Exploring optimal pathways for enterprise procurement management systems based on fast neural modeling and semantic segmentation.

Corporate procurement management assumes a pivotal role within the contemporary business landscape, yet confronts an array of challenges as markets continue to evolve and globalize. Conventional procurement management systems frequently grapple with issues of inefficiency, resource depletion, and noncompliance, necessitating the exploration of innovative avenues for optimization. This paper delves into the realm of risk mitigation associated with collusion behavior in the administration of intelligent procurement systems, presenting a novel procurement collusion identification model founded on a convolutional neural network (CNN) with reinforcement learning techniques. This framework commences with the application of a CNN and Long Short-Term Memory (LSTM) network for in-depth feature analysis and initial identification of historical procurement data, subsequently leveraging reinforcement learning methodologies to enhance the model's autonomy and intelligence for the purpose of optimization. Throughout the experimental phase, diverse domains of procurement data were meticulously selected for analysis. The empirical findings unequivocally demonstrate the model's proficiency, with an average recognition accuracy of 95.1% across five publicly available datasets. This performance surpasses existing machine learning methodologies employed in contemporary research and common recognition networks, thereby offering a pioneering reference point for the intelligent administration and optimization of future procurement systems.

Deep learning with diffusion MRI as in vivo microscope reveals sex-related differences in human white matter microstructure.

Biological sex is a crucial variable in neuroscience studies where sex differences have been documented across cognitive functions and neuropsychiatric disorders. While gross statistical differences have been previously documented in macroscopic brain structure such as cortical thickness or region size, less is understood about sex-related cellular-level microstructural differences which could provide insight into brain health and disease. Studying these microstructural differences between men and women paves the way for understanding brain disorders and diseases that manifest differently in different sexes. Diffusion MRI is an important in vivo, non-invasive methodology that provides a window into brain tissue microstructure. Our study develops multiple end-to-end classification models that accurately estimates the sex of a subject using volumetric diffusion MRI data and uses these models to identify white matter regions that differ the most between men and women. 471 male and 560 female healthy subjects (age range, 22-37 years) from the Human Connectome Project are included. Fractional anisotropy, mean diffusivity and mean kurtosis are used to capture brain tissue microstructure characteristics. Diffusion parametric maps are registered to a standard template to reduce bias that can arise from macroscopic anatomical differences like brain size and contour. This study employ three major model architectures: 2D convolutional neural networks, 3D convolutional neural networks and Vision Transformer (with self-supervised pretraining). Our results show that all 3 models achieve high sex classification performance (test AUC 0.92-0.98) across all diffusion metrics indicating definitive differences in white matter tissue microstructure between males and females. We further use complementary model architectures to inform about the pattern of detected microstructural differences and the influence of short-range versus long-range interactions. Occlusion analysis together with Wilcoxon signed-rank test is used to determine which white matter regions contribute most to sex classification. The results indicate that sex-related differences manifest in both local features as well as global features / longer-distance interactions of tissue microstructure. Our highly consistent findings across models provides new insight supporting differences between male and female brain cellular-level tissue organization particularly in the central white matter.

Construction of a streptavidin-based dual-localized DNAzyme walker for disease biomarker detection.

A dual-localized DNAzyme walker (dlDW) was constructed by utilizing multiple split DNAzymes with probes, and their substrates are separately localized on streptavidin and AuNPs, serving as walking pedals and tracks, respectively. Based on dlDW, biosensing platform was successfully constructed and showed great potential application in clinical disease diagnosis.

Subject-Agnostic Transformer-Based Neural Speech Decoding from Surface and Depth Electrode Signals.

Objective: This study investigates speech decoding from neural signals captured by intracranial electrodes. Most prior works can only work with electrodes on a 2D grid (i.e., Electrocorticographic or ECoG array) and data from a single patient. We aim to design a deep-learning model architecture that can accommodate both surface (ECoG) and depth (stereotactic EEG or sEEG) electrodes. The architecture should allow training on data from multiple participants with large variability in electrode placements and the trained model should perform well on participants unseen during training. Approach: We propose a novel transformer-based model architecture named SwinTW that can work with arbitrarily positioned electrodes, by leveraging their 3D locations on the cortex rather than their positions on a 2D grid. We train both subject-specific models using data from a single participant as well as multi-patient models exploiting data from multiple participants. Main Results: The subject-specific models using only low-density 8x8 ECoG data achieved high decoding Pearson Correlation Coefficient with ground truth spectrogram (PCC=0.817), over N=43 participants, outperforming our prior convolutional ResNet model and the 3D Swin transformer model. Incorporating additional strip, depth, and grid electrodes available in each participant (N=39) led to further improvement (PCC=0.838). For participants with only sEEG electrodes (N=9), subject-specific models still enjoy comparable performance with an average PCC=0.798. The multi-subject models achieved high performance on unseen participants, with an average PCC=0.765 in leave-one-out cross-validation. Significance: The proposed SwinTW decoder enables future speech neuroprostheses to utilize any electrode placement that is clinically optimal or feasible for a particular participant, including using only depth electrodes, which are more routinely implanted in chronic neurosurgical procedures. Importantly, the generalizability of the multi-patient models suggests the exciting possibility of developing speech neuroprostheses for people with speech disability without relying on their own neural data for training, which is not always feasible.

Heteromultivalent DNA Enhances the Assembly Yield of Hybrid Nanoparticles and Facilitates Dynamic Disassembly for Bioanalysis Using ICP-MS.

To obtain enhanced physical and biological properties, various nanoparticles are typically assembled into hybrid nanoparticles through the binding of multiple homologous DNA strands to their complementary counterparts, commonly referred to as homomultivalent assembly. However, the poor binding affinity and limited controllability of homomultivalent disassembly restrict the assembly yield and dynamic functionality of the hybrid nanoparticles. To achieve a higher binding affinity and flexible assembly choice, we utilized the paired heteromultivalency DNA to construct hybrid nanoparticles and demonstrate their excellent assembly characteristics and dynamic applications. Specifically, through heteromultivalency, DNA-functionalized magnetic beads (MBs) and gold nanoparticles (AuNPs) were efficiently assembled. By utilizing ICP-MS, the assembly efficiency of AuNPs on MBs was directly monitored, enabling quantitative analysis and optimization of heteromultivalent binding events. As a result, the enhanced assembly yield is primarily attributed to the fact that heteromultivalency allows for the maximization of effective DNA probes on the surface of nanoparticles, eliminating steric hindrance interference. Subsequently, with external oligonucleotides as triggers, it was revealed that the disassembly mechanism of hybrid nanoparticles was initiated, which was based on an increased local concentration rather than toehold-mediated displacement of paired heteromultivalency DNA probes. Capitalizing on these features, an output platform was then established based on ICP-MS signals that several Boolean operations and analytical applications can be achieved by simply modifying the design sequences. The findings provide new insights into DNA biointerface interaction, with potential applications to complex logic operations and the construction of large DNA nanostructures.

Imaging classification of prostate cancer with extracapsular extension and its impact on positive surgical margins after laparoscopic radical prostatectomy.

Abstract: To explore the impact of different imaging classifications of prostate cancer (PCa) with extracapsular extension (EPE) on positive surgical margins (PSM) after laparoscopic radical prostatectomy. Methods: Clinical data were collected for 114 patients with stage PT3a PCa admitted to Ningbo Yinzhou No. 2 Hospital from September 2019 to August 2023. Radiologists classified the EPE imaging of PCa into Type I, Type II, and Type III. A chi-square test or t-test was employed to analyze the factors related to PSM. Multivariate regression analysis was conducted to determine the factors associated with PSM. Receiver operating characteristic curve analysis was used to calculate the area under the curve and evaluate the diagnostic performance of our model. Clinical decision curve analysis was performed to assess the clinical net benefit of EPE imaging classification, biopsy grade group (GG), and combined model. Results: Among the 114 patients, 58 had PSM, and 56 had negative surgical margins. Multivariate analysis showed that EPE imaging classification and biopsy GG were risk factors for PSM after laparoscopic radical prostatectomy. The areas under the curve for EPE imaging classification and biopsy GG were 0.677 and 0.712, respectively. The difference in predicting PSM between EPE imaging classification and biopsy GG was not statistically significant (P>0.05). However, when used in combination, the diagnostic efficiency significantly improved, with an increase in the area under the curve to 0.795 (P<0.05). The clinical decision curve analysis revealed that the clinical net benefit of the combined model was significantly higher than that of EPE imaging classification and biopsy GG. Conclusions: EPE imaging classification and biopsy GG were associated with PSM after laparoscopic radical prostatectomy, and their combination can significantly improve the accuracy of predicting PSM.

Blood biomarkers for post-stroke cognitive impairment: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Post-stroke cognitive impairment (PSCI) is a frequent consequence of stroke, which affects the quality of life and prognosis of stroke survivors. Numerous studies have indicated that blood biomarkers may be the key determinants for predicting and diagnosing cognitive impairment, but the results remain varied. Therefore, this meta-analysis aims to summarize potential biomarkers associated with PSCI. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched for studies exploring blood biomarkers associated with PSCI from inception to 15 April 2022. RESULTS: 63 studies were selected from 4,047 references, which involves 95 blood biomarkers associated with the PSCI. We meta-analyzed 20 potential blood biomarker candidates, the results shown that the homocysteine (Hcy) (SMD=0.35; 95%CI: 0.20-0.49; P<0.00001), c-reactive protein (CRP) (SMD=0.49; 95%CI: 0.20-0.78; P=0.0008), uric acid (UA) (SMD=0.41; 95%CI: 0.06-0.76; P=0.02), interleukin 6 (IL-6) (SMD=0.92; 95% CI: 0.27-1.57; P=0.005), cystatin C (Cys-C) (SMD=0.58; 95%CI: 0.28-0.87; P=0.0001), creatinine (SMD=0.39; 95%CI: 0.23-0.55; P<0.00001) and tumor necrosis factor alpha (TNF-α) (SMD=0.45; 95%CI: 0.08-0.82; P=0.02) levels were significantly higher in patients with PSCI than in the non-PSCI group. CONCLUSION: Based on our findings, we recommend that paramedics focus on the blood biomarkers levels of Hcy, CRP, UA, IL-6, Cys-C, creatinine and TNF-α in conjunction with neuroimaging and neuropsychological assessment to assess the risk of PSCI, which may help with early detection and timely preventive measures. At the same time, other potential blood biomarkers should be further validated in future studies.

SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis.

BACKGROUND: Angiogenesis, which plays a critical role in embryonic development and tissue repair, is controlled by a set of angiogenic signaling pathways. As a TF (transcription factor) belonging to the basic helix-loop-helix family, HEY (hairy/enhancer of split related with YRPW motif)-1 (YRPW motif, abbreviation of 4 highly conserved amino acids in the motif) has been identified as a key player in developmental angiogenesis. However, the precise mechanisms underlying HEY1's actions in angiogenesis remain largely unknown. Our previous studies have suggested a potential role for posttranslational SUMOylation in the dynamic regulation of vascular development and organization. METHODS: Immunoprecipitation, mass spectrometry, and bioinformatics analysis were used to determine the biochemical characteristics of HEY1 SUMOylation. The promoter-binding capability of HEY1 was determined by chromatin immunoprecipitation, dual luciferase, and electrophoretic mobility shift assays. The dimerization pattern of HEY1 was determined by coimmunoprecipitation. The angiogenic capabilities of endothelial cells were assessed by CCK-8 (cell counting kit-8), 5-ethynyl-2-deoxyuridine staining, wound healing, transwell, and sprouting assays. Embryonic and postnatal vascular growth in mouse tissues, matrigel plug assay, cutaneous wound healing model, oxygen-induced retinopathy model, and tumor angiogenesis model were used to investigate the angiogenesis in vivo. RESULTS: We identified intrinsic endothelial HEY1 SUMOylation at conserved lysines by TRIM28 (tripartite motif containing 28) as the unique E3 ligase. Functionally, SUMOylation facilitated HEY1-mediated suppression of angiogenic RTK (receptor tyrosine kinase) signaling and angiogenesis in primary human endothelial cells and mice with endothelial cell-specific expression of wild-type HEY1 or a SUMOylation-deficient HEY1 mutant. Mechanistically, SUMOylation facilitates HEY1 homodimer formation, which in turn preserves HEY1's DNA-binding capability via recognition of E-box promoter elements. Therefore, SUMOylation maintains HEY1's function as a repressive TF controlling numerous angiogenic genes, including RTKs and Notch pathway components. Proangiogenic stimuli induce HEY1 deSUMOylation, leading to heterodimerization of HEY1 with HES (hairy and enhancer of split)-1, which results in ineffective DNA binding and loss of HEY1's angiogenesis-suppressive activity. CONCLUSIONS: Our findings demonstrate that reversible HEY1 SUMOylation is a molecular mechanism that coordinates endothelial angiogenic signaling and angiogenesis, both in physiological and pathological milieus, by fine-tuning the transcriptional activity of HEY1. Specifically, SUMOylation facilitates the formation of the HEY1 transcriptional complex and enhances its DNA-binding capability in endothelial cells.

Monolayer Borophene Formation on Cu(111) Surface Triggered by ⟨ 1 1 ¯ 0 ⟩ $\langle {1\bar{1}0} \rangle $ Step Edge.

Borophene, a promising material with potential applications in electronics, energy storage, and sensors, is successfully grown as a monolayer on Ag(111), Cu(111), and Au(111) surfaces using molecular beam epitaxy. The growth of two-dimensional borophene on Ag(111) and Au(111) is proposed to occur via surface adsorption and boron segregation, respectively. However, the growth mode of borophene on Cu(111) remains unclear. To elucidate this, scanning tunneling microscopy in conjunction with theoretical calculations is used to study the phase transformation of boron nanostructures under post-annealing treatments. Results show that by elevating the substrate temperature, boron nanostructures undergo an evolution from amorphous boron to striped-phase borophene (η = 1/6) adhering to the Cu ⟨ 1 1 ¯ 0 ⟩ $\langle {1\bar{1}0} \rangle $ step edge, and finally to irregularly shaped ß-type borophene (η = 5/36) either on the substrate surface or embedded in the topmost Cu layer. dI/dV spectra recorded near the borophene/Cu lateral interfaces indicate that the striped-phase borophene is a metastable phase, requiring more buckling and electron transfer to stabilize the crystal structure. These findings offer not only an in-depth comprehension of the ß-type borophene formation on Cu(111), but also hold potential for enabling borophene synthesis on weakly-binding semiconducting or insulating substrates with 1D active defects.

Surface gap solitons in the Schrödinger equation with quintic nonlinearity and a lattice potential.

We demonstrate the existence of surface gap solitons, a special type of asymmetric solitons, in the one-dimensional nonlinear Schrödinger equation with quintic nonlinearity and a periodic linear potential. The nonlinearity is suddenly switched in a step-like fashion in the middle of the transverse spatial region, while the periodic linear potential is chosen in the form of a simple sin 2 lattice. The asymmetric nonlinearities in this work can be realized by the Feshbach resonance in Bose-Einstein condensates or by the photorefractive effect in optics. The major peaks in the gap soliton families are asymmetric and they are located at the position of the jump in nonlinearity (at x = 0). In addition, the major peaks of the two-peak and multi-peak solitons at the position x = 0 are higher than those after that position, at x > 0. And such phenomena are more obvious when the value of chemical potential is large, or when the difference of nonlinearity values across the jump is big. Along the way, linear stability analysis of the surface gap solitons is performed and the stability domains are identified. It is found that in this model, the solitons in the first band gap are mostly stable (excepting narrow domains of instability at the edges of the gap), while those in the second band gap are mostly unstable (excepting extremely narrow domains of stability for fundamental solitons). These findings are also corroborated by direct numerical simulations.

Advances of liquid metal hydrogel composites in biomedical applications.

Liquid metals (LMs) and hydrogels each represent advanced frontiers in emerging biomaterials and biomedicine. In particular, LMs, which possess liquid and metallic properties at normal temperature and pressure, are a new type of conductive material that has gained increasing attention. When integrated into hydrogel polymers, LMs act exceptionally as an "active" filler and/or responsive element. The presence of LMs in these composites endows the liquid metal hydrogel composites (LMHGs) with intriguing properties such as self-healing, flexibility, responsiveness, and thermal and electrical conductivity. These properties significantly broaden their applications in various fields. This review introduces the featured performances of LMs, as well as emphatically summarizes advanced biomedical applications of LMHGs involving medical electronics, biomedical engineering, and soft electronics actuators. The present opportunities and challenges associated with the biological applications of LMHGs are also discussed. .

Transplacental transfer efficiency of maternal antibodies against influenza A(H1N1)pdm09 virus and dynamics of naturally acquired antibodies in Chinese children: a longitudinal, paired mother-neonate cohort study.

BACKGROUND: The 2009 pandemic H1N1 influenza A virus (A(H1N1)pdm09 virus) evolves rapidly and has continued to cause severe infections in children since its emergence in 2009. We aimed to characterise the kinetics of maternally and naturally acquired antibodies against historical A(H1N1)pdm09 strains and to assess the extent to which the response to heterologous strains following infection or vaccination affects observed A(H1N1)pdm09 strain-specific antibody titres in a Chinese paediatric population. METHODS: In this retrospective study, we used residual serum samples from 528 mother-neonate pairs from a non-interventional, longitudinal cohort study in southern China conducted from Sept 20, 2013, to Aug 24, 2018, from six local hospitals in Anhua County, Hunan Province, China. Mother-neonate pairs were eligible for inclusion if the neonates were born after Sept 20, 2013, and their mothers had resided in the study sites for at least 3 months. We tested samples with a haemagglutination inhibition (HAI) assay to measure antibody levels against three historical A(H1N1)pdm09 strains that were antigenically similar to the strains that circulated during the 2009 pandemic (A/Hunan-Kaifu/SWL4204/2009 [SWL4204/09 strain], A/Hunan-Daxiang/SWL1277/2016 [SWL1277/16 strain], and A/Hunan-Yanfeng/SWL185/2018 [SWL185/18 strain]). We also determined the seroprevalence, geometric mean titres (GMTs), transfer ratio of maternal antibodies, and the dynamics of maternally and naturally acquired antibodies in children, from birth to 3 years of age. FINDINGS: 1066 mother-neonate pairs were enrolled in the original cohort between Sept 20, 2013, and Oct 14, 2015. Of these, 528 pairs (523 mothers, 528 neonates) were selected for the present study. The median age of the mothers was 25 years (IQR 23 to 29). 291 (55%) of 528 children were boys and 237 (45%) were girls, and most children (452 [86%]) were breastfed before the age of 6 months. The GMTs and the seroprevalence for the SWL4204/09 strain were higher than those for the SWL1277/16 and SWL185/18 strains among mothers (GMTs: 10·4 [95% CI 9·8 to 11·1] vs 9·3 [8·7 to 9·8] vs 8·0 [7·5 to 8·4], p<0·0001; seroprevalence: 11·1% [95% CI 8·5 to 14·1] vs 6·9% [4·9 to 9·4] vs 4·6% [3·0 to 6·8], p=0·0003) and among neonates (GMTs: 10·7 [10·0 to 11·5] vs 9·4 [8·8 to 10·0] vs 8·1 [7·6 to 8·6], p<0·0001; seroprevalence: 13·4% [10·7 to 16·7] vs 8·7% [6·5 to 11·5] vs 6·1% [4·2 to 8·5], p=0·0002). Regardless of the A(H1N1)pdm09-specific strain, maternal antibodies could be transferred efficiently via the placenta (mean transfer ratios: 1·10 for SWL4204/09 vs 1·09 for SWL1277/16 vs 1·06 for SWL185/18; p=0·93). The A(H1N1)pdm09 strain-specific antibodies waned below the protective threshold of 1:40 within 2 months after birth. After maternal antibody waning, there were periodic increases and decreases in HAI antibody titres against three A(H1N1)pdm09 strains, and such increases were all significantly associated with a higher immune response to heterologous strains. Vaccination against the SWL4204/09 strain was associated with a poor response to the SWL185/18 strain (ß-0·20, 95% CI -0·28 to -0·13; p<0·0001). INTERPRETATION: Our findings suggest low pre-existing immunity against influenza A(H1N1)pdm09 virus among unvaccinated Chinese adult female and paediatric populations. This evidence, together with the rapid decay of maternal antibodies and the observed cross-reactivity among different A(H1N1)pdm09 strains, highlights the importance of accelerating maternal and paediatric influenza vaccination in China. FUNDING: The Key Program of the National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Prediction of extracapsular extension in prostate cancer using the Likert scale combined with clinical and pathological parameters.

Abstract: This study aimed to investigate the independent clinical, pathological, and radiological factors associated with extracapsular extension in radical prostatectomy specimens and to improve the accuracy of predicting extracapsular extension of prostate cancer before surgery. Methods: From August 2018 to June 2023, the clinical and pathological data of 229 patients with confirmed prostate cancer underwent radical prostatectomy from The Second Hospital of Yinzhou. The patients' multiparametric magnetic resonance imaging data were graded using the Likert scale. The chi-square or independent-sample T-test was used to analyze the related factors for an extracapsular extension. Multivariate analysis was used to identify independent factors associated with extracapsular extension in prostate cancer. Additionally, receiver operating characteristic curve analysis was used to calculate the area under the curve and assess the diagnostic performance of our model. The clinical decision curve was used to analyze the clinical net income of Likert scale, biopsy positive rate, biopsy GG, and combined mode. Results: Of the 229 patients, 52 had an extracapsular extension, and 177 did not. Multivariate analysis showed that the Likert scale score, biopsy grade group and biopsy positive rate were independent risk factors for extracapsular extension in prostate cancer. The area under the curves for the Likert scale score, biopsy grade group, and biopsy positive rate were 0.802, 0.762, and 0.796, respectively. Furthermore, there was no significant difference in the diagnostic efficiency for extracapsular extension (P>0.05). However, when these three factors were combined, the diagnostic efficiency was significantly improved, and the area under the curve increased to 0.905 (P<0.05). In the analysis of the decision curve, The clinical net income of the combined model is obviously higher than that of Likert scale, biopsy positive rate, and biopsy GG. Conclusion: The Likert scale, biopsy grade group and biopsy positive rate are independent risk factors for extracapsular extension in prostate cancer, and their combination can significantly improve the diagnostic efficiency for an extracapsular extension.

Localization of multiple DNAzymes as a branchedzyme-powered nanodevice for the immunoassay of tumor biomarkers.

Traditional immunoassay methods often face challenges due to the labeling procedure of protein enzymes, the use of multiple antibodies, and severe conditions. To address these limitations, we propose the concept of incorporating branchedzyme-powered nanodevices into immunoassays. In this strategy, multiple DNAzymes are localized onto gold nanoparticles (AuNPs) along with substrates. The localization format facilitates intramolecular reactions between DNAzymes and substrates, leading to accelerated kinetics of the nanodevice. Upon the formation of an immunocomplex with an antibody on a 96-well plate, the branchedzyme-powered nanodevice catalytically releases multiple fluorescent signals under ambient temperature, eliminating the need for secondary antibodies. The branched DNAzymes exhibit catalytic properties similar to those of protein enzymes, thus simplifying the assay procedure and achieving isothermal detection. Furthermore, the detection process can be controlled by the addition or deletion of cofactors. Additionally, the affinity ligand can be easily modified to construct nanodevices specific to different targets without requiring extensive redesign. This strategy has demonstrated successful quantification of tumor biomarkers such as alpha-fetoprotein (AFP) and prostate-specific antigen (PSA) at subpicomolar concentrations, showcasing its suitability for clinical applications. Consequently, the branchedzyme-powered nanodevice represents a valuable addition to the immunoassay toolbox, opening new possibilities for clinical diagnostics.

Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection.

Enterovirus A71 (EV-A71) infection is a major cause of severe hand, foot and mouth disease (HFMD) in young children. The characteristics of EV-A71 neutralizing antibodies in HFMD patients are not well understood. In this study, we identified and cloned EV-A71-neutralizing antibodies by single cell RNA and B cell receptor sequencing of peripheral blood mononuclear cells. From 145 plasmablasts, we identified two IgG1 monoclonal antibodies (mAbs) and six IgM mAbs that neutralized EV-A71. Four of the IgM mAbs harbor germline variable sequences and neutralize EV-A71 potently. Two genetically similar IgM antibodies from two patients have recurrent heavy chain variable domain gene usage and similar complementarity-determining region 3 sequences. We mapped the residues of EV-A71 critical for neutralization through selection of virus variants resistant to antibody neutralization in the presence of neutralizing mAbs. The residues critical for neutralization are conserved among EV-A71 genotypes. Epitopes for the two genetically similar antibodies overlap with the SCARB2 binding site of EV-A71. We used escape variants to measure the epitope-specific antibody response in acute phase serum samples from EV-A71 infected HFMD patients. We found that these epitopes are immunogenic and contributed to the neutralizing antibody response against the virus. Our findings advance understanding of antibody response to EV-A71 infection in young children and have translational potential: the IgM mAbs could potentially be used for prevention or treatment of EV-A71 infections.

[A V-Y shaped flap with digital artery nerve at metacarpophalangeal joint was used to repair the defect of middle and distal phalanx].

OBJECTIVE: To explore a surgical method for the reconstruction of volar soft tissue defect and sensory and vascular repair in middle and far phalangeal digits. METHODS: From January 2016 to January 2020, a total of 14 patients , 9 males and 5 females, ages ranging from 22 to 69 years old, and with volar soft tissue defects in the middle and distal digits 2 to 4, underwent surgical reconstruction using the V-Y shaped flap with digital artery and nerve at the metacarpophalangeal joint. The defect area was (2.0~2.5) cm×(1.5 ~2.0) cm. The procedure involved the harvest of a V-Y shaped flap with the digital artery and nerve from the metacarpophalangeal joint. Flap design, dissection of blood vessels and nerves, and anastomosis with the digital artery and nerve were performed according to a standardized protocol., Functional exercise of affected finger was initiated 3 weeks postoperatively. Subsequent assessments were conducted to evaluate finger pulp sensation, shape and other relevant parameters. According to the upper extremity functional evaluation standard set up by Hand Surgery Branch of Chinese Medical Association, the surgical outcomes were evaluated. RESULTS: All 14 cases demonstrated successful tissue transplantation, , with immediate recovery of sensation observed in 10 cases with distal finger pulp defects. Four patients with middle phalangeal defects experienced gradual sensory recovery within 2 to 3 months postoperatively. Thirteen patients were followed up for a mean duration of (8.8 ± 4.49) months, during which satisfactory outcomes were observed. The average two-point resolution of the finger pulp was 4-6mm, and sensory function evaluation yielded a score of S3 or above. Patients exhibited realistic finger shape, normal skin color and temperature, good wear resistance, and cold resistance. Furthermore, finger joint function was essentially normal. CONCLUSION: The V-Y shaped flap with digital artery and nerve at the metacarpophalangeal joint offers a suitable solution for repairing the defect of the middle or distal phalangeal finger. This technique is characterized by its simplicity, low risk, and favorable outcomes, including restored finger shape, blood supply and sensation. Moreover, high patient satisfaction was achieved.

Identifying relevant diffusion MRI microstructure biomarkers relating to exposure to repeated head impacts in contact sport athletes.

PURPOSE: Repeated head impacts (RHI) without concussion may cause long-term sequelae. A growing array of diffusion MRI metrics exist, both empiric and modeled and it is hard to know which are potentially important biomarkers. Common conventional statistical methods fail to consider interactions between metrics and rely on group-level comparisons. This study uses a classification pipeline as a means towards identifying important diffusion metrics associated with subconcussive RHI. METHODS: 36 collegiate contact sport athletes and 45 non-contact sport controls from FITBIR CARE were included. Regional/whole brain WM statistics were computed from 7 diffusion metrics. Wrapper-based feature selection was applied to 5 classifiers representing a range of learning capacities. Best 2 classifiers were interpreted to identify the most RHI-related diffusion metrics. RESULTS: Mean diffusivity (MD) and mean kurtosis (MK) are found to be the most important metrics for discriminating between athletes with and without RHI exposure history. Regional features outperformed global statistics. Linear approaches outperformed non-linear approaches with good generalizability (test AUC 0.80-0.81). CONCLUSION: Feature selection and classification identifies diffusion metrics that characterize subconcussive RHI. Linear classifiers yield the best performance and mean diffusion, tissue microstructure complexity, and radial extra-axonal compartment diffusion (MD, MK, De,⊥) are found to be the most influential metrics. This work provides proof of concept that applying such approach to small, multidimensional dataset can be successful given attention to optimizing learning capacity without overfitting and serves an example of methods that lead to better understanding of the myriad of diffusion metrics as they relate to injury and disease.

A simple strategy based on combinatorial gold nanoparticle sizes for enhanced sensitivity in colorimetric bioanalysis.

Taking advantage of salt-induced aggregation, gold nanoparticles (AuNPs) have been intensively employed in non-cross-linking strategies (NCLs) for colorimetric bioanalysis. Such a classical method is popular due to its simplicity and cost-effectiveness, but it still suffers from poor sensitivity in analytical practice. To address this issue, we simply mixed the four sizes of non-functional AuNPs (10 nm/20 nm/30 nm/40 nm) to establish a highly sensitive combinatorial system in a non-cross-linking strategy (cNCL). For comparison, we also designed four independent systems with individual sizes of AuNPs (10 nm, 20 nm, 30 nm and 40 nm, respectively) as typical non-cross-linking strategies (tNCLs). Interestingly, the cNCLs were found to have significantly enhanced sensitivity compared to each of the tNCLs in analytical performance. TEM and theoretical calculation were employed to explore this phenomenon, and it is indicated that the aggregation behaviours of cNCLs show more compact morphology by particle-to-particle stacking. We then tuned the size proportions of various AuNPs in cNCLs to evaluate the contribution of each size of the AuNPs. It appears that 10 nm AuNPs are mainly responsible for minimizing background intensity, and 40 nm AuNPs for maximizing signal intensity. Moreover, with the well-studied effect of combinatorial AuNP sizes in cNCLs, an excellent signal-to-background (S/B) ratio can be obtained, achieving at least 500-fold and 2.5-fold improvement in the aspects of optical and visual sensitivity, respectively. Such a combinatorial AuNP size-based NCL (cNCL) strategy is modification-free towards AuNPs, and the whole process can be accomplished within 10 min. The aggregation behaviour significantly impacts the optical properties and morphology, and therefore improves analytical sensitivity. With these findings, valuable insight is provided in developing sensitive and versatile colorimetric assays based on classic AuNP aggregation.

Guanidine-based biomimetic hydrides for carbon dioxide reduction.

The feasibility of various bespoke guanidine-based compounds as biomimetic hydrides were assessed by Density Functional Theory (DFT). The results predicted that tricyclic pentanidine hydrides are viable candidates to reduce CO2 to HCOO- and be regenerated electrochemically, demonstrating a recyclable and sustainable method to achieve metal-free electrochemical reduction of CO2.

Identification of three metabolic subtypes in gastric cancer and the construction of a metabolic pathway-based risk model that predicts the overall survival of GC patients.

Gastric cancer (GC) is highly heterogeneous and GC patients have low overall survival rates. It is also challenging to predict the prognosis of GC patients. This is partly because little is known about the prognosis-related metabolic pathways in this disease. Hence, our objective was to identify GC subtypes and genes related to prognosis, based on changes in the activity of core metabolic pathways in GC tumor samples. Differences in the activity of metabolic pathways in GC patients were analyzed using Gene Set Variation Analysis (GSVA), leading to the identification of three clinical subtypes by non-negative matrix factorization (NMF). Based on our analysis, subtype 1 showed the best prognosis while subtype 3 exhibited the worst prognosis. Interestingly, we observed marked differences in gene expression between the three subtypes, through which we identified a new evolutionary driver gene, CNBD1. Furthermore, we used 11 metabolism-associated genes identified by LASSO and random forest algorithms to construct a prognostic model and verified our results using qRT-PCR (five matched clinical tissues of GC patients). This model was found to be both effective and robust in the GSE84437 and GSE26253 cohorts, and the results from multivariate Cox regression analyses confirmed that the 11-gene signature was an independent prognostic predictor (p < 0.0001, HR = 2.8, 95% CI 2.1-3.7). The signature was found to be relevant to the infiltration of tumor-associated immune cells. In conclusion, our work identified significant GC prognosis-related metabolic pathways in different GC subtypes and provided new insights into GC-subtype prognostic assessment.