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Objective: To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism. Methods: AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis. Results: The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05). Conclusions: MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP. [ABSTRACT FROM AUTHOR]

Background: Although several pharmacoeconomic studies have assessed the cost-effectiveness of maintenance immunosuppressive regimens for heart transplant recipients, economic comparisons between various combination drug therapies remain sparse. Aim: This study used an economic evaluation based on network meta-analysis to assess the cost-effectiveness of four immunosuppressive regimens for adult heart transplant recipients in China. Method: We conducted a systematic search for clinical trials in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP database. A validated Markov model was adapted to reflect the Chinese medical landscape. Four maintenance immunosuppression regimens were considered: tacrolimus/mycophenolate mofetil (TAC/MMF), cyclosporine/mycophenolate mofetil (CSA/MMF), everolimus/cyclosporine (EVL/CSA), and sirolimus/tacrolimus (SRL/TAC). The probabilities of health events were derived from a comprehensive literature review. Direct medical costs, adjusted for 2022 values, were from public documents and websites, while utilities for quality-adjusted life-years (QALYs) were taken from previous studies. Primary outcomes were mean lifetime cost, QALYs, and cost-effectiveness, with a willingness-to-pay (WTP) threshold set at three times China's GDP per capita in 2022. Sensitivity analyses were conducted to test the robustness of the results. Results: The base case analysis identified TAC/MMF as the most cost-effective regimen, producing a mean of 6.31 QALYs per patient at a cost of Chinese Yuan (CNY) 534,182.89. Sensitivity analyses consistently reinforced TAC/MMF as the most cost-effective and robust choice. Conclusion: TAC/MMF is the most cost-effective maintenance immunosuppressive regimen for heart transplant recipients within the Chinese health system. The study findings are reinforced by sensitivity analyses, affirming their robustness amid various uncertainties. [ABSTRACT FROM AUTHOR]

We conducted a series tests on surface layers of plateau concrete at the ages of 180 and 540 days, including the most superficial cement paste, the 5 mm thick surface mortar, and the 50 mm thick surface concrete. Thermogravimetry and nitrogen absorption porosimetry on cement past, mercury intrusion porosimetry on mortar, and microhardness test on interface transition zone between mortar and coarse aggregate were conducted to evaluate the hydration degree and characterize the micro-structure. Whilst, tests for the rebound strength, abrasion resistance, and chloride ion impenetrability of concrete were conducted to assess the macroperformance. The experimental results show that, affected by the harsh plateau climate, outward surfaces have lower hydration degrees and worse pore structure than inward surfaces. As the hydration of concrete surface is ongoing after the age of 180 days, both the micro-structure and the macro-performance are continuously improved. In the long-term, either the orientation or the depth towards surface does not significantly affect concrete performance. Surface carbonation brings positive effects on mechanical properties but negative effects on the durability. Additionally, standard test result of chloride ion impenetrability is found significantly affected by the atmospheric pressure. For a same batch of concrete, charge passed in plateau regions is obviously lower than that in common regions. [ABSTRACT FROM AUTHOR]

Introduction: This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG). Methods: Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a ≥ 3- or ≥ 5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA. Results: Efgartigimod IV had the lowest NNT versus placebo for achieving a ≥ 3- and ≥ 5-point reduction in QMG, as well as a ≥ 5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a ≥ 3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors. Conclusions: FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit–risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+ gMG. [ABSTRACT FROM AUTHOR]

Shared services have become an important IT-enabled organizational form for providing support business functions to internal users. The information systems that implement and deliver shared services are part of the organizational IT infrastructure that has a twofold effect on firm financial performance. On the one hand, with the shared services model, the IT infrastructure consolidates so that the costs are lowered for providing the common functions firm-wide. On the other hand, the systems delivering the shared services embody the workflow and business functions so that the value of shared services can be gained from improvements in the function performance at the process level. We perceive finance shared services as IT-enabled services for corporate finance and accounting functions, and propose that finance shared services improve firm profitability via cost savings at firm level and via increased working capital efficiency at the process level. We test our hypotheses with data on Chinese public firms from 2008 to 2019. Data analysis results show both direct effect of finance shared services on profitability and mediating effect of working capital efficiency. This study expands our understandings about impacts of shared services, and contributes to empirical research in IT business value. [ABSTRACT FROM AUTHOR]

We conducted a large-scale whole-brain morphometry study by analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We registered 204 mouse brains of three major imaging modalities to the Allen Common Coordinate Framework (CCF) atlas, annotated 182,497 neuronal cell bodies, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1876 neurons along with their axonal motifs, and detected 2.63 million axonal varicosities that indicate potential synaptic sites. Our analyzed six levels of information related to neuronal populations, dendritic microenvironments, single-cell full morphology, dendritic and axonal arborization, axonal varicosities, and sub-neuronal structural motifs, along with a quantification of the diversity and stereotypy of patterns at each level. This integrative study provides key anatomical descriptions of neurons and their types across a multiple scales and features, contributing a substantial resource for understanding neuronal diversity in mammalian brains. Here the authors analyzed 3.7 petavoxels of 3D imaging data from 204 mouse brains, aiming to comprehensively characterize diverse morphological and modular patterns conserved across six spatial scales of mouse brain anatomy, ranging from the whole-brain scale to synaptic levels. [ABSTRACT FROM AUTHOR]

The ability to lubricate and resist wear at temperatures above 600 °C in an oxidative environment remains a significant challenge for metals due to their high-temperature softening, oxidation, and rapid degradation of traditional solid lubricants. Herein, we demonstrate that high-temperature lubricity can be achieved with coefficients of friction (COF) as low as 0.10-0.32 at 600-900 °C by tailoring surface oxidation in additively-manufactured Inconel superalloy. By integrating high-temperature tribological testing, advanced materials characterization, and computations, we show that the formation of spinel-based oxide layers on superalloy promotes sustained self-lubrication due to their lower shear strength and more negative formation and cohesive energy compared to other surface oxides. A reversible phase transformation between the cubic and tetragonal/monoclinic spinel was driven by stress and temperature during high temperature wear. To span Ni- and Cr-based ternary oxide compositional spaces for which little high-temperature COF data exist, we develop a computational design method to predict the lubricity of oxides, incorporating thermodynamics and density functional theory computations. Our finding demonstrates that spinel oxide can exhibit low COF values at temperatures much higher than conventional solid lubricants with 2D layered or Magnéli structures, suggesting a promising design strategy for self-lubricating high-temperature alloys. The authors develop an approach for enhancing the wear resistance and lubricity of metals at elevated temperatures of in oxidative environments, where traditional solid lubricants fail. By engineering surface oxidation in additively manufactured Inconel, they achieve low friction coefficients, between 0.10 and 0.32 at 600-900 °C, through the formation of a spinel-based oxide layer. [ABSTRACT FROM AUTHOR]

The metabolic reprogramming of macrophages is a potential therapeutic strategy for sepsis treatment, but the mechanism underlying this reprogramming remains unclear. Since glycolysis can drive macrophage phenotype switching, the rate-limiting enzymes in glycolysis may be key to treating sepsis. Here, we found that, compared with other isoenzymes, the expression of 6-phosphofructokinase, muscle type (PFKM) was the most upregulated in monocytes from septic patients. Recombinant thrombomodulin (rTM) treatment downregulated the protein expression of PFKM in macrophages. Both rTM treatment and Pfkm knockout protected mice from sepsis and reduced the production of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and IL-27, whereas PFKM overexpression increased the production of these cytokines. Mechanistically, rTM treatment inhibited glycolysis in macrophages by decreasing PFKM expression in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. HIF-1α overexpression increased methyltransferase-like 3 (METTL3) expression, elevated the m6A level on Pfkm, and upregulated the protein expression of PFKM. METTL3 silence attenuated HIF-1α-mediated PFKM expression. These findings provide insight into the underlying mechanism of macrophage reprogramming for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

Background: Targeting the STAT3 signaling pathway is a promising therapeutic approach for cancer patients. However, the association between STAT3 expression, the tumor immune microenvironment, and genetic variation remains unclear across human cancers, especially prostate cancer. Methods: We used R software and other tools to analyze pan-cancer and mutation data from publicly available databases statistically. A comprehensive investigation was performed to assess the genetic heterogeneity and clinical relevance of STAT3 in various malignancies, with a specific focus on its role in the immune landscape and prognostic significance in prostate cancer. The findings were validated through immunohistochemistry (IHC) and multiplex immunofluorescence (mIF). Results: STAT3 expression is abnormal in the majority of cancer tissues, which is strongly correlated with these patients' prognosis. Eight measures of tumor heterogeneity and six measures of tumor stemness of multiple tumor types showed a strong correlation with STAT3 expression. Furthermore, in individuals with prostate cancer, STAT3 expression indicated the degree of immune cell infiltration and the advancement of the disease. IHC analysis revealed that STAT3 was down-regulated in prostate tumor tissues, while mIF analysis demonstrated that STAT3 signaling (p-STAT3) was extensively active in tumor tissues and positive lymph node tissues. Conclusion: STAT3 may serve as a valuable prognostic biomarker and therapeutic target across various cancers, with particular relevance to prostate cancer. [ABSTRACT FROM AUTHOR]

Bismuth microspheres@N-doped porous carbon anode (Bi@NPC-2) is rational designed and successfully prepared by an easy one-pot heat treatment process. The composite demonstrated superior sodium storage performance, including excellent cyclic stability of 326.4 mAh g−1 after 4000 cycles at 5 A g−1 with a capacity retention of 95% and ultra-high rate capability of 286.7 mAh g−1 at a high current rate of 40 A g−1. This excellent performance is mainly due to the unique material design, the three-dimensional porous structure not only helps to mitigate the volume expansion of bismuth, but also shortens the diffusion path of sodium ions. In addition, nitrogen doping improves the conductivity of the electrode and provides more active sites for sodium storage. More importantly, the preparation process is simple, and the raw materials used are cheap, thus the Bismuth microspheres@N-doped porous carbon composite shows important practical large-scale applications. This one-step sintering method can also be applied to other alloy-based sodium storage materials. [ABSTRACT FROM AUTHOR]

An electrochemical biosensor was created to identify the liver cancer marker alpha-fetoprotein (AFP) by employing nanocomposite materials. A combination of reduced graphene oxide (rGO) and molybdenum disulfide (MoS2) was selected as the substrate material for the sensor to prepare the PtNPs/MoS2@rGO electrochemical immunosensor. Among them, rGO has strong conductivity and MoS2 provides a large surface area for the anchoring of PtNPs for better attachment to the hybridized nanomaterials. Meanwhile, PtNPs exhibit consistent biocompatibility and excellent electrocatalytic activity. PtNPs also attach to hybrid nanomaterials and bind the antibody via the Pt–S bond, thereby furnishing the antibody with multiple binding sites for enhanced antibody adhesion. The immunosensor achieved ultra-sensitive AFP detection by exploiting the specific antigen–antibody binding. The structure and morphology of the PtNPs/MoS2@rGO composites were investigated by transmission electron microscopy (TEM), energy dispersive X-ray (EDS) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy, and the sensor was electrochemically characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, using differential pulse voltammetry the biosensor detected AFP in serum within a linear range of 1 ~ 105 pg/mL, with a correlation coefficient (r2) of 0.9989, and a detection limit of 0.12 pg/mL (S/N = 3). The method offers a new approach for the ultrasensitive detection of serum AFP and is extremely selective, accurate, and precise with a relative standard deviation (RSD) of less than 6%. It has been successfully applied to the analysis of real human blood samples. [ABSTRACT FROM AUTHOR]

Spatial transcriptomics technologies with high resolution often lack high sensitivity in mRNA detection. Here we report a dendrimeric DNA coordinate barcoding design for spatial RNA sequencing (Decoder-seq), which offers both high sensitivity and high resolution. Decoder-seq combines dendrimeric nanosubstrates with microfluidic coordinate barcoding to generate spatial arrays with a DNA density approximately ten times higher than previously reported methods while maintaining flexibility in resolution. We show that the high RNA capture efficiency of Decoder-seq improved the detection of lowly expressed olfactory receptor (Olfr) genes in mouse olfactory bulbs and contributed to the discovery of a unique layer enrichment pattern for two Olfr genes. The near-cellular resolution provided by Decoder-seq has enabled the construction of a spatial single-cell atlas of the mouse hippocampus, revealing dendrite-enriched mRNAs in neurons. When applying Decoder-seq to human renal cell carcinomas, we dissected the heterogeneous tumor microenvironment across different cancer subtypes and identified spatial gradient-expressed genes related to epithelial–mesenchymal transition with the potential to predict tumor prognosis and progression. A spatial transcriptomics method achieves high gene detection sensitivity and flexible resolution. [ABSTRACT FROM AUTHOR]

Anomalous thermal expansion, or other words, negative thermal expansion (NTE), resulting from the lattice contraction upon temperature increasing, has been an enduring topic for material science and engineering. The variation of a lattice go with the temperature is straightly originated from its electronic structures and is inseparable from those physical properties. In the past several decades, many efforts have been made to searching new series of NTE compounds or control the thermal expansion performance in order to supply various demands of different extreme applications. These development of new NTE systems also dependences on the theoretical studies. Here, we carried out theoretical calculation on CrB2 and FeZr2 with anisotropic negative thermal expansion. Intriguingly, theoretical calculations reveal that the binding of either Cr-Cr pair or Fe-Fe pair is relatively small. The results reveal that the origin of NTE is the ordered magnetic state during the increasing of temperature. The localized electrons would prevent the lattice parameters increase with heating, which shows macroscopic NTE phenomenon. [ABSTRACT FROM AUTHOR]

For the purpose of improving the forming quality of cold extrusion internal thread and investigating the interactive effects of distinct process parameters on the forming quality of internal thread, this article established a regression response model between the influencing factors and optimization objectives by using the response surface experiment analysis method, and obtained the interactive effects of the bottom hole diameter, the extrusion speed and the coefficient of friction on the extrusion torque, extrusion temperature, and tooth height rate. The objective function was optimized using the regression model to obtain the optimal combination of parameters (bottom hole diameter 7.34 mm, extrusion speed 30 r/min, and friction coefficient 0.11). For the purpose of verifying the feasibility and validity of the theoretical model and the optimized design, internal thread extrusion experiments are carried out under the optimal combination parameters. The experiment results show that the extrusion torque is 3.17 N m, the extrusion temperature is 79.8 °C, and the tooth height rate is 77.23%, and the error with the predicted value is 8.56%, 2.57%, and 5.27%, respectively, which further demonstrates the accuracy of the model. [ABSTRACT FROM AUTHOR]

Mammalian hair cells (HCs) are arranged spirally along the cochlear axis and correspond to different frequency ranges. Serving as primary sound detectors, HCs spatially segregate component frequencies into a topographical map. HCs display significant diversity in anatomical and physiological characteristics, yet little is known about the organization of the cochleotopic map of HCs or the molecules involved in this process. Using single-cell RNA sequencing, we determined the distinct molecular profiles of inner hair cells and outer hair cells, and we identified numerous position-dependent genes that were expressed as gradients. Newly identified genes such as Ptn, Rxra, and Nfe2l2 were found to be associated with tonotopy. We employed the SCENIC algorithm to predict the transcription factors that potentially shape these tonotopic gradients. Furthermore, we confirmed that Nfe2l2, a tonotopy-related transcription factor, is critical in mice for sensing low-to-medium sound frequencies in vivo. the analysis of cell-cell communication revealed potential receptor-ligand networks linking inner hair cells to spiral ganglion neurons, including pathways such as BDNF-Ntrk and PTN-Scd4, which likely play essential roles in tonotopic maintenance. Overall, these findings suggest that molecular gradients serve as the organizing principle for maintaining the selection of sound frequencies by HCs. [ABSTRACT FROM AUTHOR]

Deep learning techniques, with their excellent feature extraction and representation, are being employed more and more in signal modulation recognition. However, most modulation identification systems lack transparency and are referred to as black boxes. The field has a restricted number of interpretable ways, and the currently available interpretable techniques lack considerable localization features. To address this issue, we present a method called Iterative Channel Relevance that enhances the Class Activation Mapping methodology(ICR-CAM). This proposed method is to provide a clearer understanding of how modulation recognition networks make judgments. By introducing the concept of channel scores, which assess the level of influence that shallow layers have on deep layers during the process of forward propagation. Coupled with the relevance score produced from backpropagation, this complicated score as the initial weight for every channel. Furthermore, drawing influence from the fundamentals of mask iterative optimization, This method provides for a thorough evaluation of channel significance in both the forward and backward directions, can create saliency map which strongly connect to the model's internal decision-making mechanism. Extensive investigations have revealed that ICR-CAM offers a more accurate visual localization capability compared to earlier approaches, as evidenced in both visual and quantitative assessments. [ABSTRACT FROM AUTHOR]

Coupled effects of biochar and antibiotic degrading bacterial strain on remediating contaminated soils with both heavy metals and antibiotics are poorly understood. A novel bio-based material combing an antibiotic degrading bacterial strain Herbaspirillum huttiense (HHS1) with biochar derived from spent mushroom substrate (BSMS) was developed, and an orthogonal test was conducted on soil contaminated with heavy metals and veterinary antibiotics. The stabilization of copper (Cu) and zinc (Zn) and the removal of oxytetracycline (OTC) and enrofloxacin (ENR) by the novel material at different temperatures were determined. Results indicated that the combination of BSMS and HHS1, along with temperature, was vital for pollutant treatments. The immobilized HHS1 (2 wt%)-BSMS (10 wt%) pellets achieved great stabilization efficiencies of Cu (69.2%) and Zn (59.72%), whereas higher removal of OTC (41.87%) and ENR (42.91%) was observed using HHS1 liquid and BSMS without entrapment at 35 ℃. The degradation of OTC and ENR by HHS1 accounted for 44.7% and 50.0% of their total removal, respectively. Oxytetracycline and ENR could be broken into small molecule products under low pH and high temperature through mechanisms including carbonylation, dihydroxylation, and piperazine ring-opening etc. When considering Cu and Zn stabilization, together with OTC and ENR removal in soils simultaneously, immobilized HHS1 (2 wt%)-BSMS (10 wt%) pellets are suitable for animal farms, even at low temperature (15 ℃), acting as an important bioresource for effectively stabilizing Cu and Zn and removing OTC and ENR in soil. [ABSTRACT FROM AUTHOR]

We demonstrate an all-fiber oscillator with high optical-to-optical efficiency using laser diodes working at 915nm as the pump sources to reduce the demand for thermal management. When the output power of the bidirectional pumped oscillator is 1.16kW, the optical-to-optical efficiency is as high as 75.4%. In this working state, the output characteristics of the oscillator are observed. The Raman suppression ratio is 41.23dB and the beam quality factor Mx2 = 1.14, My2 = 1.29. Analyzing the time trajectory of the highest power output, there are no significant characteristic peaks in the time domain signal and the frequency domain signal, which indicates that the oscillator has good stability.Improving the output characteristics of the 915nm pumping lasers has a positive significance for the application of non-strict ambient temperature control. [ABSTRACT FROM AUTHOR]

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Background: Phytoremediation is affected by physical and chemical properties of the soil such as soil pH, moisture, and nutrient content. Soil pH is a key element influencing Cd bioavailability and can be easily adjusted in agricultural practices. The soil pH level may relate to the effectiveness of phytoremediation; however, this has not been extensively investigated. In the current study, we evaluated the effect of Cd contamination level (0.56 and 0.92 mg/kg) and soil pH (5, 6, and 7) on Cd accumulation and allocation in Artemisia argyi, a fast-growing perennial crop. Results: Our results indicated that higher soil Cd concentrations reduce A. argyi biomass, and the loss of the root mass was particularly significant. Higher soil pH decreased Cd content in stems and roots of A. argyi cultivated in moderately Cd-polluted soil, and increased Cd content in stems and roots of the plant grown in low Cd-polluted soil. Higher soil pH decreased the percentage of Cd distributed in the soluble fraction and cell walls and increased the percentage of Cd in the organelles of leaf cells for moderate soil Cd levels. The bioconcentration and translocation factor exceeded 4.0 and 1.0, respectively, across all tested treatments, indicating that A. argyi is a promising candidate for phytoremediation. Notably, the effects of soil pH on Cd accumulation and subcellular distribution in A. argyi differed between low and moderately Cd-contaminated soils. Conclusion: Adjustments to soil pH based on the degree of Cd contamination can enhance Cd extraction by A. argyi, thereby reducing the overall remediation cycle of cadmium-polluted paddy fields of South China. [ABSTRACT FROM AUTHOR]

In order to improve the bioavailability of baicalin, this article prepared for α-zein loaded with baicalin composites (α-zein@BA) by pH driven method and they were characterized using scanning electron microscopy, infrared spectroscopy, and measurement of particle size distribution in water solution phase techniques. The digestive behavior and antioxidant activity of composites before and after simulating gastrointestinal fluid in vitro were studied as well. At the same time, molecular dynamics simulation techniques were used to reveal the molecular mechanism behind the formation of the composite between the two. The results indicated that the composites of α-zein@BA were observed to be approximately spherical under a scanning electron microscope, and their particle size was mainly distributed in the range of 94.55-145.10 μm in aqueous solution, whose encapsulation efficiency of baicalin was (86.61 ± 0.71) %. Infrared spectroscopy analysis indicated that α-zein and baicalin mainly formed complexes through hydrogen bonding, electrostatic and hydrophobic interactions. The measurement results of baicalin residue in simulated digestion of gastric and intestinal fluids in vitro are as follows: α-zein@BA > Baicalin, while both significantly increased in the gastric digestion stage (P < 0.05) and significantly decreased in the intestinal digestion stage (P < 0.05). Molecular dynamics simulation studies have shown that baicalin has a promoting effect on protein structural stability, and protein 158SER and GLN196 were mainly formed hydrogen bonds with it, while hydrophobic interactions were mainly manifested between non-polar amino acids such as PHE201 and PRO200. This study indicates that α-zein and baicalin can form stable composites, improving the bioavailability of baicalin. [ABSTRACT FROM AUTHOR]

The triglyceride glucose (TyG) related index, a metric used to evaluate assessing insulin resistance (IR), has received limited attention in its association with sarcopenia. Our study aims to explore the predictive potential of the TyG index for sarcopenia. This study utilized data from the China Health and Retirement Longitudinal Study, a nationally representative, community-based cohort study, including a sample size of 10,537 participants aged 45 years and older. Associations between TyG related index and sacopenia was explored using multivariate logistic regression. Analysis of the predictive value of TyG related index for sarcopenia using receiver-operating characteristic curve (ROC). We evaluated the correlation between the TyG related index and the risk of sarcopenia using Cox proportional hazards models. Additionally, we utilized restricted cubic spline (RCS) regression analyses to explore the connections between the TyG-related index and sarcopenia. Logistic regression analysis showed an association between TyG (OR 0.961[0.955,0.968], P < 0.001), TyG-body mass index (TyG-BMI) (OR 0.872[0.867,0.878], P < 0.001), TyG- waist circumference (TyG-WC) (OR 0.896[0.890,0.902], P < 0.001) and sarcopenia. The results of the ROC analysis indicated that the area under the curve values for TyG, TyG-BMI, and TyG-WC were 0.659, 0.903, and 0.819, respectively. Compared to those without sarcopenia, patients with sarcopenia had a 37.7% (HR 0.623[0.502,0.774], P < 0.001), 4.8% (HR 0.952[0.947,0.958], P < 0.001), and 0.4% (HR 0.996[0.995,0.996], P < 0.001) lower risk with increasing TyG, TyG-BMI, and TyG-WC, respectively. RCS results show nonlinear relationship between TyG-BMI (P < 0.001) and TyG-WC (P < 0.001) and risk of sarcopenia. We observed a correlation between the TyG-related index and sarcopenia, with the TyG-BMI index demonstrating strong predictive capability for sarcopenia. [ABSTRACT FROM AUTHOR]

The design of the reactant gas flow field structure in bipolar plates significantly influences the performance of proton exchange membrane fuel cells (PEMFCs). In this study, we introduced four innovative U-shaped flow field designs, namely: In-Out Multi-U, Out-In Multi-U, Distro In-Out Multi-U, and Distro Out-In Multi-U. To investigate the impact of these various flow fields on PEMFC performance, we conducted computational fluid dynamics (CFD) numerical simulations, validated through model experiments. Our results indicate that the Distro Out-In Multi-U flow field offers notable advantages compared to the conventional parallel flow field (CPFF) and conventional serpentine flow field (CSFF). These benefits include reduced inlet and outlet pressures, lower liquid water content, more uniform liquid water distribution, and a more even current density distribution. Furthermore, the Distro Out-In Multi-U design demonstrates improved efficiency, consuming less H2 (91.9%) than the CSFF while achieving a higher net power density output (10.1%). As a result, for the same power output, the Distro Out-In Multi-U utilizes only 83.5% of the H2 consumed by the CSFF. In summary, the U-shaped structured flow field exhibits superior output performance, enhanced energy efficiency, and improved resistance to flooding. These findings suggest that the U-shaped flow field design holds significant potential as a reactive flow field for PEMFCs. [ABSTRACT FROM AUTHOR]

The design of the reactant gas flow field structure in bipolar plates significantly influences the performance of proton exchange membrane fuel cells (PEMFCs). In this study, we introduced four innovative U-shaped flow field designs, namely: In-Out Multi-U, Out-In Multi-U, Distro In-Out Multi-U, and Distro Out-In Multi-U. To investigate the impact of these various flow fields on PEMFC performance, we conducted computational fluid dynamics (CFD) numerical simulations, validated through model experiments. Our results indicate that the Distro Out-In Multi-U flow field offers notable advantages compared to the conventional parallel flow field (CPFF) and conventional serpentine flow field (CSFF). These benefits include reduced inlet and outlet pressures, lower liquid water content, more uniform liquid water distribution, and a more even current density distribution. Furthermore, the Distro Out-In Multi-U design demonstrates improved efficiency, consuming less H2 (91.9%) than the CSFF while achieving a higher net power density output (10.1%). As a result, for the same power output, the Distro Out-In Multi-U utilizes only 83.5% of the H2 consumed by the CSFF. In summary, the U-shaped structured flow field exhibits superior output performance, enhanced energy efficiency, and improved resistance to flooding. These findings suggest that the U-shaped flow field design holds significant potential as a reactive flow field for PEMFCs. [ABSTRACT FROM AUTHOR]

The design of the reactant gas flow field structure in bipolar plates significantly influences the performance of proton exchange membrane fuel cells (PEMFCs). In this study, we introduced four innovative U-shaped flow field designs, namely: In-Out Multi-U, Out-In Multi-U, Distro In-Out Multi-U, and Distro Out-In Multi-U. To investigate the impact of these various flow fields on PEMFC performance, we conducted computational fluid dynamics (CFD) numerical simulations, validated through model experiments. Our results indicate that the Distro Out-In Multi-U flow field offers notable advantages compared to the conventional parallel flow field (CPFF) and conventional serpentine flow field (CSFF). These benefits include reduced inlet and outlet pressures, lower liquid water content, more uniform liquid water distribution, and a more even current density distribution. Furthermore, the Distro Out-In Multi-U design demonstrates improved efficiency, consuming less H2 (91.9%) than the CSFF while achieving a higher net power density output (10.1%). As a result, for the same power output, the Distro Out-In Multi-U utilizes only 83.5% of the H2 consumed by the CSFF. In summary, the U-shaped structured flow field exhibits superior output performance, enhanced energy efficiency, and improved resistance to flooding. These findings suggest that the U-shaped flow field design holds significant potential as a reactive flow field for PEMFCs. [ABSTRACT FROM AUTHOR]

Elastomers with high strength and toughness, excellent self-healing properties, and biocompatibility have broad application prospects in wearable electronics and other fields, but preparing it remains a challenge. In this work, we propose a highly adaptable strategy by introducing the small molecule crosslinking agent of triethanolamine (TEA) to the poly thioctic acid (PTA) chains and preparing the PAxEy elastomers using a simple synthesis step. This strategy stabilizes the PTA chains by constructing multiple non-covalent cross-linked dynamic networks, endowing materials with excellent strength and toughness (tensile strength of 288 kPa, toughness of 278.2 kJ/m3), admirable self-healing properties (self-healing efficiency of 121.6% within 7 h at 70 °C), and good biocompatibility. The PAxEy elastomers can also be combined with MWNTs to become flexible strain sensors, which can be used to monitor human joint movements with high sensitivity, repeatable responses, and stability. [ABSTRACT FROM AUTHOR]

The consensus reaching process (CRP) is often utilized to mitigate conflicts among decision makers and help them reach an agreement. Almost all existing CRP models focused on obtaining a consensual complete ranking of alternatives. However, in many situations, it may be sufficient to classify alternatives into a number of ordinal classes rather than a complete ranking. To this end, this study proposes an ordinal classification-based CRP (OCCRP) with the aim to generate consensual ordinal classes of alternatives. Further, this study investigates the OCCRP in the large-scale multi-attribute group decision making context, in which flexible linguistic expression is used to model uncertain opinions of decision makers. In the OCCRP, an approach is proposed to manage flexible linguistic expression by transforming it into linguistic distribution assessment. Then, an opinion clustering and aggregation approach is used to deal with the assessment information of the large group. Next, an approach-based technique for order performance by similarity to ideal solution is used to obtain the ordinal classification of alternatives. Following this, a feedback adjustment mechanism is presented to help decision makers improve their consensus level on the ordinal classification of alternatives. Finally, a numerical example about grape wine grading problem and a comparative analysis are presented to demonstrate the validity of the proposal. [ABSTRACT FROM AUTHOR]

Background: Liver cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in hepatocellular carcinoma (HCC). The Wnt/β-catenin pathway plays a crucial role in liver cancer stemness, progression, metastasis, and drug resistance, but no clinically approved drugs have targeted this pathway efficiently so far. We aimed to elucidate the role of COLEC10 in HCC stemness. Methods: The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were employed to search for the association between COLEC10 expression and HCC stemness. Colony formation, sphere formation, side population, and limiting dilution tumor initiation assays were used to identify the regulatory role of COLEC10 overexpression in the stemness of HCC cell lines. Wnt/β-catenin reporter assay and immunoprecipitation were performed to explore the underlying mechanism. Results: COLEC10 level was negatively correlated with HCC stemness. Elevated COLEC10 led to decreased expressions of EpCAM and AFP (alpha-fetoprotein), two common markers of liver CSCs. Overexpression of COLEC10 inhibited HCC cells from forming colonies and spheres, and reduced the side population numbers in vitro, as well as the tumorigenic capacity in vivo. Mechanically, we demonstrated that overexpression of COLEC10 suppressed the activity of Wnt/β-catenin signaling by upregulating Wnt inhibitory factor WIF1 and reducing the level of cytoplasmic β-catenin. COLEC10 overexpression promoted the interaction of β-catenin with the component of destruction complex CK1α. In addition, KLHL22 (Kelch Like Family Member 22), a reported E3 ligase adaptor predicted to interact with CK1α, could facilitate COLEC10 monoubiquitination and degradation. Conclusion: COLEC10 inhibits HCC stemness by downregulating the Wnt/β-catenin pathway, which is a promising target for liver CSC therapy. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32–55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26–58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133. [ABSTRACT FROM AUTHOR]

Objectives: To explore the value of the synthetic MRI (SyMRI), combined with amide proton transfer–weighted (APTw) MRI for quantitative and morphologic assessment of sinonasal lesions, which could provide relative scale for the quantitative assessment of tissue properties. Methods: A total of 80 patients (31 malignant and 49 benign) with sinonasal lesions, who underwent the SyMRI and APTw examination, were retrospectively analyzed. Quantitative parameters (T1, T2, proton density (PD)) and APT % were obtained through outlining the region of interest (ROI) and comparing the two groups utilizing independent Student t test or a Wilcoxon test. Receiver operating characteristic curve (ROC), Delong test, and logistic regression analysis were performed to assess the diagnostic efficiency of one-parameter and multiparametric models. Results: SyMRI-derived mean T1, T2, and PD were significantly higher and APT % was relatively lower in benign compared to malignant sinonasal lesions (p < 0.05). The ROC analysis showed that the AUCs of the SyMRI-derived quantitative (T1, T2, PD) values and APT % ranged from 0.677 to 0.781 for differential diagnosis between benign and malignant sinonasal lesions. The T2 values showed the best diagnostic performance among all single parameters for differentiating these two masses. The AUCs of combined SyMRI-derived multiple parameters with APT % (AUC = 0.866) were the highest than that of any single parameter, which was significantly improved (p < 0.05). Conclusion: The combination of SyMRI and APTw imaging has the potential to reflect intrinsic tissue characteristics useful for differentiating benign from malignant sinonasal lesions. Clinical relevance statement: Combining synthetic MRI with amide proton transfer–weighted imaging could function as a quantitative and contrast-free approach, significantly enhancing the differentiation of benign and malignant sinonasal lesions and overcoming the limitations associated with the superficial nature of endoscopic nasal sampling. Key Points: • Synthetic MRI and amide proton transfer–weighted MRI could differentiate benign from malignant sinonasal lesions based on quantitative parameters. • The diagnostic efficiency could be significantly improved through synthetic MRI + amide proton transfer–weighted imaging. • The combination of synthetic MRI and amide proton transfer–weighted MRI is a noninvasive method to evaluate sinonasal lesions. [ABSTRACT FROM AUTHOR]

The expression of aflD gene plays a significant role in the biosynthesis of aflatoxin, aflD structural genes can be served as a good biomarker of aflatoxigenic strains. The detection of the aflD gene is a promising method to control the further spread of aflatoxins. In this research, a rapid fluorescence biosensor targeting aflatoxigenic biosynthesis-related genes aflD was developed based on nitrogen-doped carbon quantum dots (NCQDs) and AuNPs as fluorescence donors and quenchers respectively. This sensor was fabricated by immobilization of NCQDs and AuNPs on the two ends of hairpin DNA. In the absence of the aflD gene, NCQDs were closed to AuNPs to trigger the fluorescence resonance energy transfer leading to a quenching and showed the fluorescent signal "off". In the presence of the aflD gene, NCQDs and AuNPs were separated by the target aflD gene complementary matching with the loop of the hairpin structure, which caused to the recovery of fluorescence signal and performance the fluorescent signal "on". It was shown that the biosensor provided an excellent limit of detection (LOD) of 1.95 nM (3σ / k) with a liner range of 10–150 nM. Besides, this biosensor performed the satisfied selectivity through the comparison between aflD gene and mismatched DNA sequences. The feasibility of this biosensor was examined in rice contaminated by Aspergillus flavus. Therefore, it could potentially be used as a feasible tool for preventing aflatoxin in grain and its products. [ABSTRACT FROM AUTHOR]

Interface is the focus of composite material research. The interfacial structure of composites is affected by many factors, including particle size, additional elements, and preparation technology. This paper aims to investigate how heat affects the interfacial microstructure and mechanical properties of tungsten carbide particle-reinforced steel matrix composites. In this study, tungsten carbide particles were sealed as porous preforms, and the composites were prepared by casting infiltration method, with molten high-chromium steel filling the preforms. The heat gain of the composite gradually decreased in the infiltration direction from the substrate to the composite surface. The interfacial microstructure and properties of the composites were characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, microhardness test and three-point bending fatigue test. The results revealed that the α-W2C phase decomposed before the h-WC phase, and the M3W3C carbide increased with the dissolution of tungsten carbide particles. α-W2C and h-WC were completely decomposed in the high-heating joint surface area, and the interface boundary is clearly visible. With the decrease in heat, h-WC could not be completely decomposed, and a large number of gray rod-like phases of h-WC appeared in the interface. The bonding strength of the composite gradually decreased, and the average Vickers hardness of the interface decreased from 1376 to 855 HV while plasticity increased. [ABSTRACT FROM AUTHOR]

In order to fulfill the urgent requirements of functional products, circuit integration of different functional devices are commonly utilized. Thus, issues including production cycle, cost, and circuit crosstalk will get serious. Neuromorphic computing aims to break through the bottle neck of von Neumann architectures. Electronic devices with multi-operation modes, especially neuromorphic devices with multi-mode cognitive activities, would provide interesting solutions. Here, pectin/chitosan hybrid electrolyte gated oxide neuromorphic transistor was fabricated. With extremely strong proton related interfacial electric-double-layer coupling, the device can operate at low voltage of below 1 V. The device can also operate at multi-operation mode, including bottom gate mode, coplanar gate and pseudo-diode mode. Interestingly, the artificial synapse can work at low voltage of only 1 mV, exhibiting extremely low energy consumption of ∼7.8 fJ, good signal-to-noise ratio of ∼229.6 and sensitivity of ∼23.6 dB. Both inhibitory and excitatory synaptic responses were mimicked on the pseudo-diode, demonstrating spike rate dependent plasticity activities. Remarkably, a linear classifier is proposed on the oxide neuromorphic transistor under synaptic metaplasticity mechanism. These results suggest great potentials of the oxide neuromorphic devices with multi-mode cognitive activities in neuromorphic platform. [ABSTRACT FROM AUTHOR]

Chlorophenol wastewater has a serious impact on the environment, and it is not easily degraded by traditional methods. The novel electrochemical hydrogen evolution reduction degradation has received widespread attention, among which the electrocatalytic performance of the electrode is particularly critical. In this study, Pd-Fe2O3-coated nickel foam electrode (Pd-Fe2O3-Ni) was prepared by annealing on Fe–Ni and introducing Pd into Fe2O3. Its degradation performance is better than that of the original nickel foam (Ni) and Fe2O3-Ni electrodes. The removal of 4-chlorophenol by Pd-Fe2O3-Ni was 98.2%, which was 1.4–1.52, 10–12 and 10.3–11.4 times higher than that of the unannealed Pd-Fe2O3-Ni, Ni, and Fe2O3-Ni, respectively. Meanwhile, the Pd-Fe2O3-Ni electrode had good stability, and the 4-chlorophenol removal rate was maintained at 92% after five repetitions, which proved the applicability of the Pd-Fe2O3-Ni electrode. Therefore, the prepared Pd-Fe2O3-Ni is a high-performance electrode for electrochemical reduction and degradation of wastewater. [ABSTRACT FROM AUTHOR]

Highlights: Comprehensively reviewed the progress in research on graphene electrode-based triboelectric nanogenerators (TENGs) from two dimensions, including precision processing methods of graphene electrodes and applications of TENGs. Discussed the various applications of graphene electrode-based TENGs in different scenarios, as well as the ways in which graphene electrodes enhance the performance of TENGs. Offered a prospective discussion on the future development of graphene electrode-based TENGs, with the aim of promoting continuous advancements in this field. With the continuous development of wearable electronics, wireless sensor networks and other micro-electronic devices, there is an increasingly urgent need for miniature, flexible and efficient nanopower generation technology. Triboelectric nanogenerator (TENG) technology can convert small mechanical energy into electricity, which is expected to address this problem. As the core component of TENG, the choice of electrode materials significantly affects its performance. Traditional metal electrode materials often suffer from problems such as durability, which limits the further application of TENG. Graphene, as a novel electrode material, shows excellent prospects for application in TENG owing to its unique structure and excellent electrical properties. This review systematically summarizes the recent research progress and application prospects of TENGs based on graphene electrodes. Various precision processing methods of graphene electrodes are introduced, and the applications of graphene electrode-based TENGs in various scenarios as well as the enhancement of graphene electrodes for TENG performance are discussed. In addition, the future development of graphene electrode-based TENGs is also prospectively discussed, aiming to promote the continuous advancement of graphene electrode-based TENGs. [ABSTRACT FROM AUTHOR]

Background: The potential effects of global warming on soil fungal communities and their functions remain uncertain. To address this issue, we investigated the effects of 3-year simulated field warming on the community and function of fungi in a temperate steppe of Inner Mongolia, northern China. Methods: The diversity and structure of the fungal community were measured by high-throughput sequencing. The functionality of fungal communities was identified by comparison with the ITS reference database. Results: Our results showed that warming did not affect the diversity of fungi, but significantly increased the complexity of the fungal community, with fungal taxa more closely associating with each other. We observed that plant pathogens and arbuscular mycorrhizal fungi were the most abundant functional groups. Meanwhile, warming significantly decreased the relative abundance of animal pathogens. Conclusions: Warming significantly increased the complexity of the fungal community, with soil pH being the main factor affecting soil fungal function. Our findings emphasize that the response of the fungal community and its functional groups to warming has significant implications for ecosystem biogeochemical cycling. [ABSTRACT FROM AUTHOR]

Boron-doped biochar (B-BC) was synthesized by pyrolysis using solid waste of sorghum straw as raw material. The specific surface area of B-BC increased significantly by 2.38 times compared to that of pure BC. This enhancement allowed B-BC (0.3 g L−1) to achieve complete adsorption of 10 mg L−1 tartrazine (TTZ) within 40 min. Moreover, acidic conditions were more favorable for TTZ adsorption, achieving complete removal of TTZ in only 15 min at a pH of 3.0. Interestingly, the adsorption rate of TTZ by B-BC in the presence of 0.05 M Cl− was approximately 2.12 times higher than that in the absence of Cl−. When other background electrolytes were present, excluding PO43−, complete adsorption of TTZ could also be achieved within 60 min. Thermodynamic analysis and DFT calculations described the parameters of B-BC for TTZ adsorption, including Δ G Θ (< 0 kJ mol−1), Δ H Θ (− 2.199 kJ mol−1), Δ S Θ (− 6.068 J mol−1 K−1), and the adsorption energy (Eads = − 0.6919 eV), indicating a tendency towards a spontaneous adsorption process. Moreover, the strong electron transfer ability of B-BC and the oxygen-containing groups promoted the activation of PDS and generation of active substances such as 1O2, O2•−, and SO4•−, thereby degrading TTZ into products with lower biological toxicity. When the added PDS was only 0.1 mM, the degradation rate constant of TTZ could reach 0.1481 min−1. Furthermore, boron doping enhanced the stability of biochar, enabling the complete removal of 10 mg L−1 TTZ even after recycling and regeneration. In summary, this study offers a practical solution for the resource utilization of solid waste sorghum straw and the treatment of TTZ-polluted wastewater. Highlights: Boron doping significantly increased the specific surface area of biochar by 2.38 times. B-BC exhibited complete adsorption of TTZ in only 15 min at a pH of 3.0. Addition of 0.05 M Cl− increased the adsorption rate of TTZ on B-BC by 1.12 times. Free radicals and nonradicals contributed to TTZ degradation in B-BC/PDS system. Degradation products of TTZ displayed reduced toxicity to typical aquatic organisms. [ABSTRACT FROM AUTHOR]

Allosteric drugs offer a new avenue for modern drug design. However, the identification of cryptic allosteric sites presents a formidable challenge. Following the allostery nature of residue-driven conformation transition, we propose a state-of-the-art computational pipeline by developing a residue-intuitive hybrid machine learning (RHML) model coupled with molecular dynamics (MD) simulation, through which we can efficiently identify the allosteric site and allosteric modulator as well as reveal their regulation mechanism. For the clinical target β2-adrenoceptor (β2AR), we discover an additional allosteric site located around residues D792.50, F2826.44, N3187.45 and S3197.46 and one putative allosteric modulator ZINC5042. Using Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and protein structure network (PSN), the allosteric potency and regulation mechanism are probed to further improve identification accuracy. Benefiting from sufficient computational evidence, the experimental assays then validate our predicted allosteric site, negative allosteric potency and regulation pathway, showcasing the effectiveness of the identification pipeline in practice. We expect that it will be applicable to other target proteins. The identification of cryptic allosteric sites presents a formidable challenge. Here, the authors develop a residue-intuitive hybrid ML model coupled with MD simulation to successfully identify a novel allosteric site of β2AR and a negative allosteric modulator. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an effective chemotherapeutic drug, but its use can lead to cardiomyopathy, which is the leading cause of mortality among cancer patients. Macrophages play a role in DOX-induced cardiomyopathy (DCM), but the mechanisms undlerlying this relationship remain unclear. This study aimed to investigate how IKKα regulates macrophage activation and contributes to DCM in a mouse model. Specifically, the role of macrophage IKKα was evaluated in macrophage-specific IKKα knockout mice that received DOX injections. The findings revealed increased expression of IKKα in heart tissues after DOX administration. In mice lacking macrophage IKKα, myocardial injury, ventricular remodeling, inflammation, and proinflammatory macrophage activation worsened in response to DOX administration. Bone marrow transplant studies confirmed that IKKα deficiency exacerbated cardiac dysfunction. Macrophage IKKα knockout also led to mitochondrial damage and metabolic dysfunction in macrophages, thereby resulting in increased cardiomyocyte injury and oxidative stress. Single-cell sequencing analysis revealed that IKKα directly binds to STAT3, leading to the activation of STAT3 phosphorylation at S727. Interestingly, the inhibition of STAT3-S727 phosphorylation suppressed both DCM and cardiomyocyte injury. In conclusion, the IKKα-STAT3-S727 signaling pathway was found to play a crucial role in DOX-induced cardiomyopathy. Targeting this pathway could be a promising therapeutic strategy for treating DOX-related heart failure. [ABSTRACT FROM AUTHOR]

Background and aims: Enhanced silicate rock weathering (ERW) on cropland soils can increase crop yield and promote carbon dioxide (CO2) sequestration. Applying silicate rock powder to flooded rice paddies can promote weathering, but the effects of ERW on rice production and CO2 removal rates in the field remain unclear. Methods: We investigated the effects of adding wollastonite (CaSiO3) powder (5 t ha−1) to rice paddy plots on soil properties, rice yield, rice grain quality, grain arsenic, grain cadmium, and soil CO2 sequestration in Liaoning Province, Northeast China. Results: Wollastonite application increased soil pH, soil available silicon (Si) content, and Si uptake by rice. Wollastonite application increased grain number by 10% per panicle (15 ± 2), total grain number by 15%, and rice yield by 12% (1.4 ± 0.1 t ha−1). After five months of rice growth, soil inorganic carbon (SIC) content in the surface soil increased by 1.20 ± 0.03 t CO2 ha−1 in wollastonite treatments. We estimated a net profit of $300 (U.S.) ha−1 from yield increase and carbon trade with wollastonite application to this paddy field. Conclusions: Wollastonite application to paddy fields in Northeast China promoted rice yield and CO2 sequestration in the surface soil. This soil CO2 sequestration triples that from the control soil and is comparable to prior pot trials. Although field trials are needed on the limits to CO2 sequestration and rice yield increases with wollastonite application, such applications promise to increase soil CO2 sequestration and profits for a key crop. [ABSTRACT FROM AUTHOR]

Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA. [ABSTRACT FROM AUTHOR]

Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA. [ABSTRACT FROM AUTHOR]

A finite element model of cervical kyphosis was established to analyze the stress of cervical spine under suspensory traction and to explore the mechanism and effect of it. A patient with typical cervical kyphosis (C2-C5) underwent CT scan imaging, and 3D slicer was used to reconstruct the C2 to T2 vertebral bodies. The reconstructed data was imported into Hypermesh 2020 and Abaqus 2017 for meshing and finite element analysis. The changes of the kyphotic angle and the von Mises stress on the annulus fibrosus of each intervertebral disc and ligaments were analyzed under suspensory traction conditions. With the increase of suspensory traction weight, the overall kyphosis of cervical spine showed a decreasing trend. The correction of kyphosis was mainly contributed by the change of kyphotic segments. The kyphotic angle of C2-C5 was corrected from 45° to 13° finally. In cervical intervertebral discs, the stress was concentrated to anterior and posterior part, except for C4-5. The stress of the anterior longitudinal ligament (ALL) decreased from the rostral to the caudal, and the high level von Mises stress of the kyphotic segments appeared at C2-C3, C3-C4, and C4-C5. The roles of the other ligaments were not obvious. The kyphotic angle was significantly reduced by the suspensory traction. Shear effect due to the high von Mises stress in the anterior and posterior parts of annulus fibrosus and the tension on the anterior longitudinal ligament play a role in the correction of cervical kyphosis. [ABSTRACT FROM AUTHOR]

Objective: We intended to map the single-cell profile of OLP, explore the molecular characteristics of unconventional T cells in OLP tissues. Methods: Buccal mucosa samples from OLP patients and healthy individuals were used to prepare single-cell suspension. Single-cell RNA sequencing was used to analyze the proportion of all the cells, and the molecular characteristics of unconventional T cells. Immunohistochemical staining was used to detect the expression of unconventional T cells marker genes. Results: The cell clusters from buccal mucosa were categorized into immune cells, fibroblasts, endothelial cells, and epithelial cells. Unconventional T cells with phenotype of CD247+TRDC+NCAM1+ were identified. Immunohistochemical staining revealed higher expression of unconventional T cell marker genes in OLP tissue, predominantly in the lamina propria. In OLP, unconventional T cells are in a unique stress response state, exhibited enhanced NF-κB signaling and apoptosis inhibition, enhanced heat shock protein genes expression, weakened cytotoxic function. A large number of ligand-receptor pairs were found between unconventional T cells and other cells, particularly with fibroblasts and endothelial cells. Conclusions: This study mapped the single-cell profile of OLP, delineated the molecular characteristics of unconventional T cells in OLP, and uncovered that these unconventional T cells are in a stress response state. [ABSTRACT FROM AUTHOR]

Asymmetric tidal dynamics are of great significance for material transport and morphological evolution in estuaries. The tidal dynamics of the macro-tidal Hangzhou Bay (HZB) are characterized by flood-ebb asymmetries, spring-neap asymmetries, surface-bottom asymmetries, and up-downstream asymmetries. The mechanisms of spatio-temporal asymmetric tides and lateral flows in HZB were studied through a fully calibrated three-dimensional numerical model. The results show that tidal tides, tidal currents, and tidal asymmetry in HZB varied specially and temporally. In general, the bay was mostly flood-dominant. Temporally, tidal duration asymmetry in the bay fluctuated between spring and neap tides, with larger skewness during spring tides and smaller skewness during neap tides. The locally produced overtides are the primary sources of shallow-water tides in the bay, and the interaction between the lunar semi-diurnal tide M2 and the solar semi-diurnal tide S2 generates shallow-water overtides and deforms tidal asymmetries. The dissipated tidal energy may consumed by the bottom friction, with less passed to the generated shallow water overtides M4 and M6 tides (AM4 = 12.07 cm, AM6 = 3.91 cm) when comparing with the experiments that open boundary is purely forced by M2 tide (AM4 = 13.63 cm, AM6 = 6.31 cm). The increased depth reduces the bottom friction and the convergence of volume, resulting in skewness values close to zero (γTDA = 0.220, γM2-M4 = 0.141, γM2-M4-M6 = −0.002, γM2-S2-MS4 = 0.105). The changes of tidal duration asymmetry caused by the increased channel convergence, reduced bay width, and reclaimed intertidal zone spatially vary in different parts. The bottom friction contributed to the generation of the shallow-water tides and asymmetries in the bay (the RVRs for M4 and M6 are −73.5% and −92.5%), while the Coriolis force (the RVRs for M4 and M6 are 4.8% and 8.9%) and nonlinear advection (the RVRs for M4 and M6 are −17.3% and − 21.8%) are minor factors. The findings of the study provide hydrodynamic foundations for the research of sediment transport and estuarine evolution in similar macro-tidal turbid estuaries worldwide. [ABSTRACT FROM AUTHOR]

Fecal sterols are traditionally ascribed as important biomarkers for animal excrement, and have been widely used to identify the source of organic matter and to reconstruct paleoecological changes in Antarctic terrestrial, aquatic, and marine ecosystems. However, the in situ microbial hydrogenation of cholesterol to coprostanol could have significance as a proxy to infer paleoenvironmental studies in Antarctica, particularly in anoxic sediment. Here, we report that abundant coprostanol, which was traditionally deemed as a biomarker for human sewage contamination, was found in three anoxic sediment profiles (AC2, BI, and CH1), which were strongly influenced by animal excrement at North Victoria Land, western Ross Sea, Antarctica. Our results suggest that the high concentrations of coprostanol in these three sediment profiles were not due to animal excrement, since coprostanol is not present in penguin guano and is a minor component in seal excrement. Coprostanol/cholesterol and coprostanol/(coprostanol + cholestanol) ratios suggest that coprostanol in the sediment cores of AC2 and BI was primarily derived from bacterial hydrogenation of cholesterol introduced by penguin guano. Coprostanol in CH1 sediments is related to human sewage due to intensive research activities from 1968 to 2006 in this region. However, the low abundance of coprostanol and the ratios of coprostanol/cholesterol and coprostanol/(coprostanol + cholestanol) in a relatively oxidizing sediment core (IIL1) infer that coprostanol was likely contributed by seal settlement. Together with high-throughput sequencing of the 16S rRNA gene, the conversion of cholesterol to coprostanol by anaerobic bacteria (e.g., Eubacterium coprostanoligenes) could occur in anoxic aquatic systems. Our results suggest that the presence of coprostanol in Antarctic lacustrine sediment with anoxic conditions does not necessarily indicate seal activity and human waste as the microbial hydrogenation of cholesterol to coprostanol should also be considered. [ABSTRACT FROM AUTHOR]