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Abstract In this study, the removal effect of a new MOF-on MOF adsorbent based on Cu–Co bimetallic organic frameworks on tetracycline antibiotics (TCs) in water system was studied. The adsorbent (Cu-MOF@Co-MOF) were synthesized by solvothermal and self-assembly method at different concentrations of Co2+/Cu2+. The characterization results of SEM, XRD, XPS, FTIR and BET indicated that the MOF-on MOF structure of Cu-MOF@Co-MOF exhibited the best recombination and physicochemical properties when the molar ratio of Co2+: Cu2+ is 5:1. In addition, the Cu-MOF@Co-MOF have a high specific surface area and bimetallic clusters, which can achieve multi-target synergistic adsorption of TCs. Based on above advantages, Cu-MOF@Co-MOF provided a strong affinity and could efficiently adsorb more than 80% of pollutants in just 5 to 15 min using only 10 mg of the adsorbent. The adsorption capacity of tetracycline and doxycycline was 434.78 and 476.19 mg/g, respectively, showing satisfactory adsorption performance. The fitting results of the experimental data were more consistent with the Langmuir isotherm model and pseudo-second-order kinetic model, indicating that the adsorption process of TC and DOX occurred at the homogeneous adsorption site and was mainly controlled by chemisorption. Thermodynamic experiments showed that Cu-MOF@Co-MOF was thermodynamically advantageous for the removal of TCs, and the whole process was spontaneous. The excellent adsorption capacity and rapid adsorption kinetics indicate the prepared MOF-on MOF adsorbent can adsorb TCs economically and quickly, and have satisfactory application prospects for removing TCs in practical environments. The results of the study pave a new way for preparing novel MOFs-based water treatment materials with great potential for efficient removal.

Abstract Aiming at the problem of "crystallization" on the surface of Yuan blue and white ceramics, which causes reflections and loss of image texture, an image processing method is proposed to repair the image texture information. A multi-scale Retinex pre-processing method is proposed to enhance the contrast between the pattern and the background. A color factor is introduced to prevent color distortion. A weighted average function is constructed to enhance image details and improve texture information. The Yuan blue and white pattern can be effectively segmented from the background using a combination of multi-peak thresholding for segmentation and other techniques. The experimental results demonstrate that, in comparison to other algorithms, the multi-scale Retinex and histogram multi-peak threshold coupled segmentation method proposed in this paper exhibits the highest F1-score of 0.03067 and an accuracy of 92.67% in cross-evaluation with other algorithms. This indicates that the overall performance of the algorithm is the best. The proposed method has the potential to inform the protection of cultural relics.

Abstract Background Tall wheatgrass is a perennial salt‐tolerant bunchgrass, which is a promising candidate for establishing a “Coastal Grass Belt” in China, particularly in the coastal saline–alkaline soils surrounding the Bohai Sea. Methods Seven harvesting treatments were performed to explore the optimal harvesting time and frequency for tall wheatgrass in coastal area. The dry matter yield (DMY) and forage nutritional values were investigated for each cut. The correlation between harvesting time and frequency thereof among the investigated traits was also determined. Results The results showed that the two‐cut on June 18 and October 29 produced the highest DMY. Another two‐cut on May 26 and October 29 produced a relatively high crude protein (CP) yield. The DMY, contents of neutral detergent fiber (NDF), acid detergent fiber (ADF), and crude cellulose (CC) as well as CP yield were positively correlated to plant height, while the CP content and the relative feed value (RFV) were negatively correlated to plant height. The accumulating growing degree days, accumulated precipitation, and sunshine duration were positively correlated with plant height, DMY, contents of NDF, ADF, and CC as well as CP yield, but negatively correlated with CP content and RFV for the first cut. Conclusions The two‐cut treatment at the end of May and October may be suitable for tall wheatgrass in the “Coastal Grass Belt” targeted area.

Abstract Background Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self‐renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non‐small cell lung cancer (NSCLC) remains unclear. Methods The proportion of ALDHhi cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit β‐catenin while pcDNA3‐β‐catenin (S33Y) plasmid enhanced the expression of β‐catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real‐time PCR. Results We found that hypoxia led to an increase in the proportion of ALDHhi cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDHhi cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, β‐catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDHhi cells in both cell lines was decreased by β‐catenin inhibitor or siRNA knockdown, whereas increased after β‐catenin overexpression. Furthermore, hypoxia treatment suppressed E‐cadherin expression in H520 cells and enhanced N‐cadherin and β‐catenin expression, while this effect was completely opposite in A549 cells. Conclusion The hypoxia‐EMT‐β‐catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future.

Abstract Backgrounds Microfibril-associated protein 2 (MFAP2) is a protein presenting in the extracellular matrix that governs the activity of microfibrils through its interaction with fibrillin. While the involvement of MFAP2 in metabolic disorders has been documented, its expression and prognostic significance in triple-negative breast cancer (TNBC) remain unexplored. Methods We acquired datasets pertaining to breast cancer (BC) from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Next, a Venn diagram was used to identify the differentially expressed genes (DEGs). The DEGs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), immune and survival analysis. The expressions of MFAP2, PD-1 and PD-L1 were examined by immunohistochemistry and western blot and their relationship with clinical pathological parameters were analyzed by clinical specimen samples from patients with TNBC. Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/ ) was adopted to calculate the immune infiltration level of TNBC. The link between gene expression and tumor mutational burden (TMB) was described using Spearman’s correlation analysis. Results We identified 66 differentially expressed genes (DEGs) that were up-regulated. Among these DEGs, MFAP2 was found to be overexpressed in TNBC and was associated with a lower probability of survival. This finding was confirmed through the use of immunohistochemistry and western blot techniques. Additionally, MFAP2 was found to be related to various pathological parameters in TNBC patients. Mechanistically, gene set enrichment analysis (GSEA) revealed that MFAP2 primarily influenced cellular biological behavior in terms of epithelial mesenchymal transition, glycolysis, and apical junction. Notably, MFAP2 expression was positively correlated with the abundance of macrophages, while a negative correlation was observed with the abundance of B cells, CD4 + T cells, CD8 + T cells, neutrophils and dendritic cells through immune analysis. Furthermore, it was observed that MFAP2 displayed a negative correlation not only with tumor mutational burden (TMB), a recognized biomarker for PD-1/PD-L1 immunotherapy, but also with PD-L1 in samples of TNBC. Conclusion MFAP2 may be an important prognostic biomarker for TNBC, as well as a viable target for immunotherapy in this disease.

We de novo assembled and analysed the chloroplast genomes of Capsella bursa-pastoris, Descurainia sophia, and Lepidium apetalum of the plant family Brassicaceae. These chloroplast genomes exhibited a quadripartite structure characterised by inverted repeat regions (26,268–26,460 bp) separating large single copy (83,771–83,870 bp) and small single copy (17,570–18,014 bp) regions. Genetic analysis revealed 112 unique genes, comprising 78 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. Notably, phylogenetic analysis of 21 species revealed close relationships between C. bursa-pastoris and C. orientalis, D. sophia and D. erodiifolia, and L. apetalum and L. cordatum, with 100% bootstrap support. In conclusion, the analysis of these genomes will contribute to the growing knowledge of chloroplast genomes in the Brassicaceae family and of the specific genera Capsella, Descurainia, and Lepidium.

Three-cycle minimum surface structures show excellent lightweight and energy absorption capabilities, and additive manufacturing techniques provide a unique degree of freedom for lattice structure design. Therefore, in this study, three-period minimum surface (TPMS) structures of Schwarz-P boron steel alloys were prepared by Selective Laser Melting (SLM) technique. By investigating the effect of lattice structure design, we have analyzed the deformation behavior, mechanical properties and energy absorption capacity under compression. In addition, tensile properties and fracture morphology were analyzed to gain insight into the performance characteristics of these structures, and the effect of structural design on hardness was explored. The results of the study show that the structural design has a small effect on the microstructure and hardness. Under compressive loading, the P (0.5 1) structure exhibits a uniform deformation behavior, while the other four structures show a crushing deformation pattern. In particular, the P (0.5 1) structure exhibits excellent compressive performance, with an energy absorption work per unit mass as high as 296.2 J/mm^3, and its stiffness reaches 1627 MPa. Meanwhile, the P (0.35 1) structure exhibits excellent tensile performance with the tensile strength of 687 MPa. The morphological analysis of the tensile fracture reveals that the fracture mainly occurs in the strut nodes, and it mainly exhibits ductile tensile fracture.

Highlights MXene/TiO2 hybrids are prepared by a simple calcination treatment, and their electromagnetic response is customized by in situ atomic reconstruction engineering. Based on the excellent electromagnetic response of MXene/TiO2 hybrids, a series of electromagnetic devices are constructed. Multi-spectrum stealth is realized covering visible-light, infrared radiation and GHz.

Abstract Atomically precise defect engineering is essential to manipulate the properties of emerging topological quantum materials for practical quantum applications. However, this remains challenging due to the obstacles in modifying the typically complex crystal lattice with atomic precision. Here, we report the atomically precise engineering of the vacancy-localized spin–orbit polarons in a kagome magnetic Weyl semimetal Co3Sn2S2, using scanning tunneling microscope. We achieve the step-by-step repair of the selected vacancies, leading to the formation of artificial sulfur vacancies with elaborate geometry. We find that that the bound states localized around these vacancies undergo a symmetry dependent energy shift towards Fermi level with increasing vacancy size. As the vacancy size increases, the localized magnetic moments of spin–orbit polarons become tunable and eventually become itinerantly negative due to spin–orbit coupling in the kagome flat band. These findings provide a platform for engineering atomic quantum states in topological quantum materials at the atomic scale.

Liver fibrosis, characterized by scar tissue formation, can ultimately result in liver failure. It's a major cause of morbidity and mortality globally, often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases. However, current treatment options are limited, highlighting the urgent need for the development of new therapies. As a reversible regulatory mechanism, epigenetic modification is implicated in many biological processes, including liver fibrosis. Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases, although the current evidence is still controversial. This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications, including DNA methylation, histone modification, and RNA modification, in liver fibrotic diseases. The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted. Finally, available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed. In summary, elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.

Abstract Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop‐CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop‐CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child–Pugh grades and the Model for End‐stage Liver Disease and Sodium (MELD‐Na) scores in the test and validation cohort. The EuroQol 5‐D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop‐CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

IntroductionThis study explores the influence of artificial intelligence (A.I.) applications on the job performance of healthcare providers, based on data from standardised-trained residents in the First People’s Hospital of Yunnan Province in China.MethodsThe ordinary least squares model is employed to examine the relationship between A.I. applications and job performance. To address potential endogeneity and missing variables, we utilise the propensity score matching method and alternative regression models.ResultsThe findings indicate that the job performance of standardised-trained residents positively correlates with A.I. applications. This relationship remains robust after addressing endogenous and missing variables. Further discussion reveals that patients’ support mediates the relationship between A.I. and job performance. Under identical conditions, the job performance of female residents empowered by A.I. is found to be significantly better than that of their male counterparts. Conversely, no heterogeneity is observed regarding the impact of A.I. on the job performance of medical practitioners and clinical medical technicians.DiscussionThis study underscores the positive role of A.I. applications in enhancing the job performance of standardised-trained residents. The results highlight the mediating role of patient support and suggest gender-based differences in the efficacy of A.I. empowerment.

Cochlear implant (CI) is a neural prosthesis that can restore hearing for patients with severe to profound hearing loss. Observed variability in auditory rehabilitation outcomes following cochlear implantation may be due to cerebral reorganization. Electroencephalography (EEG), favored for its CI compatibility and non-invasiveness, has become a staple in clinical objective assessments of cerebral plasticity post-implantation. However, the electrical activity of CI distorts neural responses, and EEG susceptibility to these artifacts presents significant challenges in obtaining reliable neural responses. Despite the use of various artifact removal techniques in previous studies, the automatic identification and reduction of CI artifacts while minimizing information loss or damage remains a pressing issue in objectively assessing advanced auditory functions in CI recipients. To address this problem, we propose an approach that combines machine learning algorithms—specifically, Support Vector Machines (SVM)—along with Independent Component Analysis (ICA) and Ensemble Empirical Mode Decomposition (EEMD) to automatically detect and minimize electrical artifacts in EEG data. The innovation of this research is the automatic detection of CI artifacts using the temporal properties of EEG signals. By applying EEMD and ICA, we can process and remove the identified CI artifacts from the affected EEG channels, yielding a refined signal. Comparative analysis in the temporal, frequency, and spatial domains suggests that the corrected EEG recordings of CI recipients closely align with those of peers with normal hearing, signifying the restoration of reliable neural responses across the entire scalp while eliminating CI artifacts.

Based on delay-Doppler maps (DDMs) in raw counts generated by spaceborne global navigation satellite system reflectometry (GNSS-R) receivers, retrieving ocean surface wind speeds is feasible, so several spaceborne GNSS-R missions have been carried out. However, it is currently troubled by global data latency of several hours or even more due to the bottleneck in the satellite downlink. Consequently, this article, for the first time, presents an algorithm for spaceborne GNSS-R receivers to conduct the DDM calibration in orbit and then to retrieve ocean surface wind speeds in real time, which contributes to not only lightening the burden on downloading a wealth of scientific data but also broadcasting real-time ocean surface wind speeds to users. Since there is a power correlation between direct and reflected signals from the same GNSS satellite with respect to the GNSS-R receiver, this algorithm calibrates direct signal power first, and then it estimates the real-time GNSS transmitter effective isotropic radiated power at the reflected signal according to the normalized antenna pattern of the corresponding GNSS satellite. Afterward, DDMs in raw counts are calibrated. Finally, ocean surface wind speeds are computed using pretrained geophysical model functions. Exploiting the scientific data from the GNOS-II onboard China's FY-3E satellite, this algorithm is validated carefully, and final retrieved ocean surface wind speeds against collocated European Centre for Medium-Range Weather Forecasts wind speeds have an overall root-mean-square error of 1.68 m/s and 1.50 m/s for GPS-R and BDS-R, respectively.

Abstract Salvia miltiorrhiza Bge. is a traditional Chinese medicine (TCM) that has been used for treatment of various diseases, including cancer by activating blood circulation and removing blood stasis. Tanshinone (TanIIA) and cryptotanshinone (CPT) are major lipophilic compounds extracted from the root of Salvia miltiorrhiza Bge., which are considered to be the effective compounds affecting the efficacy of the anti-tumor therapy of Salvia miltiorrhiza Bge. We have explored the mechanism of CPT and TanIIA exerting inhibition in non-small cell lung cancer (NSCLC) to provide experimental data support for guiding the translational development and clinical application of anti-tumor components of TCM. The subcutaneous tumor model and in vitro culture model of A549 cells was constructed to evaluate CPT and TanIIA's tumour-inhibitory effect respectively. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to CPT and TanIIA treatment. qRT-PCR and Western blot were used to explore the mechanism of CPT and TanIIA intervention on NSCLC. Both CPT and TanIIA significantly inhibited the proliferation of A549 tumor cells and tumor growth in animal models. After intervention, the migration ability decreased and the level of apoptosis increased. RNA-seq results showed that both CPT and TanIIA could cause gene differential expression, miR-21-5p as one of the most significant gene expression differences between the two groups, and could act on cell connectivity. CPT and TanIIA play a regulatory role in regulating tight junction proteins (Occludin and ZO1), and Occludin mRNA and protein levels were reduced in an in vitro miR-21-5p overexpression A549 cell model. The mechanisms may be related to the reduction of miR-21-5p expression to increase the level of promoted tight junction protein expression for the purpose of inhibiting proliferation and invasion of NSCLC.

Objective The aim of this study was to reveal the role and regulatory mechanism of miR-188-5p in the proliferation and differentiation of goat muscle satellite cells. Methods Goat skeletal muscle satellite cells isolated in the pre-laboratory were used as the test material. First, the expression of miR-188-5p in goat muscle tissues at different developmental stages was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, miR-188-5p was transfected into goat skeletal muscle satellite cells by constructing mimics and inhibitors of miR-188-5p, respectively. The changes of differentiation marker gene expression were detected by qPCR method. Results It was highly expressed in adult goat latissimus dorsi and leg muscles, goat fetal skeletal muscle, and at the differentiation stage of muscle satellite cells. Overexpression and interference of miR-188-5p showed that miR-188-5p inhibited the proliferation and promoted the differentiation of goat muscle satellite cells. Target gene prediction and dual luciferase assays showed that miR-188-5p could target the 3′untranslated region of the calcium/calmodulin dependent protein kinase II beta (CAMK2B) gene and inhibit luciferase activity. Further functional studies revealed that CAMK2B promoted the proliferation and inhibited the differentiation of goat muscle satellite cells, whereas si-CAMK2B restored the function of miR-188-5p inhibitor. Conclusion These results suggest that miR-188-5p inhibits the proliferation and promotes the differentiation of goat muscle satellite cells by targeting CAMK2B. This study will provide a theoretical reference for future studies on the molecular mechanisms of skeletal muscle development in goats.

To solve the problems of noise coverage defect and low contrast between the defect and the background of ZrO2 ceramic bearing balls, a surface defect extraction algorithm based on shearlet transform image enhancement for ZrO2 ceramic bearing balls is proposed. According to the shape characteristics of ceramic bearing balls, the surface defect image acquisition platform is built to collect and analyze surface defect images. Gaussian filtering weakens the scatter-particle noise in the image, and the threshold corrects the coefficient generated by the shearlet transform. After shearlet transform, the relatively low-frequency and high-frequency parts appear. The low-frequency part reflects the edge information of defects, and the high-frequency part reflects the edge and texture information of defects. Thus, the integrity of the defect is ensured, and an enhanced surface defect image is obtained. The gray histogram of the enhanced image is observed. The optimal threshold is selected by the histogram threshold segmentation method, and the process of defects being completely extracted from the background is realized. Experimental results showed that the extraction rates of pits, scratches, and cracks in ZrO2 ceramic bearing balls’ surface images are 95.00%, 92.50%, and 92.50%, respectively.

Background: Influenza and COVID-19 patients share similar features and outcomes amongst adults. However, the difference between these diseases is not explored in paediatric age group especially in terms of inflammatory markers, coagulation profile and outcomes. Hence, we did this review to compare the inflammatory, coagulation features and outcomes between influenza and COVID-19 infected children. Methods: Literature search was done in PubMed Central, Scopus, EMBASE, CINAHL, Cochrane library, Google Scholar & ScienceDirect from November 2019 to May 2022. Risk of bias assessment was done through Newcastle Ottawa scale. Meta-analysis was done using random-effects model and the final pooled estimate was reported as pooled odds ratio (OR) or standardized mean difference (SMD) along with 95 % confidence interval (CI) depending on the type of outcome. Results: About 16 studies were included with most studies having higher risk of bias. Influenza paediatric patients had significantly higher erythrocyte sedimentation rate (ESR) (pooled SMD = 0.60; 95%CI: 0.30–0.91; I2 = 0 %), lactate dehydrogenase (LDH) (pooled SMD = 2.01; 95%CI: 0.37–3.66; I2 = 98.4 %) and prothrombin time (PT) (pooled SMD = 2.12; 95%CI: 0.44–3.80; I2 = 98.3 %) when compared to paediatric COVID-19 patients. There was no significant difference in terms of features like CRP, procalcitonin, serum albumin, aPTT, mortality and need for mechanical ventilation. Conclusion: Inflammatory markers like ESR, LDH and PT was significantly higher in influenza patients when compared to COVID-19 in children, while rest of the markers and adverse clinical outcomes were similar between both the groups. Identification of these biomarkers has helped in understanding the distinctness of COVID-19 and influenza virus and develop better management strategies.

ABSTRACTThe importance of teaching the Luria-Delbrück experiment to biology students is increasingly recognized by educators, and improved pedagogical methods for teaching the classic experiment have been proposed and tested in the classroom. However, there are still obstacles that impede the proper teaching of the classic experiment. This note proposes two strategies to further improve the teaching of the classic experiment. The first strategy is to be frank with an inherent limitation of the classic experiment, and instructors should explain from a logical point of view why the classic experiment cannot be used to refute the possibility of directed mutation. The second strategy is to emphasize the pioneering work of Delbrück on developing the mutant distribution that enables researchers to estimate microbial mutation rates using data generated by fluctuation experiments, and instructors should shift their attention to the overlooked essential role of the mutant distribution.

Alpha rhythm slowing is an important electroencephalogram(EEG) feature associated with (AD). This study aims to understand the correlation between alpha band deceleration and molecular changes from the perspective of neural computing. Considering the effect of Aβ amyloid deposition on the inhibitory changes in the thalamic, a thalamic cortical model coupled with Aβ amyloid is established. The results show that Aβ amyloid deposition may induce neurotoxicity in thalamic reticular nucleus neurons, which results in inhibitory changes in the thalamus and slows the alpha rhythm of EEG output from the thalamus. In order to understand the pathogenesis more intuitively, some numerical simulations are provided to illustrate the obtained theories. This research is helpful to understand the pathogenesis of AD, so as to provide theoretical basis for the intervention and control of the disease.

Licorice is extensively utilized in the food industry, and glycyrrhetinic acid is among the most critical active constituents in licorice. This ingredient has garnered increasing attention in recent years. In a previous study, we identified a new series of Glycyrrhetinic acid derivatives containing piperazine skeleton, using virtual screening techniques based on docking. In this study, we conducted further optimization of the lead compound 4c, with a focus on enhancing the hydrophobic interactions in the binding site to improve agonist efficacy for peroxisome proliferator-activated receptor γ (PPARγ). The obtained compounds were characterized using 1H NMR, 13C NMR, HRMS, and HPLC. Furthermore, these compounds were evaluated strong antitumor activity. Some compounds with potent antitumor activities were tested for their PPARγ agonist activity. Especially, compound 4f showed the most potent antitumor activity with half maximal inhibitory concentration (IC50) values of 2.382 μM against the tested tumor cell lines Siha. Docking simulation was performed to position compound 4f into the PPARγ active site to determine the probable binding conformation. Consequently, we discovered a novel PPARγ agonist 4f that demonstrated high in vitro agonist activity.

C17H13F4NO4, monoclinic, P21/n (no. 14), a = 5.470(4) Å, b = 26.141(17) Å, c = 11.689(8) Å, β = 90.01°, V = 1671.3(19) Å3, Z = 4, Rgt${R}_{\mathit{gt}}$ (F) = 0.0612, wRref$w{R}_{\mathit{ref}}$ (F2) = 0.1650, T = 296(2) K.

Muscle fibers are the main component of skeletal muscle and undergo maturation through the formation of myotubes. During early development, a population of skeletal muscle satellite cells (SSCs) proliferate into myoblasts. The myoblasts then undergo further differentiation and fusion events, leading to the development of myotubes. However, the mechanisms involved in the transition from SSCs to myotube formation remain unclear. In this study, we characterized changes in the proteomic and transcriptomic expression profiles of SSCs, myoblasts (differentiation for 2 d) and myotubes (differentiation for 10 d). Proteomic analysis identified SLMAP and STOM as potentially associated with myotube formation. In addition, some different changes in MyoD, MyoG, Myosin7 and Desmin occurred after silencing SLMAP and STOM, suggesting that they may affect changes in the myogenic marker. GO analysis indicated that the differentiation and migration factors SVIL, ENSCHIG00000026624 (AQP1) and SERPINE1 enhanced the transition from SSCs to myoblasts, accompanied by changes in the apoptotic balance. In the myoblast vs. myotube group, candidates related to cell adhesion and signal transduction were highly expressed in the myotubes. Additionally, CCN2, TGFB1, MYL2 and MYL4 were identified as hub-candidates in this group. These data enhance our existing understanding of myotube formation during early development and repair.

Abstract Differential gene expression (DGE) analysis has been widely employed to identify genes expressed differentially with respect to a trait of interest using RNA sequencing (RNA-Seq) data. Recent RNA-Seq data with large samples pose challenges to existing DGE methods, which were mainly developed for dichotomous traits and small sample sizes. Especially, existing DGE methods are likely to result in inflated false positive rates. To address this gap, we employed a linear mixed model (LMM) that has been widely used in genetic association studies for DGE analysis of quantitative traits. We first applied the LMM method to the discovery RNA-Seq data of dorsolateral prefrontal cortex (DLPFC) tissue (n = 632) with four continuous measures of Alzheimer’s Disease (AD) cognitive and neuropathologic traits. The quantile–quantile plots of p-values showed that false positive rates were well calibrated by LMM, whereas other methods not accounting for sample-specific mixed effects led to serious inflation. LMM identified 37 potentially significant genes with differential expression in DLPFC for at least one of the AD traits, 17 of which were replicated in the additional RNA-Seq data of DLPFC, supplemental motor area, spinal cord, and muscle tissues. This application study showed not only well calibrated DGE results by LMM, but also possibly shared gene regulatory mechanisms of AD traits across different relevant tissues.

Boron(B)element is often utilized to enhance mechanical properties of stainless steel due to its excellent performance. In this study, selective laser melting (SLM) was used to print 316L/B stainless steel with varying boron weight content. The effects of boron content on microstructure, nanoindentation, and mechanical properties of the printed 316L stainless steel were discussed. Fine cell dendrites and columnar crystals were found in the SLM printed stainless steel due to the rapid solidification in SLM. It was found that boron has a higher growth limiting factor in the iron system and the boron solute can provide a high component supercooling. By adding boron element to stainless steel during printing, the honeycomb and grain size after solidification are significantly reduced due to interactions between the boron element and the 316L. Tensile testing results show that the ultimate tensile strength of the SLM fabricated parts with 0.5 wt% and 1 wt% boron element addition can be increased significantly to 1071 MPa and 1174 MPa, respectively.

Studying efficient and accurate soil heavy-metal detection technology is of great significance to establishing a modern system for monitoring soil pollution, early warning and risk assessment, which contributes to the continuous improvement of soil quality and the assurance of food safety. Laser-induced breakdown spectroscopy (LIBS) is considered to be an emerging and effective tool for heavy-metal detection, compared with traditional detection technologies. Limited by the soil matrix effect, the LIBS signal of target elements for soil heavy-metal detection is prone to interference, thereby compromising the accuracy of quantitative detection. Thus, a series of signal-enhancement methods are investigated. This study aims to explore the effect of conductive materials of NaCl and graphite on the quantitative detection of lead (Pb) in soil using LIBS, seeking to find a reliable signal-enhancement method of LIBS for the determination of soil heavy-metal elements. The impact of the addition amount of NaCl and graphite on spectral intensity and parameters, including the signal-to-background ratio (SBR), signal-to-noise ratio (SNR), and relative standard deviation (RSD), were investigated, and the mechanism of signal enhancement by NaCl and graphite based on the analysis of the three-dimensional profile data of ablation craters and plasma parameters (plasmatemperature and electron density) were explored. Univariate and multivariate quantitative analysis models including partial least-squares regression (PLSR), least-squares support vector machine (LS-SVM), and extreme learning machine (ELM) were developed for the quantitative detection of Pb in soil with the optimal amount of NaCl and graphite, and the performance of the models was further compared. The PLSR model with the optimal amount of graphite obtained the best prediction performance, with an Rp that reached 0.994. In addition, among the three spectral lines of Pb, the univariate model of Pb I 405.78 nm showed the best prediction performance, with an Rp of 0.984 and the lowest LOD of 26.142 mg/kg. The overall results indicated that the LIBS signal-enhancement method based on conductive materials combined with appropriate chemometric methods could be a potential tool for the accurate quantitative detection of Pb in soil and could provide a reference for environmental monitoring.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.

Objective: The objective of this study was to evaluate the therapeutic efficacy of ursodeoxycholic acid (UDCA) and mesenchymal stem cells (MSCs) in patients with severe COVID-19. Methods: We included severe COVID-19 patients hospitalized at Shulan (Hangzhou) Hospital between December 2022 and June 2023. We used a logistic regression model to compare the use of UDCA and MSCs in the two distinct groups of improved and poor outcomes. It is noteworthy that the deterioration group encompassed instances of both death and abandonment of treatment. The receiver operating characteristic (ROC) curve was plotted to assess the performance of the model. The aim was to assess the therapeutic effect of UDCA and MSCs on the outcome of severe COVID-19 patients. Results: A total of 167 patients with severe COVID-19 were included in this study. The analysis revealed that out of 42 patients (25.1%), 17 patients (10.2%) had taken UDCA, and 17 patients (10.2%) had used MSCs. Following a multivariable logistic regression, the results indicated a negative association between UDCA treatment (OR = 0.38 (0.16–0.91), p = 0.029), MSCs treatment (OR = 0.21 (0.07–0.65), p = 0.007), and the risk of severe COVID-19 mortality. Additionally, age showed a positive association with the risk of mortality (OR = 1.03 (1.01–1.07), p = 0.025). Conclusions: UDCA and MSCs have shown potential in improving the prognosis of severe COVID-19 patients and could be considered as additional treatments for COVID-19 in the future.

Stout beer was selected as the research object to screen angiotensin-converting enzyme (ACE) inhibitory peptides. The peptide sequences of stout beer were identified using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry with de novo, and 41 peptides were identified with high confidence. Peptide Ranker was used to score the biological activity and six peptides with a score ≥ 0.5 were screened to predict their potential ACE inhibitory (ACEI) activity. The toxicity, hydrophilicity, absorption, and excretion of these peptides were predicted. In addition, molecular docking between the peptides and ACE revealed a significant property of the peptide DLGGFFGFQR. Furthermore, molecular docking conformation and molecular dynamics simulation revealed that DLGGFFGFQR could be tightly bound to ACE through hydrogen bonding and hydrophobic interaction. Lastly, the ACEI activity of DLGGFFGFQR was confirmed using in vitro evaluation and the IC50 value was determined to be 24.45 μM.

Background: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by unknown causes and a poor prognosis. Recent research indicates that age-related mechanisms, such as cellular senescence, may play a role in the development of this condition. However, the relationship between cellular senescence and clinical outcomes in IPF remains uncertain. Methods: Data from the GSE70867 database were meticulously analyzed in this study. The research employed differential expression analysis, as well as univariate and multivariate Cox regression analysis, to pinpoint senescence-related genes (SRGs) linked to prognosis and construct a prognostic risk model. The model’s clinical relevance and its connection to potential biological processes were systematically assessed in training and testing datasets. Additionally, the expression location of prognosis-related SRGs was identified through immunohistochemical staining, and the correlation between SRGs and immune cell infiltration was deduced using the GSE28221 dataset. Result: The prognostic risk model was constructed based on five SRGs (cellular communication network factor 1, CYR61, stratifin, SFN, megakaryocyte-associated tyrosine kinase, MATK, C-X-C motif chemokine ligand 1, CXCL1, LIM domain, and actin binding 1, LIMA1). Both Kaplan-Meier (KM) curves (p = 0.005) and time-dependent receiver operating characteristic (ROC) analysis affirmed the predictive accuracy of this model in testing datasets, with respective areas under the ROC curve at 1-, 2-, and 3-years being 0.721, 0.802, and 0.739. Furthermore, qRT-RCR analysis and immunohistochemical staining verify the differential expression of SRGs in IPF samples and controls. Moreover, patients in the high-risk group contained higher infiltration levels of neutrophils, eosinophils, and M1 macrophages in BALF, which appeared to be independent indicators of poor prognosis in IPF patients. Conclusion: Our research reveals the effectiveness of the 5 SRGs model in BALF for risk stratification and prognosis prediction in IPF patients, providing new insights into the immune infiltration of IPF progression.

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

Summary: Background: With increasingly prevalent coexistence of chronic hepatitis B (CHB) and hepatic steatosis (HS), simple, non-invasive diagnostic methods to accurately assess the severity of hepatic inflammation are needed. We aimed to build a machine learning (ML) based model to detect hepatic inflammation in patients with CHB and concurrent HS. Methods: We conducted a multicenter, retrospective cohort study in China. Treatment-naive CHB patients with biopsy-proven HS between April 2004 and September 2022 were included. The optimal features for model development were selected by SHapley Additive explanations, and an ML algorithm with the best accuracy to diagnose moderate to severe hepatic inflammation (Scheuer's system ≥ G3) was determined and assessed by decision curve analysis (DCA) and calibration curve. This study is registered with ClinicalTrials.gov (NCT05766449). Findings: From a pool of 1,787 treatment-naive patients with CHB and HS across eleven hospitals, 689 patients from nine of these hospitals were chosen for the development of the diagnostic model. The remaining two hospitals contributed to two independent external validation cohorts, comprising 509 patients in validation cohort 1 and 589 in validation cohort 2. Eleven features regarding inflammation, hepatic and metabolic functions were identified. The gradient boosting classifier (GBC) model showed the best performance in predicting moderate to severe hepatic inflammation, with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.83–0.88) in the training cohort, and 0.89 (95% CI 0.86–0.92), 0.76 (95% CI 0.73–0.80) in the first and second external validation cohorts, respectively. A publicly accessible web tool was generated for the model. Interpretation: Using simple parameters, the GBC model predicted hepatic inflammation in CHB patients with concurrent HS. It holds promise for guiding clinical management and improving patient outcomes. Funding: This research was supported by the National Natural Science Foundation of China (No. 82170609, 81970545), Natural Science Foundation of Shandong Province (Major Project) (No. ZR2020KH006), Natural Science Foundation of Jiangsu Province (No.BK20231118), Tianjin Key Medical Discipline (Specialty), Construction Project, TJYXZDXK-059B, Tianjin Health Science and Technology Project key discipline special, TJWJ2022XK034, and Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission (2021022).

Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

ABSTRACT The dissemination of antibiotic resistance genes (ARGs) driven by mobile genetic elements (MGEs), especially among pathogenic bacteria, is of increasing global concern. Different from other well-characterized MGEs, integrative and conjugative elements (ICEs) have been lacking a comprehensive understanding of their roles in ARG propagation across bacterial phylogenies. Through genomic study based on a large collection of bacterial complete genomes and further comparative analysis with two prominent MGEs to spread ARGs—conjugative plasmids and class 1 integrons, we, for the first time, demonstrated that ICEs are indeed overlooked “hot” vectors from the aspects of mobility and pathogenicity: (i) ICEs exhibited broader phylogenetic distribution among two dominant phyla with high ARG diversity and (ii) ARG-carrying ICEs were significantly enriched in potential human pathogens covering all the six “ESKAPE” species, of which some displayed typical co-occurrence patterns with ARGs and virulence factors. Moreover, this first genomic comparative study also deciphered the distinct ARG profiles harbored by these three essential MGE groups in terms of diversity and prevalence, with characteristic ARG preference to each MGE group. Overall, our findings concerning the MGE-specific performance for ARG transmission, in particular, the historically understudied ICEs, could shed light on control strategy optimization to antibiotic resistance crises.IMPORTANCEDifferent from other extensively studied mobile genetic elements (MGEs) whose discoveries were initiated decades ago (1950s–1980s), integrative and conjugative elements (ICEs), a diverse array of more recently identified elements that were formally termed in 2002, have aroused increasing concern for their crucial contribution to the dissemination of antibiotic resistance genes (ARGs). However, the comprehensive understanding on ICEs’ ARG profile across the bacterial tree of life is still blurred. Through a genomic study by comparison with two key MGEs, we, for the first time, systematically investigated the ARG profile as well as the host range of ICEs and also explored the MGE-specific potential to facilitate ARG propagation across phylogenetic barriers. These findings could serve as a theoretical foundation for risk assessment of ARGs mediated by distinct MGEs and further to optimize therapeutic strategies aimed at restraining antibiotic resistance crises.

Abstract Kagome-lattice materials possess attractive properties for quantum computing applications, but their synthesis remains challenging. Herein, based on the compelling identification of the two cleavable surfaces of Co3Sn2S2, we show surface kagome electronic states (SKESs) on a Sn-terminated triangular Co3Sn2S2 surface. Such SKESs are imprinted by vertical p-d electronic hybridization between the surface Sn (subsurface S) atoms and the buried Co kagome-lattice network in the Co3Sn layer under the surface. Owing to the subsequent lateral hybridization of the Sn and S atoms in a corner-sharing manner, the kagome symmetry and topological electronic properties of the Co3Sn layer is proximate to the Sn surface. The SKESs and both hybridizations were verified via qPlus non-contact atomic force microscopy (nc-AFM) and density functional theory calculations. The construction of SKESs with tunable properties can be achieved by the atomic substitution of surface Sn (subsurface S) with other group III-V elements (Se or Te), which was demonstrated theoretically. This work exhibits the powerful capacity of nc-AFM in characterizing localized topological states and reveals the strategy for synthesis of large-area transition-metal-based kagome-lattice materials using conventional surface deposition techniques.

Abstract There is substantial evidence that albumin-bound paclitaxel (nab-paclitaxel) is effective and safe for the treatment of breast, lung and pancreatic cancers. However, it can still cause adverse effects by affecting cardiac enzymes, hepatic enzyme metabolism and blood routine related indicators, which affects the use of chemotherapy for a full course of treatment. However, there are no relevant clinical studies to systematically observe the effects and dynamics of albumin-bound paclitaxel on cardiac enzymes, liver enzyme metabolism, and routine blood-related indices. The purpose of our study was to determine the levels of serum creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), white blood cells (WBC) and hemoglobin (HGB) in cancer patients treated with albumin-conjugated paclitaxel. This study retrospectively analyzed 113 patients with cancer. Patients who had received two cycles of nab-paclitaxel 260 mg/m2 (administered intravenously on days 1, 8, and 15 of each 28-day cycle) were selected. Serum Cre, AST, ALT, LDH, CK, and CK-MB activities, WBC counts, and HGB levels were measured before and after treatment with two cycles. Fourteen cancer types were analyzed. The distribution of cancer types in patients was mainly concentrated in lung, ovarian, and breast cancer. Nab-paclitaxel treatment markedly decreased Cre, AST, LDH, and CK activities in the serum and WBC counts and HGB levels, respectively. Serum Cre and CK activities and HGB levels were remarkably downregulated at baseline compared to healthy controls. Patients receiving nab-paclitaxel treatment cause metabolic disorders in tumor patients by reducing the decrease of Cre, AST, LDH, CK, CK-MB, WBC and HGB indexes, thus inducing the occurrence of cardiovascular events, hepatotoxic events and fatigue and other symptoms. Therefore, for tumor patients, although receiving nab-paclitaxel improves the anti-tumor effect, it is still necessary to closely monitor the changes of related enzymatic and routine blood indicators, so as to detect and intervene at an early stage.

Phytophthora sojae is a type of pathogenic oomycete that causes Phytophthora root stem rot (PRSR), which can seriously affect the soybean yield and quality. To subvert immunity, P. sojae secretes a large quantity of effectors. However, the molecular mechanisms regulated by most P. sojae effectors, and their host targets remain unexplored. Previous studies have shown that the expression of PsAvh113, an effector secreted by Phytophthora sojae, enhances viral RNA accumulations and symptoms in Nicotiana benthamiana via VIVE assay. In this study, we analyzed RNA-sequencing data based on disease symptoms in N. benthamiana leaves that were either mocked or infiltrated with PVX carrying the empty vector (EV) and PsAvh113. We identified 1769 differentially expressed genes (DEGs) dependent on PsAvh113. Using stricter criteria screening and Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis of DEGs, we found that 38 genes were closely enriched in response to PsAvh113 expression. We selected three genes of N. benthamiana (NbNAC86, NbMyb4, and NbERF114) and found their transcriptional levels significantly upregulated in N. benthamiana infected with PVX carrying PsAvh113. Furthermore, individual silencing of these three genes promoted P. capsici infection, while their overexpression increased resistance to P. capsici in N. benthamiana. Our results show that PsAvh113 interacts with transcription factors NbMyb4 and NbERF114 in vivo. Collectively, these data may help us understand the pathogenic mechanism of effectors and manage PRSR in soybeans.

Lignin is insoluble in water, thereby limiting its use in the synthesis of adhesives. Therefore, in this study, an aminated lignin compound was prepared through a lignin amination reaction to increase the amount of raw lignin material that can be used in the synthesis of adhesives; moreover, structural analysis was conducted. The main result of this was the introduction of amino groups into phenolic hydroxyl groups in the hydrolyzing lignin from the raw lignin materials, thus generating the product of aminated lignin. The resulting particle sizes were about 100 nm, the average molecular weight was 57,627 g/mol, and the water solubility of the aminated lignin was about 0.45 g/100 mL. Therefore, the water solubility of raw lignin was greatly improved. The proposed reaction mechanism of phenolic hydroxyl groups and carboxylic acid groups in lignin is a reaction with ammonia molecules; thus, the successful introduction of amino groups generated the aminated lignin compounds. Hence, this article enriches the scientific theory of lignin reactions and provides a reference for the widespread application of raw lignin materials in the field of adhesives.

Abstract Background The importance of inflammation in thrombosis is increasingly appreciated. Neutrophil-lymphocyte ratio (NLR) and monocyte to high-density lipoprotein ratio (MHR) are important indicators of systemic inflammation. This study aimed to investigate the associations between NLR and MHR with left atrial appendage thrombus (LAAT) and spontaneous echo contrast (SEC) in patients with non-valvular atrial fibrillation. Methods This retrospective, cross-sectional study enrolled 569 consecutive patients with non-valvular atrial fibrillation. Multivariable logistic regression analysis was used to investigate independent risk factors of LAAT/SEC. Receiver operating characteristic (ROC) curves were used to evaluate the specificity and sensitivity of NLR and MHR in predicting LAAT/SEC. Subgroup and Pearson correlation analyses were used to assess the correlations between NLR and MHR with the CHA2DS2-VASc score. Results Multivariate logistic regression analysis showed that NLR (OR: 1.49; 95%CI: 1.173–1.892) and MHR (OR: 2.951; 95%CI: 1.045–8.336) were independent risk factors for LAAT/SEC. The area under the ROC curve of NLR (0.639) and MHR (0.626) was similar to that of the CHADS2 score (0.660) and CHA2DS2-VASc score (0.637). Subgroup and Pearson correlation analyses showed significant but very weak associations between NLR (r = 0.139, P

Abstract Objective The purpose of this study was to explore whether miR-494-3p inhibits the occurrence of mitochondrial autophagy in cardiomyocytes by inhibiting the expression of PGC1-α and to supplement the theoretical basis for the role of autophagy in cardiac injury induced by hypoxia/reperfusion (H/R). Methods The expression of miR-494-3p was detected by RT‒qPCR, and the expression of PGC1-α, autophagy-related proteins (LC3, Beclin 1), apoptosis-related proteins (Bax and Bcl-2), PINK1/Parkin signaling pathway-related proteins (PINK1, Parkin) and mitochondrial change-related proteins (Mfn1, Mfn2, OPA1) was detected by Western blotting. The changes in mitochondrial membrane potential were detected by JC-1 staining (ΔΨm). The formation of autophagosomes was observed by transmission electron microscopy. Cell proliferation activity was detected by CCK-8, and cell apoptosis was detected by flow cytometry. A dual-luciferase gene reporter assay identified a targeted binding site between miR-494-3p and PGC1-α. Results The results showed that miR-494-3p and PGC1-α were differentially expressed in H/R cardiomyocytes; that is, the expression of miR-494-3p was downregulated, and the expression of PGC1-α was upregulated. In addition, mitochondrial autophagy occurred in H/R cardiomyocytes. That is, LC3-II/LC3-I, Beclin 1, PINK1, and Parkin expression was upregulated, Mfn1, Mfn2, and OPA1 expression was downregulated, and the mitochondrial membrane potential was decreased. The transfection of miR-494-3p mimic can significantly improve the cell proliferation activity of cardiomyocytes and inhibit the occurrence of cardiomyocyte apoptosis and autophagy, while the transfection of miR-494-3p inhibitor has the opposite result. After transfection of the miR-494-3p mimic, treatment with autophagy inhibitors and activators changed the effects of miR-494-3p on cardiomyocyte proliferation and apoptosis. At the same time, the overexpression of PGC1-α reversed the promoting effect of miR-494-3p on cardiomyocyte proliferation and the inhibitory effect on apoptosis and autophagy. Conclusion MiR-494-3p can target and negatively regulate the expression of PGC1-α to inhibit mitophagy in cardiomyocytes.

Abstract The Cape Horn Current (CHC) is one of the components of the Antarctic Circumpolar Current system that enables it to fulfill its crucial role as a conduit between ocean basins. Despite this, to‐date there have been very few measurements of CHC strength and none continuous in time or space. Here, we use a combination of ocean models, one free‐running and one data‐assimilating, and satellite altimetry (1993–2021) to estimate the time‐dependent strength of the CHC at 10 transects along its length. We find the time‐mean CHC transport increases from 0.4 ± 0.5 Sv near 49°S to 5.3 ± 2.2 Sv at Cape Horn, with peak‐to‐peak interannual fluctuations of 0.8–3.4 Sv. Although, theoretically, increased run‐off from a wasting Patagonian Ice‐field would strengthen its flow, the CHC appears quite stable over the last 29 years, with little evidence of a coherent, long‐term increase or decrease in the strength of the current.

Shigellosis (bacillary dysentery) is a severe gastrointestinal infection with a global incidence of 90 million cases annually. Despite the severity of this disease, there is currently no licensed vaccine against shigellosis. Shigella’s primary virulence factor is its type III secretion system (T3SS), which is a specialized nanomachine used to manipulate host cells. A fusion of T3SS injectisome needle tip protein IpaD and translocator protein IpaB, termed DBF, when admixed with the mucosal adjuvant double-mutant labile toxin (dmLT) from enterotoxigenic E. coli was protective using a murine pulmonary model. To facilitate the production of this platform, a recombinant protein that consisted of LTA-1, the active moiety of dmLT, and DBF were genetically fused, resulting in L-DBF, which showed improved protection against Shigella challenge. To extrapolate this protection from mice to humans, we modified the formulation to provide for a multivalent presentation with the addition of an adjuvant approved for use in human vaccines. Here, we show that L-DBF formulated (admix) with a newly developed TLR4 agonist called BECC438 (a detoxified lipid A analog identified as Bacterial Enzymatic Combinatorial Chemistry candidate #438), formulated as an oil-in-water emulsion, has a very high protective efficacy at low antigen doses against lethal Shigella challenge in our mouse model. Optimal protection was observed when this formulation was introduced at a mucosal site (intranasally). When the formulation was then evaluated for the immune response it elicits, protection appeared to correlate with high IFN-γ and IL-17 secretion from mucosal site lymphocytes.

Twisted 2D materials have recently emerged as a controllable quantum simulator platform. Here, the authors apply the same approach to tune the edge states of zigzag graphene nanoribbons, showing a unique degree of freedom represented by the lateral stacking offset of the 1D nanostructures.

With the advantages of flexible parking locations and convenient cycling, Dockless Bicycle-sharing (DBS) has become increasingly popular worldwide. However, with the massive increase of DBSs and electric fences, DBS systems face several challenges: (1) the hardness of identifying the DBS tidal zones; (2) the difficulty of accurately evaluating and identifying overload fences; (3) the issues of rebalancing DBS in time. To deal with these challenges, we propose a Dockless Bicycle-sharing Dynamic Rebalance (DBSDR) system to dynamically provide the optimal bicycle guidance for the DBS network. The DBSDR system contains three modules: DBS tidal zone identification, evaluation framework of overload fences, and DBS dynamic guidance. For DBS tidal zone identification, tidal zone identification and location from each fence with bicycle flows are provided with the HDBSCAN clustering method. The evaluation framework, covering DBS flows and the parking demand density, is proposed to assess the characteristics of overload fences. Finally, a DBS dynamic guidance method is provided to balance DBS for the tidal phenomenon with guiding users to the optimal target fence. Extensive experiments conducted on real-world DBS datasets show the effectiveness and accuracy of rebalancing the tidal phenomenon in the DBS system.

Abstract Background Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD. Methods The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases. Results Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18–0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P

Cholangiopathies lack effective medicines and can progress into end-stage liver diseases. Mining natural product transcriptome databases for bioactive ingredients, which can reverse disease-associated transcriptomic phenotypes, holds promise as an effective approach for drug discovery. To identify disease-associated transcriptomic changes, we performed RNA-sequencing on bile duct ligation (BDL)-induced cholestatic liver fibrosis mice, as well as PBC and PSC patients, and found that PANoptosis and activation of type-I interferon (IFN) signaling were observed in BDL mice and patients with PBC and PSC. We then established a transcriptotype-driven screening system based on HERB and ITCM databases. Among 283 natural ingredients screened, apigenin (Api), which is widely distributed in varieties of food and medicinal plants, was screened out by our screen system since it reversed the expression pattern of key genes associated with PANoptosis and type-I IFN responses. In BDL, Abcb4−/−, and DDC-fed mice, Api effectively ameliorated liver injuries, inflammation, and fibrosis. It also protected cholangiocytes from bile acid-stimulated PANoptosis, thus alleviating damage-associated molecular pattern-mediated activation of TBK1-NF-κB in macrophages. Additionally, Api directly inhibited type-I IFN-induced downstream inflammatory responses. Our study demonstrated the pathogenic roles of PANoptosis and type-I IFN signaling in cholestatic liver fibrosis and verified the feasibility of transcriptotype-based drug screening. Furthermore, this study revealed a novel anti-inflammatory mechanism of Api and identified it as a promising candidate for the treatment of cholestatic liver fibrosis.

Ruthenium is required to separate from high-level liquid waste (HLLW) because Ru is a valuable resource and is negatively influential on the vitrification process of HLLW. However, the separation of Ru is very challenging due to its complicated complexation properties. In this study, the adsorption and desorption characteristics of ruthenium on a synthesized SiPyR-N3 (weak-base anion exchange resin with pyridine functional groups) composite were investigated in nitric acid and nitrite–nitric acid systems, respectively, and the adsorption mechanism was explored. The experimental results showed that SiPyR-N3 has a significantly better adsorption effect on Ru in the nitrite–nitric acid system than in the nitric acid system, with an increase in the adsorption capacity of approximately three times. The maximum adsorption capacity of Ru is 45.6 mg/g in the nitrite–nitric acid system. The SiPyR-N3 possesses good adsorption selectivity (SFRu/other metal ions is around 100) in 0.1 M NO2−–0.1 M HNO3 solution. The adsorption processes of Ru in the two different systems are fitted with the pseudo-second-order kinetic model and Langmuir model for uptake kinetics and adsorption isotherms, respectively. The results obtained from the FT-IR, XPS, and UV absorption spectrometry indicate that NO2− was involved in the adsorption process either as a complexing species with the metal ions or as free NO2− from the solution. A 0.1 M HNO3 + 1 M thiourea mixed solution shows effective desorption performance, and the desorption efficiency can reach 92% at 328 K.

Ferula is a genus of flowering plants known for its edible and medicinal properties. Since ancient times, many species of Ferula have been used in traditional medicine to treat various health issues across countries, such as digestive disorders, respiratory problems, and even as a remedy for headaches and toothaches. In addition, they are also used as a flavoring agent in various cuisines. As the main active ingredients in Ferula, sesquiterpenes and their derivatives, especially sesquiterpene coumarins, sesquiterpene phenylpropanoids, and sesquiterpene chromones, have attracted the attention of scientists due to the diversity of their chemical structures, as well as their extensive and promising biological properties, such as antioxidative, anti-inflammatory, antibacterial properties. However, there has not been a comprehensive review of sesquiterpenes and their derivatives from this plant. This review aims to provide an overview of the chemical structures, biosynthetic pathways, and biological properties of sesquiterpenes and sesquiterpene derivatives from Ferula, which may help guide future research directions and possible application methods for this valuable edible and medicinal plant.

ABSTRACT The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as Staphylococcus aureus. The endogenous skin microbiota limits S. aureus colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant S. aureus (MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had a little discernable effect on community diversity though the overall microbial load was sensitive to multiple types of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Using genomic and phenotypic criteria, we curated three isolates to investigate whether prophylactic colonization would inhibit MRSA colonization in vivo. The three-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection. IMPORTANCE The skin microbiota is protective against pathogens or opportunists such as S. aureus, the most common cause of skin and soft tissue infections. S. aureus can colonize normal skin and nasal passages, and colonization is a risk factor for infection, especially on breach of the skin barrier. Here, we established a pig model to study the competitive mechanisms of the skin microbiota and their role in preventing colonization by MRSA. This drug-resistant strain is also a livestock pathogen, and swine herds can be reservoirs of MRSA carriage. From 7,700 cultured skin isolates, we identified 37 unique species across three phyla that inhibited MRSA. A synthetic community of three inhibitory isolates provided protection together, but not individually, in vivo in a murine model of MRSA colonization. These findings suggest that antagonism is widespread in the pig skin microbiota, and these competitive interactions may be exploited to prevent MRSA colonization.