Microscopic Insight Of Molecularly Imprinted Sol-Gel Matrix For Creatinine-Recognised Biosensor

Molecularly imprinted polymer (MIP) is important in biomimetic recognition systems owing to its selective molecular recognition towards any guest of interest. Considering the exceptional thermal, chemical and mechanical tolerance under a wide variety of conditions, MIP has been one of the potential “smart” devices in biomedical applications, such as pharmaceutical industry, clinical analysis and in vivo or in vitro sensing. However, one of the major issues that challenges MIP lies on the conformational adaptability of MIP. As compared to the conventional biomedical diagnostics, such as enzyme-linked immunosorbent assay (ELISA), the difficulties in controlling the shape-specificity or molecular memory within MIP for the best molecular fitting has restricted the potential of MIP as a sensing tool. In fact, the optimal morphological integrity is the key factor to define the successful sensing activity by MIP. As such, the present study intends to furnish the key concepts of molecular imprinting, particularly the underlying mechanisms of MIP beyond the usual description of molecular recognition. First, the host-guest chemistry is studied in detail, in terms of intermolecular interactions, to elucidate the recognition behaviour of target molecule (template), creatinine (Cre) by MIP. Cre is a spontaneous and non-enzymatic degradation end product of creatine (Cr) or phosphocreatine metabolism in vertebrates, which serves as a reliable biomarker in assessing renal, thyroid and muscular dysfunction. In this study, the imprinting of Cre is ascertained via sharing of lone pair electrons from nitrogen (N) atom of Cre and oxygen (O) atoms of the sol-gel matrix, respectively, to the Al3+ Lewis acid. To further fortify the shape memory stiffness of MIP, Cre is removed from the organised architecture by a series of eluents via physical means, leaving behind a binding framework with varying steric and functional complementarity to Cre. Referring to the experimental data, the best Cre-molecular memory is imparted by methanol eluent, making MIP capable of selective uptake of Cre up to 19.48 ± 0.64 mg g−1 MIP even in the presence of functionally alike, i.e., Cr, and/or structurally alike interfering analogues, i.e., N-hydroxysuccinimide (N-hyd) and 2-pyrrolidinone (2-pyr), by competitive selectivity coefficients of 3.01 ± 1.11, 3.75 ± 0.57 and 5.24 ± 4.59, respectively. Coupled with the powerful and reliable prediction of chemical properties for biomolecular system, the MIP system is rationalised with the aid of a computational chemistry tool, HyperChem based on the Parameterised Model number 3 (PM3) semi-empirical quantum mechanics method. The molecular modelling has come up with a good agreement between the theoretical computations and the empirical data, which extends the validity of computational screening in the MIP system in an experimental-free approach. Finally, the MIP is film-coated on carbon electrode as an integrated biosensor that translates the chemical response from Cre into an electroanalytical response, reaching ca. 1.4 µA. During artificial urinary sampling, the Cre-MIP film electrode outperforms in the binary mixture analysis, attaining an empirical binary I at 1.4823 ±0.0267 µA for Cre:Cr at 80:20 molar ratio. It is noteworthy that molecular imprinting has once again proven its feasibility in Cre-MIP biosensor through the electrochemical sensing performance. Henceforth, this study has come up with a practical design of MIP for the detection of renal dysfunction by point-of-care testing for Cre

SphereFed: Hyperspherical Federated Learning

Federated Learning aims at training a global model from multiple decentralized devices (i.e. clients) without exchanging their private local data. A key challenge is the handling of non-i.i.d. (independent identically distributed) data across multiple clients that may induce disparities of their local features. We introduce the Hyperspherical Federated Learning (SphereFed) framework to address the non-i.i.d. issue by constraining learned representations of data points to be on a unit hypersphere shared by clients. Specifically, all clients learn their local representations by minimizing the loss with respect to a fixed classifier whose weights span the unit hypersphere. After federated training in improving the global model, this classifier is further calibrated with a closed-form solution by minimizing a mean squared loss. We show that the calibration solution can be computed efficiently and distributedly without direct access of local data. Extensive experiments indicate that our SphereFed approach is able to improve the accuracy of multiple existing federated learning algorithms by a considerable margin (up to 6% on challenging datasets) with enhanced computation and communication efficiency across datasets and model architectures.Comment: European Conference on Computer Vision 202

Effects of periarticular injection on analgesic effects and NSAID use in total knee arthroplasty and total hip arthroplasty

OBJECTIVES: This study examined periarticular multimodal drug injection and the use of nonsteroidal anti-inflammatory drugs for an early analgesic effect after total knee arthroplasty and total hip arthroplasty. Patient satisfaction and benefits from the treatment were also assessed. METHODS: A total of 110 patients who were scheduled to undergo total knee arthroplasty and 86 patients who were scheduled to undergo total hip arthroplasty were divided into two groups, the study group and the control group. The study group received a periarticular multimodal drug injection during surgery. The control group received an equal volume of normal saline. All patients received an analgesia pump and a moderate dose of nonsteroidal anti-inflammatory drugs. Resting and motion Numeric Rating Scale scores, the Western Ontario and McMaster Universities Arthritis Index, knee or hip joint range of motion, length of postoperative hospital stay, patient satisfaction, total nonsteroidal anti-inflammatory drug consumption and side effects were recorded. RESULTS: Both study groups exhibited significant improvement in pain Numeric Rating Scale scores during rest and exercise several days after the surgery. The range of joint motion was greater in the study group, and the length of postoperative hospital stay was shorter than that in the control group. Patients in the study group consumed fewer nonsteroidal anti-inflammatory drugs and reported greater satisfaction with surgery. CONCLUSION: Intraoperative periarticular multimodal drug injection significantly relieved pain after surgery and reduced nonsteroidal anti-inflammatory drug consumption. These patient had a better postoperative experience, including satisfaction and rehabilitation

Don’t Worry Be Happy

Understanding the influences of happiness allows countries to focus resources on the best happiness contributors. This paper studies the effect of Gross Domestic Product (GDP) and social spending, in terms of education and healthcare, on a population’s happiness. Data analysis through linear regression shows that as GDP increases, happiness increases; however this only seems to apply to countries that are developing. Once the GDP hits a threshold, around USD 10,000, it has little effect on the country’s happiness. The paper builds upon past research on public happiness in relation to GDP and social expenditure and informing public policies

Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1β) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed

Study on failure mechanism and application of double-layer structure floor with large buried depth and high confined water

The first mining of nearly whole rock lower protective layer working face in Pingdingshan coal mining area is used to liberate the Ji group coal resources of its upper threatened by the gas outburst. The mining of the rock layer at a depth of nearly 1000 meters is bound to increase the depth of the floor damage. Once the L5 weak water-rich aquifer in the aquifuge is disturbed, the indirect recharge channel of the cold ash water is formed, which affects the safety and stability of the rock floor. Firstly, the theoretical model of plastic slip line of double-layer structure floor is established, and the analytical solution of maximum failure depth of double-layer floor under three working conditions is derived. Then through the self-designed similar simulation experimental platform of pore water pressure (spring) and stratum effective stress (jack), the deformation form and failure characteristics of stope roof and floor are simulated and analyzed based on digital image correlation technology. Finally, the borehole strain measurement method was used to carry out on-site monitoring of floor fracture development morphology in Ji15-31040 nearly whole rock working face of Pingdingshan No.12 Coal Mine. The results show that the maximum failure depth of Ji15-31040 nearly whole rock working face floor is 16.59 m by using the plastic slip line theory of double-layer structure floor. The similar simulation experiment reveals that the floor failure is concentrated at both ends of the open-off cut and the working face, with obvious lagging failure characteristics. The maximum failure depth is 17.8 m. After the working face advances 159.9 m into full mining, the floor stress gradually recovers. The field measurement results show that the floor rock mass has a compression-shear slip failure at 7.9 m in front of the working face. The floor before and after the working face is pushed through the borehole shows compression-shear and tension-shear failure, respectively. The maximum failure depth of the floor is between 16.5 m and 18 m. The results of field measurement are in good agreement with theoretical calculation and similar simulation test

Immune Infiltration in Atherosclerosis is Mediated by Cuproptosis-Associated Ferroptosis Genes

Aims: In this study, we aimed to identify cuproptosis-associated ferroptosis genes in the atherosclerosis microarray of the Gene Expression Omnibus (GEO) database and to explore hub gene-mediated immune infiltration in atherosclerosis.Background: Immune infiltration plays a crucial role in atherosclerosis development. Ferroptosis is a mode of cell death caused by the iron-dependent accumulation of lipid peroxides. Cuproptosis is a recently discovered type of programmed cell death. No previous studies have examined the mechanism of cuproptosis-associated ferroptosis gene regulation in immune infiltration in atherosclerosis.Methods: We searched the qualified atherosclerosis gene microarray in the GEO database, integrated it with ferroptosis and cuproptosis genes, and calculated the correlation coefficients. We then obtained the cuproptosis-associated ferroptosis gene matrix and screened differentially expressed genes. Subsequently, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and protein–protein interaction network analysis of differentially expressed genes. We also screened hub genes according to the Matthews correlation coefficient (MCC) algorithm. We conducted enrichment analysis of hub genes to explore their functions and predict related microRNAs (P<0.05). We also used the single-sample gene set enrichment analysis (ssGSEA) algorithm to analyze the relationships between hub genes and immune infiltration, and used immune-associated hub genes to construct a risk model. Finally, we used the drug prediction results and molecular docking technology to explore potential therapeutic drugs targeting the hub genes.Results: Seventy-eight cuproptosis-associated ferroptosis genes were found to be involved in the cellular response to oxidative and chemical stress, and to be enriched in multiple pathways, including ferroptosis, glutathione metabolism, and atherosclerosis. Ten hub genes were identified with the MCC algorithm; according to the ssGSEA algorithm, these genes were closely associated with immune infiltration, thus indicating that cuproptosis-associated ferroptosis genes may participate in atherosclerosis by mediating immune infiltration. The receiver operating characteristic curve indicated that the model had a good ability to predict atherosclerosis risk. The results of drug prediction (adjusted P<0.001) and molecular docking showed that glutathione may be a potential therapeutic drug that targets the hub genes.Conclusion: Cuproptosis-associated ferroptosis genes are associated with immune infiltration in atherosclerosis

Surface skyrmions and dual topological Hall effect in antiferromagnetic topological insulator EuCd2_2As2_2

In this work, we synthesized single crystal of EuCd$_2$As$_2$, which exhibits A-type antiferromagnetic (AFM) order with in-plane spin orientation below $T_N$ = 9.5~K.Optical spectroscopy and transport measurements suggest its topological insulator (TI) nature with an insulating gap around 0.1eV. Remarkably, a dual topological Hall resistivity that exhibits same magnitude but opposite signs in the positive to negative and negative to positive magnetic field hysteresis branches emerges below 20~K. With magnetic force microscopy (MFM) images and numerical simulations, we attribute the dual topological Hall effect to the N\'{e}el-type skyrmions stabilized by the interactions between topological surface states and magnetism, and the sign reversal in different hysteresis branches indicates potential coexistence of skyrmions and antiskyrmions. Our work uncovers a unique two-dimensional (2D) magnetism on the surface of intrinsic AFM TI, providing a promising platform for novel topological quantum states and AFM spintronic applications.Comment: 7 pages, 3 figure

Algorithm for prediction of tumour suppressor p53 affinity for binding sites in DNA

The tumour suppressor p53 is a transcription factor that binds DNA in the vicinity of the genes it controls. The affinity of p53 for specific binding sites relative to other DNA sequences is an inherent driving force for specificity, all other things being equal. We measured the binding affinities of systematically mutated consensus p53 DNA-binding sequences using automated fluorescence anisotropy titrations. Based on measurements of the effects of every possible single base-pair substitution of a consensus sequence, we defined the DNA sequence with the highest affinity for full-length p53 and quantified the effects of deviation from it on the strength of protein–DNA interaction. The contributions of individual nucleotides were to a first approximation independent and additive. But, in some cases we observed significant deviations from additivity. Based on affinity data, we constructed a binding predictor that mirrored the existing p53 consensus sequence definition. We used it to search for high-affinity binding sites in the genome and to predict the effects of single-nucleotide polymorphisms in these sites. Although there was some correlation between the Kd and biological function, the spread of the Kds by itself was not sufficient to explain the activation of different pathways by changes in p53 concentration alone

Can Measuring the ‘Dual Anchors of Aorta’ Enhance the Success Rate of TAVR?—A Single-Center Experience

Introduction: Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study’s primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients. Methods: The study enrolled retrospectively and prospectively patients diagnosed with severe AR who eventually underwent TAVR procedure from January 2019 to September 2022 at Fuwai cardiovascular Hospital, Beijing. Baseline information, MDCT measurements, anatomical classification, perioperative, and 1-year follow-up outcomes were collected and analyzed. Based on a novel anatomical categorization and dual anchoring theory, patients were divided into four categories according to the level of anchoring area. Type 1, 2, and 3 patients (with at least two anchoring regions) will receive TAVR with a transcatheter heart valve (THV), but Type 4 patients (with zero or one anchoring location) will be deemed unsuitable for TAVR and will instead receive medical care (retrospectively enrolled patients who already underwent TAVR are an exception). Results: The mean age of the 37 patients with severe chronic AR was 73.1 ± 8.7 years, and 23 patients (62.2%) were male. The American Association of Thoracic Surgeons’ score was 8.6 ± 2.1%. The MDCT anatomical classification included 17 cases of type 1 (45.9%), 3 cases of type 2 (8.1%), 13 cases of type 3 (35.1%), and 4 cases of Type 4 (10.8%). The VitaFlow valve (MicroPort, Shanghai, China) was implanted in 19 patients (51.3%), while the Venus A valve (Venus MedTech, Hangzhou, China) was implanted in 18 patients (48.6%). Immediate TAVR procedural and device success rates were 86.5% and 67.6%, respectively, while eight cases (21.6%) required THV-in-THV implantation, and nine cases (24.3%) required permanent pacemaker implantation. Univariate regression analysis revealed that the major factors affecting TAVR device failure were sinotubular junction diameter, THV type, and MDCT anatomical classification (p &lt; 0.05). Compared with the baseline, the left ventricular ejection fraction gradually increased, while the left ventricular end-diastolic diameter remained small, and the N-terminal-pro hormone B-type natriuretic peptide level significantly decreased within one year. Conclusion: According to the results of our study, TAVR with a self-expanding THV is safe and feasible for patients with chronic severe AR, particularly for those who meet the criteria for the appropriate MDCT anatomical classification with intact dual aortic anchors, and it has a significant clinical effect for at least a year.</p