lowest score. In the final regression model, patients with higher scores for "autonomous motivation" and "introjected regulation" on the TSRQ-C and "family support" and "other support" on the PSSS, higher educational levels and average monthly household incomes and endocrine therapy had higher NL levels (adjusted R2 = 66.7%, p < 0.05). CONCLUSIONS: The overall NL score among Chinese BC patients receiving chemotherapy was satisfactory, but the knowledge understanding score was low. Higher autonomous motivation, introjected regulation, family support and other support scores, higher educational and household income levels, and endocrine therapy were predictors of NL in female patients. Interventions should be designed according to the specific performances and predictors of NL in female patients.

Tungsten-based polyoxometalate nanoclusters with remarkable reactive oxygen species-scavenging activity efficiently quenched luminol-based electrochemiluminescence for sensitive detection of Her-2.

This study aimed to develop a quenching-type electrochemiluminescence (ECL) immunosensor for human epidermal growth factor receptor (Her-2) detection. Firstly, Pd/NiFeOx nanoflowers decorated by in situ formation of gold nanoparticles (Au NPs) and 2D Ti3C2 MXene nanosheets were synthesized (AuPd/NiFeOx/Ti3C2) as carriers to load luminol and primary antibodies. Impressively, AuPd/NiFeOx/Ti3C2 with excellent peroxidase-like activity could accelerate the decomposition of the coreactant H2O2 generating more reactive oxygen species (ROSs) under the working potential from 0 to 0.8 V, resulting in highly efficient ECL emission at 435-nm wavelengths. The introduction of tungsten-based polyoxometalate nanoclusters (W-POM NCs) which exhibit remarkable ROSs-scavenging activity as secondary antibody labels could improve the sensitivity of immunosensors. The ZnO nanoflowers were employed to encapsulate minute-sized W-POM NCs, and polydopamine was self-polymerized on the surface of Zn(W-POM)O to anchor secondary antibodies. The mechanism of the quenching strategy was explored and it was found that W-POM NCs could consume ROSs by the redox reaction of W5+ resulting in W6+. The proposed ECL immunosensor displayed a wide linear response range of 0.1 pg·mL-1 to 50 ng·mL-1, and a low detection limit of 0.036 pg mL-1 (S/N = 3). The recoveries ranged from 93.9 to 99.4%, and the relative standard deviation (RSD) was lower than 10%. This finding is promising for the design of detecting new protein biomarkers.

Deep Eutectic Solvents Based on L-Arginine and 2-Hydroxypropyl-ß-Cyclodextrin for Drug Carrier and Penetration Enhancement.

By selecting L-arginine as the hydrogen bond acceptor (HBA) and 2-hydroxypropyl-ß-cyclodextrin (2HPßCD) as the hydrogen bond donor (HBD), deep eutectic solvents (DESs) with various water content were prepared at the 4:1 mass ratio of L-arginine to 2HPßCD with 40 to 60% of water, and were studied for its application in transdermal drug delivery system (TDDS). The hydrogen bond networks and internal chemistry structures of the DESs were measured by attenuated total reflection Fourier transform infrared (ATR-FTIR) and 1H-nuclear magnetic resonance spectroscopy (1H-NMR), which demonstrated the successful synthesis of DESs. The viscosity of DES was decreased from 10,324.9 to 3219.6 mPa s, while glass transition temperature (Tg) of the DESs was increased from - 60.8 to - 51.4 °C, as the added water was increased from 45 to 60%. The solubility of ibuprofen, norfloxacin, and nateglinide in DES with 45% of water were increased by 79.3, 44.1, and 3.2 times higher than that in water, respectively. The vitro study of transdermal absorption of lidocaine in DESs showed that the cumulative amounts of lidocaine reached 252.4 µg/cm2, 226.1 µg/cm2, and 286.1 µg/cm2 at 8 h for DESs with 45%, 50%, and 60% of water, respectively. The permeation mechanism of DES with lower content of water (45%) was mainly by changing the fluidization of lipids, while changing the secondary structure of keratin in stratum corneum (SC) at higher water content (50% and 60%). These nonirritant and viscous fluid like DESs with good drug solubility and permeation enhancing effects have broad application prospect in the field of drug solubilization and transdermal drug delivery system.

Ratiometric Electrochemiluminescence Sensing of Carcinoembryonic Antigen Based on Luminol.

Ratiometric electrochemiluminescence (ECL) sensors can efficiently remove environmental interference to attain precise detection. Nonetheless, two eligible luminophores or coreactants were usually needed, increasing the complexity and restricting their practical application. In this study, a single luminophore of luminol with a single coreactant of H2O2 was employed to construct a dual-potential ratiometric ECL sensor for the detection of carcinoembryonic antigen (CEA). The produced palladium nanoclusters (Pd NCs) employing a DNA duplex as a template could not only stimulate luminol to produce cathodic ECL (Icathodic) but also quench its anodic ECL (Ianodic). During the detection process, CEA could damage the double-stranded structure and reduce the Pd NCs' amount, triggering a significant decrease in the ratio of Icathodic to Ianodic (Icathodic/Ianodic) and thereby achieving sensitive CEA's detection. Furthermore, the Icathodic/Ianodic was independent of the H2O2 concentration, which avoided a prejudicial effect from H2O2 decomposition and considerably enhanced the detection's reliability. The developed ratiometric ECL sensor demonstrated a sensitive detection toward CEA with a wide linear range from 100 ag/mL to 10 ng/mL and a detection limit of 87.1 ag/mL (S/N = 3). In conclusion, this study offers a new idea for constructing ratiometric ECL sensors based on a single luminophore and technical support for cancer's early diagnosis.

Serum neurofilament light reflects cognitive dysfunctions in children with obstructive sleep apnea.

BACKGROUND: In children, obstructive sleep apnea (OSA) can cause cognitive dysfunctions. Amyloid-beta and tau are elevated in OSA. Neurofilament light (NfL) is a marker of neuro-axonal damage, but there are no reports of NfL for OSA. The objective was to investigate the serum levels of NfL and tau in children with or without OSA and explore their relationship with cognitive dysfunctions caused by OSA. METHODS: This retrospective case-control study included children diagnosed with adenoid tonsil hypertrophy from July 2017 to September 2019 at the Second Affiliated Hospital of Xi'an Jiaotong University. Correlations between cognitive scores and tau and NfL were examined. RESULTS: Fifty-six OSA and 49 non-OSA children were included. The serum NfL levels were higher in the OSA group (31.68 (27.29-36.07) pg/ml) than in the non-OSA group (19.13 (17.32-20.95) pg/ml) (P < 0.001). Moreover, NfL was correlated with the course of the disease, apnea-hypopnea index (AHI), obstructive apnea index (OAI), obstructive apnea-hypopnea index (OAHI), average oxygen saturation (SaO2), respiratory arousal index (RAI), and cognitive dysfunctions evaluated by the Chinese Wechsler Intelligence Scale for Children (C-WISC) (all P < 0.05). The area under the receiver operating characteristics curve (AUC) of NfL was 0.816 (95%CI: 0.736-0.897). Multiple regression analysis revealed that NfL was significantly associated with verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ) and full-scale intelligence quotient (FIQ) (P < 0.001, respectively). CONCLUSIONS: Serum NfL levels are associated with the severity of cognitive dysfunctions in children diagnosed with adenoid tonsil hypertrophy and might be a candidate noninvasive, objective marker to identify cognitive dysfunctions in children with OSA.