Dual chemical bonding construction of electrochemical peptide sensor based on GDY/MOFs(Fe) composite for ultra-low determination of prostate-specific antigen.

A novel "double chemical bonding" electrochemical peptide biosensor 2FcP-GA-GDY(Fe)@NMIL-B was developed for highly selective, ultrasensitive, and ultrastable identification of prostate-specific antigen (PSA). The C-Fe-O chemical bond linking Fe-Graphdiyne (Fe-GDY) with NH2-MIL88B(Fe) (NMIL88B) as the first chemical bonding of electrode carrier Fe-GDY@NH2-MIL88B(Fe) (GDY(Fe)@NMIL) significantly accelerates electron transport. With glutaraldehyde (GA) as a crosslinking agent, the Schiff-base -NC- formed by GDY(Fe)@NMIL nanocomposites links the two Fc molecules labeled peptides (2FcP) as the second chemical bonding, facilitating high-density attachment of peptides to the electrode carrier in a firm manner. When the PSA analyte is introduced to identify and cleave the specific peptide, the release of ferrocene from its head leads to a decrease in the electrical signal, enabling sensitive detection. The prepared sensing platform exhibits exceptional analytical performance for PSA with an extended linear response range from 10 fg mL-1 to 50 ng mL-1. Additionally, the detection limit has been significantly reduced to an ultra-low level of only 0.94 fg mL-1, surpassing those reported in most literature by several orders of magnitude. Moreover, the 2FcP-GA-GDY(Fe)@NMIL-B sensor has excellent selectivity and stability while also showcasing great potential for practical application of PSA detection in human serum using the standard addition method.

Diagnostic and predictive significance of the ferroptosis-related gene TXNIP in lung adenocarcinoma stem cells based on multi-omics.

BACKGROUND: Lung cancer stands as the foremost cause of cancer-related fatalities globally. The presence of cancer stem cells (CSCs) poses a challenge, rendering current targeted tumor therapies ineffective. This study endeavors to investigate a novel therapeutic approach focusing on ferroptosis and delves into the expression of ferroptosis-related genes within lung CSCs. METHODS: We systematically examined RNA-seq datasets derived from lung tumor cells (LTCs) and lung cancer stem cells (LSCs), as previously investigated in our research. Our focus was on analyzing differentially expressed genes (DEGs) related to ferroptosis. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), we conducted functional analysis of these ferroptosis-related DEGs. Additionally, we employed protein‒protein interaction networks to identify hub genes. LC‒MS/MS analysis of LTCs and LSCs was conducted to pinpoint the crucial ferroptosis-related gene-thioredoxin-interacting protein (TXNIP).Further, we delved into the immune cell infiltration landscape of LTCs and LSCs, examining the correlation between TXNIP and lung adenocarcinoma (LUAD) using data from The Cancer Genome Atlas (TCGA) database. To complement these findings, we measured the expression levels of TXNIP, glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4 (NCOA4) in LUAD tissues through immunohistochemistry (IHC) staining. RESULTS: A total of 651 DEGs were identified, with 17 of them being ferroptosis-related DEGs. These seventeen genes were categorized into four groups: driver genes, suppressor genes, unclassified genes, and inducer genes. Enrichment analysis revealed significant associations with oxidative stress, cell differentiation, tissue development, and cell death processes. The RNA-seq analysis demonstrated consistent gene expression patterns with protein expression, as evidenced by mass spectrometry analysis. Among the identified genes, SFN and TXNIP were singled out as hub genes, with TXNIP showing particularly noteworthy expression. The expression of the ferroptosis-related gene TXNIP exhibited correlations with the presence of an immunosuppressive microenvironment, TNM stages, and the degree of histological differentiation.Also, the ferroptosis-markers GPX4 and NCOA4 displayed correlations with LUAD. This comprehensive analysis underscores the significance of TXNIP in the context of ferroptosis-related processes and their potential implications in cancer development and progression. CONCLUSION: The investigation conducted in this study systematically delved into the role of the ferroptosis-related gene TXNIP in Lung CSCs. The identification of TXNIP as a potentially valuable biomarker in this context could have significant implications for refining prognostic assessments and optimizing therapeutic strategies for advanced lung cancer.

A novel dilated contextual attention module for breast cancer mitosis cell detection.

Background and object: Mitotic count (MC) is a critical histological parameter for accurately assessing the degree of invasiveness in breast cancer, holding significant clinical value for cancer treatment and prognosis. However, accurately identifying mitotic cells poses a challenge due to their morphological and size diversity. Objective: We propose a novel end-to-end deep-learning method for identifying mitotic cells in breast cancer pathological images, with the aim of enhancing the performance of recognizing mitotic cells. Methods: We introduced the Dilated Cascading Network (DilCasNet) composed of detection and classification stages. To enhance the model's ability to capture distant feature dependencies in mitotic cells, we devised a novel Dilated Contextual Attention Module (DiCoA) that utilizes sparse global attention during the detection. For reclassifying mitotic cell areas localized in the detection stage, we integrate the EfficientNet-B7 and VGG16 pre-trained models (InPreMo) in the classification step. Results: Based on the canine mammary carcinoma (CMC) mitosis dataset, DilCasNet demonstrates superior overall performance compared to the benchmark model. The specific metrics of the model's performance are as follows: F1 score of 82.9%, Precision of 82.6%, and Recall of 83.2%. With the incorporation of the DiCoA attention module, the model exhibited an improvement of over 3.5% in the F1 during the detection stage. Conclusion: The DilCasNet achieved a favorable detection performance of mitotic cells in breast cancer and provides a solution for detecting mitotic cells in pathological images of other cancers.

Neutralizing monoclonal antibodies protect against human adenovirus type 55 infection in transgenic mice and tree shrews.

Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques (Macaca mulatta) that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.

Inter-patient ECG heartbeat classification for arrhythmia classification: a new approach of multi-layer perceptron with weight capsule and sequence-to-sequence combination.

Objective: The objective of this research is to construct a method to alleviate the problem of sample imbalance in classification, especially for arrhythmia classification. This approach can improve the performance of the model without using data enhancement. Methods: In this study, we have developed a new Multi-layer Perceptron (MLP) block and have used a Weight Capsule (WCapsule) network with MLP combined with sequence-to-sequence (Seq2Seq) network to classify arrhythmias. Our work is based on the MIT-BIH arrhythmia database, the original electrocardiogram (ECG) data is classified according to the criteria recommended by the American Association for Medical Instrumentation (AAMI). Also, our method's performance is further evaluated. Results: The proposed model is evaluated using the inter-patient paradigm. Our proposed method shows an accuracy (ACC) of 99.88% under sample imbalance. For Class N, sensitivity (SEN) is 99.79%, positive predictive value (PPV) is 99.90%, and specificity (SPEC) is 99.19%. For Class S, SEN is 97.66%, PPV is 96.14%, and SPEC is 99.85%. For Class V, SEN is 99.97%, PPV is 99.07%, and SPEC is 99.94%. For Class F, SEN is 97.94%, PPV is 98.70%, and SPEC is 99.99%. When using only half of the training sample, our method shows that the SEN of Class N and V is 0.97% and 5.27% higher than the traditional machine learning algorithm. Conclusion: The proposed method combines MLP, weight capsule network with Seq2seq network, effectively addresses the problem of sample imbalance in arrhythmia classification, and produces good performance. Our method also shows promising potential in less samples.

The Epidemiology of Tinea Capitis in Guangxi Province, China.

The aim of this study was to analyze the epidemiological characteristics and pathogen spectrum of tinea capitis in Guangxi, southern China. A multicenter prospective descriptive study was conducted in 8 hospitals across Guangxi. From January 2019 to July 2022, one hundred seventy-one (171) patients diagnosed with tinea capitis were included. Demographic data, risk factors, and fungal data were collected. If necessary, species were further identified by morphological or molecular sequencing in the central laboratory. Of the 171 cases of tinea capitis, 74.3% occurred in patients aged 2-8 years. Children with tinea capitis were mainly boys (59.6%) and were more likely than adults to have a history of animal contact (44.2% vs. 33.3%) and zoophilic dermatophyte infection (76.9% vs. 46.7%, P = 0.008). The adults were mainly female (53%) and were more likely than children to have a history of infection with anthropophilic organisms (53.3% vs. 18.9%). The causative agents of tinea capitis in Guangxi were diverse, and the most common pathogen was Microsporum canis (M. cani, n = 98, 62%), followed by Trichophyton mentagrophytes (T. mentagrophytes n = 18, 11.4%) and Trichophyton tonsurans (T. tonsurans n = 12, 7.6%). In addition, tinea capitis caused by Nannizzia incurvata (N. incurvata) and Trichophyton verrucosum (T. verrucosum) was detected in the study. Notably, the proportion of patients with kerion in the study was 41.5% (n = 71), and most of those patients were children (n = 68), especially neglected children living in the rural mountainous areas of Guangxi, where they were unable to receive timely diagnosis and appropriate treatment. In conclusion, the causative agents of tinea capitis in Guangxi, South China, are diverse, and the incidence of kerion is high, indicating that diagnosis and treatment modalities in the region remain grossly inadequate. Clinicians and policy-makers should collaborate to adopt public health strategies to control the disease.

Influencing factors of health resource allocation and utilisation before and after COVID-19 based on RIF-I-OLS decomposition method: a longitudinal retrospective study in Guangdong Province, China.

OBJECTIVES: To explore factors that influenced the health resource allocation and utilisation before and after COVID-19, and subsequently offer sensible recommendations for advancing the scientific distribution of health resources. DESIGN: A longitudinal survey using 2017-2020 data, which were collected for analysis. SETTING: The study was conducted based on data collected from the Health Commission of Guangdong Province's website. OUTCOME MEASURES: Eight health resource indicators and four health resource utilisation indicators were included in the factor analysis. Four indices were calculated to measure the inequality in health resource allocation and utilisation. We analysed factors for the inequality indices using the recentred influence function index ordinary least squares decomposition method. RESULTS: The health resource inequality indices peaked in 2020 (Gini coefficient (Gini): 0.578, Absolute Gini coefficient (AGini): 1.136, Concentration Index (CI): 0.417, Absolute CI (ACI): 0.821), whereas the health resource utilisation inequality indices declined year by year, thus reaching their lowest point in that same year. The majority of inequality indices in the annual change of health resource allocation were at their lowest in 2020 (Gini: -1.672, AGini: 0.046, CI: -0.189, ACI: 0.005), while the use of health resources declined dramatically, showing a negative growth trend. The inequality indices of health resource allocation and utilisation in 2020 were affected by a number of variables, including the COVID-19 level, (p<0.05), while the proportion of expenditure on public health was the most significant one. CONCLUSIONS: Guangdong Province's health resource allocation and utilisation were still concentrated in economically developed regions from 2017 to 2020. The health resource allocation inequality indices increased, especially under COVID-19, but the health resource utilisation inequality indices decreased. Measures should be taken to adjust the health resource allocation scientifically, which will fulfil the changing needs and the use of resources more efficiently. One effective measure is reasonably increasing the proportion of expenditure on public health.

Antifungal alkaloids from the branch-leaves of Clausena lansium Lour. Skeels (Rutaceae).

BACKGROUND: The rational utilization of botanical secondary metabolites is one of the strategies to reduce the application of chemical fungicides. The extensive biological activities of Clausena lansium indicate that it has the potential to develop botanical fungicides. RESULTS: A systematic investigation on the antifungal alkaloids from C. lansium branch-leaves following bioassay-guided isolation was implemented. Sixteen alkaloids, including two new and nine known carbazole alkaloids, one known quinoline alkaloid and four known amides, were isolated. Compounds 4, 7, 12 and 14 showed strong antifungal activity on Phytophthora capsiciwith EC50 values ranging from 50.67 to 70.82 µg mL-1 . Compounds 1, 3, 8, 10, 11, 12 and 16 displayed different degrees of antifungal activity against Botryosphaeria dothidea with EC50 values ranging from 54.18 to 129.83 µg mL-1 . It was reported for the first time that these alkaloids had antifungal effects on P. capsici or B. dothidea, and their structure-activity relationships were further discussed systematically. Additionally, among all alkaloids, dictamine (12) had the strongest antifungal activities against P. capsici (EC50  = 50.67 µg mL-1 ) and B. dothidea (EC50  = 54.18 µg mL-1 ), and its physiological effects on P. capsici and B. dothidea also were further evaluated. CONCLUSION: Capsicum lansium is a potential source of antifungal alkaloids, and C. lansium alkaloids had the potential as lead compounds of botanical fungicides in the development of new fungicides with novel action mechanism. © 2023 Society of Chemical Industry.

MXene-MoS2 heterostructure collaborated with catalyzed hairpin assembly for label-free electrochemical detection of microRNA-21.

Abnormal expression of microRNAs is greatly associated with the occurrence of various cancer types, revealing great potential of microRNA as biomarkers for cancer diagnosis and prognosis. Herein, a MXene-MoS2 heterostructure enhancing electrochemical biosensor coupled with catalytic hairpin assembly (CHA) amplification approach for label-free determination of microRNA-21 (miR-21) was successfully assembled. In particular, the unique micro-nano heterostructure with large specific area and favorable electroconductivity exhibited the ability of excellent confinement effect. Thus, rendered the MXene-MoS2 heterostructure the ability to trigger more target recycling reaction, giving new vitality to the traditional CHA amplification method. Meanwhile, thionine (Thi) and gold nanoparticles (AuNPs) were anchoring at the surface of MXene-MoS2 heterostructure, respectively, empowered the sensor the capability of capture probes fixation and miR-21 label-free determination. When numerous electronegative double-stranded DNA generated, the electron transfer was greatly hindered, resulting in signal decrease. Accordingly, the design denoted a broad dynamic range from 100 fM to 100 nM and a detection limit of about 26 fM, comparable or lower than previous reported methods for miR-21 detection. Furthermore, the sensing platform supplied satisfactory selectivity, reproducibility and stability towards the miR-21 detection. The real sample determination also showed a promising performance under clinical circumstance. Finally, from the clinical standpoint, the proposed biosensor is a considerable platform toward early disease detection and monitoring.

Reliability and validity of the Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) in Chinese people.

OBJECTIVE: To investigate the reliability and validity of Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) for different population cohorts in the city of Guangzhou, Guangdong, China and to provide evidence and tools for further evaluation of healthy fitness of Chinese population and related factors. DESIGN: Cross-sectional study. SETTING: Urban neighbourhood and Medical University. PARTICIPANTS: Elderly people (n=393; mean age 68.27±6.38 years; 53.18% male), university students (n=390; mean age 19.29±1.29 years; 38.21% male) and urban residents (n=393; mean age 32.23±9.41 years; 44.78% male). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were evaluated the reliability and validity of HFMS V1.0 by internal consistency evaluation, split-half reliability, test-retest reliability, convergent and discriminant construct validity, and factor analysis. RESULTS: The Cronbach's α coefficients for HFMS V1.0 were all greater than 0.85 for overall scale of total samples and three individual groups, and the split-half reliability and intragroup correlation coefficients were both greater than 0.70 (p<0.01). The correlation of each item, dimension and subscales ranged from 0.52 to 0.91 (p < 0.01). A total of 10 factors were screened by exploratory factor analysis with the cumulative contribution rate of 61.40%, basically consistent with the theoretical structure of scale. The confirmatory factor analysis indicated good fit: CMIN/DF=3.45, root mean square error of approximation=0.05, GFI=0.91, AGFI=0.90, IFI=0.90, comparative fit index=0.90. CONCLUSION: HFMS V1.0 showed acceptable reliability and validity in the test of healthy fitness of general population in Guangzhou. This scale could be a reliable measurement tool for evaluation of healthy fitness and potential risk factors.

Reliability and validity of Healthy Fitness Measurement Scale Version1.0 (HFMS V1.0) in Chinese elderly people.

PURPOSE: We examined the reliability and validity of the Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) specifically on elderly people in China. METHODS: We carried out a cross-sectional study in December 2020 and enrolled 800 elderly people through stratified sampling technique, including 777 valid samples (with a mean age of 71.81 ± 8.36 years), of which 382 cases (49.2%) were women. The level of healthy fitness was measured using the HFMS V1.0. The Cronbach's alpha coefficient, split-half reliability, test-retest reliability, convergent and discriminant validity, exploratory factor and confirmatory factor were calculated for assessing the reliability and validity of HFMS V1.0. RESULTS: HFMS V1.0 consists of 8 dimensions and 38 items. The scale had acceptable reliability (Cronbach's alpha = 0.920, split-half = 0.946, test-retest = 0.878). Exploratory factor analysis showed KMO value =0.927, and uncovered 10 factors with the cumulative contribution rate of 65.71% and all factor loads over 0.40. The item distribution was consistent with the initial expectation of the scale. The confirmatory factor analysis indicated good fit: CMIN/DF = 2.796, RMSEA = 0.048, IFI =0.914, TLI = 0.902, CFI = 0.913. CONCLUSION: HFMS V1.0 was shown to have acceptable reliability and validity indices for this sample. Collectively, HFMS V1.0 is reliable and efficient to measure the healthy fitness of elderly people. It is recommended to use it among the elderly in other Chinese cities in the future to ensure uniformity and objectivity. This scale can be carried out to evaluate of the effectiveness of public health measures in improving the healthy fitness level of the elderly and optimizing public health policies.

Flexible nickel-cobalt double hydroxides micro-nano arrays for cellular secreted hydrogen peroxide in-situ electrochemical detection.

It is critical to detect cellular secreted hydrogen peroxide (H2O2) in situ for clinical diagnosis, biomedical research and cancer treatment. Herein, the electrochemical determination of H2O2 released by cancer cells grown on the surface of carbon cloth supported NiCo-DH/AuPt micro-nano arrays to elevate the capability of in situ signal collection was achieved. NiCo-DH/AuPt @CC was successfully prepared using the cobalt based metal-organic framework (Co-MOF) as a presoma after in situ etching growth onto the CC and electrodeposition of gold and platinum nanoparticles (AuPt NPs). Under the optimal conditions, owing to the excellent catalytic efficiency of NiCo-DH and AuPt NPs, the designed sensor performs a relatively wider linear range to H2O2 concentration from 10 µM to 22.08 mM, and the limit of detection is 0.145 µM. Accordingly, the as-prepared sensing system was also applied to determine H2O2 secreted by living cells which grown on the surface of NiCo-DH/AuPt @CC with satisfactory consequences. In possession of the superior sensitivity, selectivity, reproducibility, the NiCo-DH/AuPt @CC is a luciferous platform for the real time detection of H2O2 in the area of biomedical and clinical diagnosis.

A disposable and sensitive non-enzymatic glucose sensor based on 3D graphene/Cu2O modified carbon paper electrode.

Herein, a three-dimensional graphene wall (GWs) and nano-Cu2O modified carbon fiber paper (CFP) electrode were used to develop a disposable and sensitive non-enzymatic glucose sensor. This sensing interface of GWs/Cu2O consists of an interlaced CFP on which intercrossed graphene walls (GWs) were vertically tethered in situ by radio frequency plasma enhanced chemical vapor deposition (RF-PECVD), and Cu2O nanoparticles (NPs) were evenly grew on the 3D GWs layer and skeleton through the complete thermal decomposition of copper acetate (Cu (CH3COO)2) at high temperature. The CFP/GWs/Cu2O shows a large specific surface area and rich solution diffusion channels, which can expose more catalytic active sites without Nafion fixation film, thus greatly improving the electrocatalytic performance of this glucose sensor. The CFP/GWs/Cu2O sensor shows excellent catalytic performance to glucose with a linear detection range of 0.5 µM-5166 µM, LOD of 0.21 µM, and response time <4 s. This kind of disposable and sensitive electrode can capable of controlling uniform growth and accurate quantification, and has great development potential in the field of medical detection and the commercialization of wearable sensors.

Sensitivity analysis of three-parallel-DAEM-reaction model for describing rice straw pyrolysis.

The three-parallel-DAEM-reaction model was used to study the slow pyrolysis kinetics of rice straw based on thermogravimetric analysis (TGA) data. The kinetic parameters of the model were calculated using the pattern search method. A comparison between the predicted DTG data and experimental values showed good agreement. The influences of the kinetic parameters on the model for describing the experimental data of rice straw were analyzed by means of local parametric sensitivity analysis. The results indicated that the frequency factor and the mean value of the activation distribution for cellulose decomposition affect the model more strongly than other parameters, followed by the corresponding parameters for hemicellulose and lignin. The sensitivity of the model to the standard deviations of the activation energy distributions for all pseudocomponents is very slight.