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This study explored the change of tetracycline degradation efficiency, metabolic pathway, soil physiochemical properties and degraders in vermiremediation by two earthworm species of epigeic Eisenia fetida and endogeic Amynthas robustus. We found a significant acceleration of tetracycline degradation in both earthworm treatments, and 4-epitetracycline dehydration pathway was remarkably enhanced only by vermiremediation. Tetracycline degraders from soils, earthworm intestines and casts were different. Ralstonia and Sphingomonas were potential tetracycline degraders in soils and metabolized tetracycline through direct dehydration pathway. Degraders in earthworm casts (Comamonas , Acinetobacter and Stenotrophomonas) and intestines (Pseudomonas and Arthrobacter) dehydrated 4-epitetracycline into 4-epianhydrotetracycline. More bacterial lineages resisting tetracycline were found in earthworm treatments, indicating the adaptation of soil and intestinal flora under tetracycline pressure. Earthworm amendment primarily enhanced tetracycline degradation by neutralizing soil pH and consuming organic matters, stimulating both direct dehydration and epimerization-dehydration pathways. Our findings proved that vermicomposting with earthworms is effective to alter soil microenvironment and accelerate tetracycline degradation, behaving as a potential approach in soil remediation at tetracycline contaminated sites. [Display omitted] • Accelerated tetracycline degradation by both E. fetida and A. robustus. • Earthworms neutralize soil pH, consume organic matter and shift bacterial community. • Different tetracycline degraders and metabolites between earthworm gut or casts and soils. • A new epimerization-dehydration pathway in vermicomposting treatment. [ABSTRACT FROM AUTHOR]

The use of probiotics poses challenges represented in loss of viability during harsh conditions, hence this study aims at exploring a simple green method to increase the survival of the encapsulated Lactobacillus salivarius during gastrointestinal conditions, thermal treatment, and storage. Single and dual biopolymer beads which consisted of whey protein, alginate, carboxymethyl cellulose, and chitosan were fabricated and then characterized by fourier transform infrared (FTIR) spectra. The morphology characteristics were investigated using scanning electron microscopy (SEM) and fluorescence microscopy. The encapsulation efficiency was reached up to 96% in all treatments. A biopolymer coated by a layer of carboxymethyl cellulose or chitosan showed a great protection for probiotics upon exposure to gastrointestinal fluid. Also, a high protection was observed after thermal treatment and storage when compared with free cells. Approximately the release of cells in colon solution was noted after 18 h for all treatments. • Biopolymer beads were formed through a simple green developed method. • Electrostatic and hydrogen bonds enhanced stability of biopolymer. • Dual biopolymer beads resulted in higher survivability compared to single biopolymer and free cells. • Biopolymer beads succeeded in delivered probiotics to the colon with high viability. [ABSTRACT FROM AUTHOR]

The influence of pH (2–7) on the interfacial and emulsifying properties of β-conglycinin/pectin (7S/PC) mixtures was investigated. At pH 2–3 (pH < pI of 7S), 7S/PC mixtures had large size and low Zeta potential, leading to slower adsorption kinetics. When treated by deformation amplitude in the non-linear region, Lissajous plots of 7S/PC mixtures at pH 3 suggested that PC might adsorb onto the interfaces through competitive adsorption as proved by viscous behavior response. These combinations effects resulted in poor emulsification properties and emulsions instability. At pH = 5–7 (pH > pI of 7S), 7S/PC mixtures had smaller size and higher Zeta-potential values, leading to the rapid adsorption. Lissajous plots of 7S/PC mixtures at pH 6 suggested that 7S almost irreversibly adsorbed onto the interface as proved by a purely elastic response. Particle sizes of emulsions stabilized by 7S/PC mixtures at pH 6–7 remained unchanged due to that PC provided electrostatic and steric stabilization. In summary, pH had significant effects on the interactions between 7S and PC, and thereby influenced the interfacial and emulsifying properties of their mixtures. Image 1 • pH affected the interfacial and emulsifying properties of 7S/PC mixtures. • 7S/PC mixtures facilitated emulsion stability at pH 6–7 but emulsion instability at pH 2-3. • Lissajous plots of 7S/PC mixtures at pH 3 suggested competitive adsorption of PC. • Lissajous plots of 7S/PC mixtures at pH 6 suggested irreversible adsorption of 7S. [ABSTRACT FROM AUTHOR]

Oxidative stress caused by the excess of radical oxygen species (ROS) could lead to many kinds of human diseases. Antioxidant peptides, a kind of natural antioxidants, have attracted much attention for their low toxicities and strong antioxidant activities. Food proteins can be regarded as good materials for the production of antioxidant peptides by enzymatic hydrolysis. In this work, we aimed to find novel natural antioxidant peptides derived from Agrocybe aegerita proteins by enzymatic hydrolysis. The method of response surface methodology (RSM) was adopted for optimizing the hydrolysis parameters. Under the optimal condition, antioxidant peptides of Agrocybe aegerita were separated and sequenced. Finally, twenty-five novel antioxidant peptides with high antioxidant scores were identified. These results suggest that the hydrolysates of Agrocybe aegerita proteins could be used as natural antioxidants in functional foods and food processing. • Hydrolysates of Agrocybe aegerita proteins can be used as natural antioxidants in food. • Reaction temperature is an important factor to affect the antioxidant activities of hydrolysates. • Twenty-five novel antioxidant peptides scoring more than 5 were identified. [ABSTRACT FROM AUTHOR]

This study systematically investigated the binding mechanism between capsaicin (CAP) and β-lactoglobulin (β-lg) through the method of multi-spectroscopic, thermodynamics, molecular docking, and molecular dynamics simulation at pH 7.4. The results showed that CAP could interact with β-lg to enhance the fluorescence intensity of β-lg. Simultaneously, the complex formed by CAP and β-lg enhanced the hydrophobicity of the microenvironment of Trp and Tyr in β-lg. The change in particle size without changing the secondary structure of β-lg indicates a transition between the large aggregate particle to small aggregate particle of β-lg. Isothermal titration calorimetric (ITC) results show that hydrophobic interactions play an important role in the formation of the complex. The MD simulation results showed that the RMSD of the systems reached equilibrium and wiggle around the mean value after 30 ns of simulation time. Analysis of Rg indicated that β-lg and β-lg/CAP complex was stabilized around 30 ns. Secondary structure analysis results showed that CAP has no distinct effect on the β-lg structure. Furthermore, the van der Waals interactions are also involved in binding between β-lg and CAP according to the result of MD simulation. The calculational results indicated that CAP preferred to bind to the hydrophobic pocket of β-lg. The obtained results could provide some new clues to the interaction mechanism of β-lg and CAP, which proved that β-lg possesses the ability to apply in functional food as the vehicle of capsaicin. Image 1 • The binding between β-lg and CAP change from endothermic to exothermic process from ITC results. • The van der Waals interactions and hydrophobic interactions are involved in binding between β-lg and CAP. • The CAP has a high affinity for the reaction with β-lg. [ABSTRACT FROM AUTHOR]

By analyzing the principle of pressure balance in the sealing area, a more stable and faster convergence fluid–solid coupling numerical algorithm is proposed. The overall flexibility matrix of fluid film and asperities is extracted from both fluid and contact mechanics analyses. Then, multiplying the flexibility matrix by the current unbalanced pressure yields the required film thickness correction. Through some example analysis, it can be found the present model can be set with a larger relaxation factor (0.1) or even do not need any relaxation, while conventional model usually need to sacrifice efficiency and choose a smaller relaxation factor (0.001) to achieve stable convergence, meaning that the stability of the present model can be ensured at a higher convergence rate. • The total flexibility matrix of the system is needed to modify the film thickness. • The present model do not need any relaxation. • The calculation process is more stable than traditional method. • The calculation time cost by the present model is much less. [ABSTRACT FROM AUTHOR]

Atrazine is one of the most used herbicides, posing non-neglectable threats to ecosystem and human health. This work studied the performance and mechanisms of surface-modified biochar in accelerating atrazine biodegradation by exploring the changes in atrazine metabolites, bacterial communities and atrazine degradation-related genes. Among different types of biochar, nano-hydroxyapatite modified biochar achieved the highest degradation efficiency (85.13 %), mainly attributing to the increasing pH, soil organic matter, soil humus, and some enriched indigenous bacterial families of Bradyrhizobiaceae, Rhodospirillaceae, Methylophilaceae, Micrococcaceae, and Xanthobacteraceae. The abundance of 4 key atrazine degradation-related genes (atzA, atzB, atzC and triA) increased after biochar amendment, boosting both dechlorination and dealkylation pathways in atrazine metabolism. Our findings evidenced that biochar amendment could accelerate atrazine biodegradation by altering soil physicochemical properties, microbial composition and atrazine degradation pathways, providing clues for improving atrazine biodegradation performance at contaminated sites., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Stress urinary incontinence (SUI) is a common disease that seriously affects the quality of life of patients. In recent years, studies have shown that apolipoprotein E (ApoE) plays a role in neuroprotection and repair, but its specific role in SUI remains unclear. The aim of this study was to investigate the effect of macromolecular protein ApoE related markers on the prognosis of rats with SUI treated by modified Buzhong Yiqi Decoction (MBZYQD), in order to provide a new target for the treatment of SUI. Healthy rats were selected to establish a SUI model and divided into groups. The levels of ApoE related metabolites in blood of rats were detected by Metabolomics analysis and Lipidomics analysis. The urine leakage point pressure (LPP) were compared in each group, and the therapeutic effect of MBZYQD was evaluated. Compared with the model group, the LPP of rats in MBZYQD supplemented group was significantly higher. Compared with the control group, the LPP of MBZYQD was not statistically significant before and after treatment. The macromolecular protein ApoE may plays a key role in the treatment of SUI by MBZYQD, which can improve symptoms by regulating lipid metabolism repair., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Deep neural networks (DNNs) have demonstrated remarkable performance in many fields, and deploying them on resource-limited devices has drawn more and more attention in industry and academia. Typically, there are great challenges for intelligent networked vehicles and drones to deploy object detection tasks due to the limited memory and computing power of embedded devices. To meet these challenges, hardware-friendly model compression approaches are required to reduce model parameters and computation. Three-stage global channel pruning, which involves sparsity training, channel pruning, and fine-tuning, is very popular in the field of model compression for its hardware-friendly structural pruning and ease of implementation. However, existing methods suffer from problems such as uneven sparsity, damage to the network structure, and reduced pruning ratio due to channel protection. To solve these issues, the present article makes the following significant contributions. First, we present an element-level heatmap-guided sparsity training method to achieve even sparsity, resulting in higher pruning ratio and improved performance. Second, we propose a global channel pruning method that fuses both global and local channel importance metrics to identify unimportant channels for pruning. Third, we present a channel replacement policy (CRP) to protect layers, ensuring that the pruning ratio can be guaranteed even under high pruning rate conditions. Evaluations show that our proposed method significantly outperforms the state-of-the-art (SOTA) methods in terms of pruning efficiency, making it more suitable for deployment on resource-limited devices.

Competing Interests: None declared.

Study Question: What is the significance of visceral adipose tissue (VAT) in the pathogenesis of polycystic ovary syndrome (PCOS) and its impact on the regulation of metabolic disorders in women with PCOS?, Summary Answer: We revealed a potentially causal relationship between increased genetically predicted VAT and PCOS-related traits, and found that VAT exhibited impaired glucose metabolism and mitochondrial oxidative phosphorylation (OXPHOS) in women with PCOS., What Is Known Already: PCOS is a common reproductive endocrine disorder accompanied by many metabolic abnormalities. Adipose tissue is a metabolically active endocrine organ that regulates multiple physiological processes, and VAT has a much stronger association with metabolism than subcutaneous adipose tissue does., Study Design, Size, Duration: Mendelian randomization (MR) analysis was used to investigate the potential causal association between genetically predicted VAT and the risk of PCOS. Data for MR analysis were extracted from European population cohorts. VAT samples from sixteen PCOS patients and eight control women who underwent laparoscopic surgery were collected for proteomics and targeted metabolomics analyses., Participants/materials, Setting, Methods: PCOS was diagnosed according to the 2003 Rotterdam Criteria. The control subjects were women who underwent laparoscopic investigation for infertility or benign indications. Proteomics was performed by TMT labeling and liquid chromatography-tandem mass spectrometry analysis, and targeted metabolomics was performed by ultra-performance liquid chromatography-tandem mass spectrometry analysis. The key differentially expressed proteins (DEPs) were validated by immunoblotting., Main Results and the Role of Chance: MR analysis revealed a potentially causal relationship between increased genetically predicted VAT and PCOS, as well as related traits, such as polycystic ovaries, total testosterone, bioavailable testosterone, and anti-Müllerian hormone, while a negative relationship was found with sex hormone-binding globulin. Enrichment pathway analysis of DEPs indicated the inhibition of glycolysis and activation of mitochondrial OXPHOS in the VAT of PCOS patients. MR analysis revealed that key DEPs involved in glycolysis and OXPHOS were significantly linked to PCOS and its related traits. Dot blot assay confirmed a significant decrease in glycolysis enzymes PKM2 and HK1, and an increase in mitochondrial Complex I and III subunits, NDUFS3 and UQCR10. Moreover, metabolomics analysis confirmed down-regulated metabolites of energy metabolic pathways, in particular glycolysis. Further analysis of PCOS and control subjects of normal weight revealed that dysregulation of glucose metabolism and OXPHOS in VAT of women with PCOS was independent of obesity., Large Scale Data: The mass spectrometry proteomics data have been deposited to the iProX database (http://www.iprox.org) with the iProX accession: IPX0005774001., Limitations, Reasons for Caution: There may be an overlap in some exposure and outcome data, which might affect the results in the MR analysis., Wider Implications of the Findings: The changes in protein expression of key enzymes affect their activities and disrupt the energy metabolic homeostasis in VAT, providing valuable insight for identifying potential intervention targets of PCOS., Study Funding/competing Interest(s): This work was supported by the National Key Research and Development Project of China (2021YFC2700402), the National Natural Science Foundation of China (82071608, 82271665), the Key Clinical Projects of Peking University Third Hospital (BYSY2022043), and the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001). All authors report no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study aims to predict bone metastasis in lung cancer patients using radiomics and deep learning. Early prediction of bone metastasis is crucial for timely intervention and personalized treatment plans. This can improve patient outcomes and quality of life. By integrating advanced imaging techniques with artificial intelligence, this study seeks to enhance predictive accuracy and clinical decision-making., Methods: We included 189 lung cancer patients, comprising 89 with non-bone metastasis and 100 with confirmed bone metastasis. Radiomic features were extracted from CT images, and feature selection was performed using Minimum Redundancy Maximum Relevance (mRMR) and Least Absolute Shrinkage and Selection Operator (LASSO). We developed and validated a radiomics model and a deep learning model using DenseNet-264. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Statistical comparisons were made using the DeLong test., Results: The radiomics model achieved an AUC of 0.815 on the training set and 0.778 on the validation set. The DenseNet-264 model demonstrated superior performance with an AUC of 0.990 on the training set and 0.971 on the validation set. The DeLong test confirmed that the AUC of the DenseNet-264 model was significantly higher than that of the radiomics model (p < 0.05)., Conclusions: The DenseNet-264 model significantly outperforms the radiomics model in predicting bone metastasis in lung cancer patients. The early and accurate prediction provided by the deep learning model can facilitate timely interventions and personalized treatment planning, potentially improving patient outcomes. Future studies should focus on validating these findings in larger, multi-center cohorts and integrating clinical data to further enhance predictive accuracy., Competing Interests: This research is supported by the Fujian Provincial Natural Science Foundation of China (2023J01895) and the Science and Technology Program of Quanzhou (2021CT0010)., (© 2024 The Authors. Published by Elsevier GmbH.)

To identify core and bridge nodes in the network structure of alexithymia and cognitive emotion regulation strategies in community-dwelling older adults, and compare network differences among older adults with different health statuses, we recruited 677 participants and network analysis was performed in R 4.2.0. After including the covariates, the nodes Catastrophizing, Difficulty Identifying feelings, and Refocusing on Planning ranked as the top three. The nodes Externally Oriented Thoughts and Difficulty Identifying Feelings were identified as bridge nodes based on bridge strength values. Significant differences were observed between the healthy and comorbidity groups, and also between the single chronic disease and comorbidity groups (p < 0.05). Catastrophizing, Difficulty Identifying Feelings, and Refocusing on Planning were the core nodes, and Externally Oriented Thoughts and Difficulty Identifying Feelings were the key bridge nodes. The network structure of comorbidity in older adults was characterized by stronger ties to non-adaptive cognitive emotion regulation strategies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pulsed electromagnetic field (PEMF) therapy has been extensively investigated in clinical studies for the treatment of angiogenesis-related diseases. However, there is a lack of research on the impact of PEMFs on energy metabolism and mitochondrial dynamics during angiogenesis. The present study included tube formation and CCK-8 assays. A Seahorse assay was conducted to analyze energy metabolism, and mitochondrial membrane potential assays, mitochondrial imaging, and reactive oxygen species assays were used to measure changes in mitochondrial structure and function in human umbilical vein endothelial cells (HUVECs) exposed to PEMFs. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of antioxidants, glycolytic pathway-related genes, and genes associated with mitochondrial fission and fusion. The tube formation assay demonstrated a significantly greater tube network in the PEMF group compared to the control group. The glycolysis and mitochondrial stress tests revealed that PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis. Mitochondrial imaging revealed a wire-like mitochondrial morphology in the control group, and treatment with PEMFs led to shorter and more granular mitochondria. Our major findings indicate that exposure to PEMFs accelerates angiogenesis in HUVECs, likely by inducing energy metabolism reprogramming and mitochondrial fission., (© 2024. The Author(s).)

Multidimensional metabolic analysis has become a new trend in establishing efficient disease monitoring systems, as the constraints associated with relying solely on a single dimension in refined monitoring are increasingly pronounced. Here, coordination polymers are employed as derivative precursors to create multishell hollow hybrids, developing an integrated metabolic monitoring system. Briefly, metabolic fingerprints are extracted from hundreds of serum samples and urine samples, encompassing not only membranous nephropathy but also related diseases, using high-throughput mass spectrometry. With optimized algorithm and initial feature selection, the established combined panel demonstrates enhanced accuracy in both subtype differentiation (over 98.1%) and prognostic monitoring (over 95.6%), even during double blind test. This surpasses the serum biomarker panel (≈90.7% for subtyping, ≈89.7% for prognosis) and urine biomarker panel (≈94.4% for subtyping, ≈76.5% for prognosis). Moreover, after attempting to further refine the marker panel, the blind test maintains equal sensitivity, specificity, and accuracy, showcasing a comprehensive improvement over the single-fluid approach. This underscores the remarkable effectiveness and superiority of the integrated strategy in discriminating between MN and other groups. This work has the potential to significantly advance diagnostic medicine, leading to the establishment of more effective strategies for patient management., (© 2024 Wiley‐VCH GmbH.)

COVID-19 has already claimed over 7 million lives and has infected over 775 million people globally [1]. SARS-CoV-2, the virus that causes Covid-19, spreads primarily through droplets from infected people's airways, rendering Heating, Ventilation, and Air Conditioning (HVAC) systems critical in controlling infection risk levels in the indoor environment. To understand the dynamics of exhaled droplets and aerosols and the percentage of particles that are inhaled, escaped, recirculated, or trapped on different surfaces for a variety of environmental settings, we have presented our findings from the Computational Fluid Dynamics (CFD) modeling to investigate the impact of changing HVAC parameters in this paper. When combined with the spatial and temporal distribution of droplets, this method can be used to assess the potential risk and strengthen resilience. This finding demonstrates the viability and usefulness of CFD for modeling the distribution and dynamics of droplets and aerosols in confined environments. Our study demonstrates that raising the Air Change per Hour (ACH) from 2 to 8 reduces the risk of particle inhalation by nearly 70 %. Additionally, limiting the amount of air recirculation or increasing the amount of fresh air helps to reduce the number of airborne particles in an indoor space. To reduce the potential for respiratory droplet-related transmission and to provide relevant recommendations to the appropriate authority, the same computational approach could be applied to a wide range of ventilated indoor environments such as public buses, restaurants, exhibitions, and theaters., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Kinase-targeted inhibitors hold promise for new therapeutic options, with multi-target inhibitors offering the potential for broader efficacy while minimizing polypharmacology risks. However, comprehensive experimental profiling of kinome-wide activity is expensive, and existing computational approaches often lack scalability or accuracy for understudied kinases. We introduce KinomeMETA, an artificial intelligence (AI)-powered web platform that significantly expands the predictive range with scalability for predicting the polypharmacological effects of small molecules across the kinome. By leveraging a novel meta-learning algorithm, KinomeMETA efficiently utilizes sparse activity data, enabling rapid generalization to new kinase tasks even with limited information. This significantly expands the repertoire of accurately predictable kinases to 661 wild-type and clinically-relevant mutant kinases, far exceeding existing methods. Additionally, KinomeMETA empowers users to customize models with their proprietary data for specific research needs. Case studies demonstrate its ability to discover new active compounds by quickly adapting to small dataset. Overall, KinomeMETA offers enhanced kinome virtual profiling capabilities and is positioned as a powerful tool for developing new kinase inhibitors and advancing kinase research. The KinomeMETA server is freely accessible without registration at https://kinomemeta.alphama.com.cn/., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Nonalcoholic fatty liver disease (NAFLD), along with its progressive forms nonalcoholic steatohepatitis (NASH) and NASH fibrosis, has emerged as a global health crisis. However, the absence of robust screening and risk evaluation tools contributes to the underdiagnosis of NAFLD. Herein, we reported a multichannel nanogenerator-assisted laser desorption/ionization mass spectrometry (LDI-MS) platform for early screening and risk evaluation of NAFLD. Specifically, titanium oxide nanosheets (TiNS) and covalent-organic framework nanosheets (COFNS) were employed as nanogenerators with excellent optical properties and exhibited efficient desorption/ionization during the LDI-MS process. Only ∼0.025 μL of serum without pretreatments and separation, serum metabolic fingerprints (SMFs) can be extracted within seconds. Notably, integrated SMFs from TiNS and COFNS significantly improved diagnostic performance and achieved the area under the curve (AUC) values of 1.000 with 100% sensitivity and 100% specificity for the validation sets of global diagnosis, early diagnosis, high-risk NASH, and NASH fibrosis evaluation. Additionally, four biomarker panels were identified, and their diagnostic AUC values were more than 0.944. Ultimately, key metabolic pathways indicating the change from simple NAFLD to high-risk NASH and NASH fibrosis were uncovered. This work provided a noninvasive and high-throughput screening and risk evaluation strategy for NAFLD healthcare management, thus contributing to the precise treatment of the NALFD.

As the key component in on-chip mode-division multiplexing systems, a compact silicon photonic-lantern mode (de)multiplexer is proposed and demonstrated using the shallow-etched tilt slot waveguide. The proposed six-mode (de)multiplexer is designed as a constant coupling length of 11.7 µm for each mode conversion and eliminates the adiabatic transition tapers for cascaded asymmetric directional couplers, which have an ultra-short total length of 69 µm. The measured peak insertion losses of the fabricated device for all mode channels are less than 1.2 dB, and the crosstalk is below -12.6 dB in a 60 nm waveband. Additionally, the simulation results indicate that the device has a good fabrication tolerance. The proposed mode (de)multiplexer is scalable and could provide a feasible solution for the dense integration of on-chip mode division multiplexing systems.

The advantages of small extracellular vesicles (sEV) in disease management have become increasingly prominent, with the main challenge lying in meeting the demands of large-scale extraction and high-throughput analysis, a crucial aspect in the realm of precision medicine. To overcome this challenge, an engineered on-plate aptamer array (16×24 spots) is developed for continuous scale-up microextraction of plasma sEV and their in situ metabolic analysis using mass spectrometry. With this integrated array strategy, metabolic profiles of sEV are acquired from the plasma of 274 antenatal or postpartum women, reducing analysis time by half (7.5 h) and sample volume by 95% (only 0.125 µL usage) compared to the traditional suspension method. Moreover, using machine learning algorithms on sEV metabolic profiles, a risk score system is constructed that accurately assesses the need for epidural analgesia during childbirth and the likelihood of post-administration fever. The system, based on admission samples, achieves an impressive 94% accuracy. Furthermore, post-administration fever can be identified from delivery samples, reaching an overall accuracy rate of 88%. This work offers real-time monitoring of the childbirth process that can provide timely guidance for maternal delivery, underscoring the significance of sEV detection in large-scale clinical samples for medicine innovation and advancement., (© 2024 Wiley‐VCH GmbH.)

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1-Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Soybean stem diameter (SD) and branch diameter (BD) are closely related traits, and genetic clarification of SD and BD is crucial for soybean breeding., Methods: SD and BD were genetically analyzed by a population of 363 RIL derived from the cross between Zhongdou41 (ZD41) and ZYD02878 using restricted two-stage multi-locus genome-wide association, inclusive composite interval mapping, and three-variance component multi-locus random SNP effect mixed linear modeling. Then candidate genes of major QTLs were selected and genetic selection model of SD and BD were constructed respectively., Results and Discussion: The results showed that SD and BD were significantly correlated (r = 0.74, P < 0.001). A total of 93 and 84 unique quantitative trait loci (QTL) were detected for SD and BD, respectively by three different methods. There were two and ten major QTLs for SD and BD, respectively, with phenotypic variance explained (PVE) by more than 10%. Within these loci, seven genes involved in the regulation of phytohormones (IAA and GA) and cell proliferation and showing extensive expression of shoot apical meristematic genes were selected as candidate genes. Genomic selection (GS) analysis showed that the trait-associated markers identified in this study reached 0.47-0.73 in terms of prediction accuracy, which was enhanced by 6.56-23.69% compared with genome-wide markers. These results clarify the genetic basis of SD and BD, which laid solid foundation in regulation gene cloning, and GS models constructed could be potentially applied in future breeding programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Yang, Chen, Liu, Zhang, Xiong, Yu, Yu, Wang, Song and Qiu.)

Deep-learning-based classification models are increasingly used for predicting molecular properties in drug development. However, traditional classification models using the Softmax function often give overconfident mispredictions for out-of-distribution samples, highlighting a critical lack of accurate uncertainty estimation. Such limitations can result in substantial costs and should be avoided during drug development. Inspired by advances in evidential deep learning and Posterior Network, we replaced the Softmax function with a normalizing flow to enhance the uncertainty estimation ability of the model in molecular property classification. The proposed strategy was evaluated across diverse scenarios, including simulated experiments based on a synthetic dataset, ADMET predictions, and ligand-based virtual screening. The results demonstrate that compared with the vanilla model, the proposed strategy effectively alleviates the problem of giving overconfident but incorrect predictions. Our findings support the promising application of evidential deep learning in drug development and offer a valuable framework for further research., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Exosomes, a growing focus for liquid biopsies, contain diverse molecular cargos. In particular, exosome metabolites with valuable information have exhibited great potential for improving the efficiency of liquid biopsies for addressing complex medical conditions. In this work, we design the directional growth of Ti-metal-organic frameworks on polar-functionalized magnetic particles. This design facilitates the rapid synergistic capture of exosomes with the assistance of an external magnetic field and additionally synergistically enhances the ionization of their metabolites during mass spectrometry detection. Benefiting from this dual synergistic effect, we identified three high-performance exosome metabolites through the differential comparison of a large number of serum samples from individuals with Alzheimer's disease (AD) and normal cognition. Notably, the accuracy of AD identification ranges from 93.18 to 100% using a single exosome metabolite and reaches a flawless 100% with three metabolites. These findings emphasize the transformative potential of this work to enhance the precision and reliability of AD diagnosis, ushering in a new era of improved diagnostic accuracy.

As a commercially available ingredient, the mono- and diglycerides (MDG) were widely used in a plant protein-based emulsion to provide effective, functional, emulsifying properties. The simultaneous addition of the MDG and pea protein isolate (PPI) was investigated by the methods of interfacial rheology and quantitative protein proteomics. The physicochemical quantitative analysis of the oil-water interface revealed an interfacial stability mechanism for the protein adsorption layer. For a low MDG concentration, the interfacial quantities of vicilin and albumin were increased, which could be attributed to the adsorption rate. For a high MDG concentration, both vicilin and albumin were displaced by MDG and desorbed from the interface, while legumin was more difficult to displace due to its slow adsorption and the complex structure of protein molecules. The protein molecules with the structural rearrangement interacted with MDG, exhibiting potential effects on the interfacial film structure. Combined with some nanotechnologies, the new comprehension of protein-emulsifier interactions may promote food delivery systems. The research aims to develop an in-depth analysis of interfacial proteins, and provide more innovative and tailored functionalities for the application of the plant protein emulsion.

Background: To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD)., Methods: A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women's Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free β-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups., Results: The AFP MoM and free β-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all P < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (≥35 years), increased free β-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group., Conclusions: Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (≥35 years) and hepatitis B carriers also increased maternal serum AFP significantly.

Objective: The aim of this work was to compare different local cutoff values (LCV) and inline cutoff values (ICV) in pregnant women in the second trimester at high risk for carrying fetuses with trisomy 21., Methods: This retrospective cohort study analyzed prenatal screening outcomes in pregnant women (n = 311,561). The receiver operating characteristic curve was used to evaluate the diagnostic significance of the trisomy 21 risk value, alpha-fetoprotein, and free beta human chorionic gonadotropin multiple of the median for predicting trisomy 21 risk. The cutoff value corresponding to the maximal Youden index was taken as the LCV. The screening efficiency of both cutoff values was compared., Results: The LCV cutoff value was lower than the ICV cutoff value (1/643 vs 1/270). The sensitivity increased by 19.80%, the positive predictive value decreased by 0.20%, and the false-positive rate increased by 6.50%., Conclusion: The LCV should be used to determine trisomy 21 risk, which can increase the detection rate of trisomy 21 in the second trimester., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To produce food-grade ice nucleators, a 3.77 kb ice nucleation gene ( iceE ) isolated from Pantoea agglomerans ( Erwinia herbicola ) was introduced into the Gram-positive microorganism Bacillus amyloliquefaciens for the first time. The differential scanning calorimetry (DSC) results indicated that recombined strain B9-INP was an effective ice nucleator for controlling the supercooling point of distilled water at low concentrations. In the presence of B9-INP cells, model food systems, including sucrose solution and sodium chloride solution, different pH solutions froze at a relatively high subzero temperature, thus increasing the supercooling point by 5.8~16.7 °C. Moreover, B9-INP also facilitated model and real food systems to freeze at -6 °C. This recombinant strain not only improved the freezing temperature of food systems but also shortened the total freezing time, thus saving energy and reducing consumption. The results suggest that B9-INP has great application potential in the frozen food industry.

Metastases to the thyroid gland (MTT) are uncommon in clinical practice. The ultrasound (US) features are easily confused with primary thyroid malignancy, Hashimoto's thyroiditis, and other thyroid diseases. Therefore, this study aimed to assess the role of US and analysis of prognosis of MTT. A total of 45 patients with MTT in the database between July 2009 and February 2022 at the Fujian Cancer Hospital were reviewed. US examinations were performed only on 20 patients, who were finally included in our study. Among the 20 patients, nine were male, and eleven were female. According to US characteristics, metastases to the thyroid gland were divided into nodular and diffuse types (17 and 3 cases, respectively). Three lesions (17.6%) had circumscribed margins, and 14 (82.4%) were uncircumscribed. Three lesions (17.6%) were regular in shape, and 14 (82.4%) were irregular. Nine metastases (52.9%) were a taller-than-wide shape, and eight (47.1%) were not a taller-than-wide shape. Ten lesions (58.8%) had rich vascularity, and seven (41.2%) had absence/not rich vascularity. The mean overall survival (OS) from the time of MTT diagnosis was 22 months (95% confidence interval: 5.95-38.05). The 1-, 3-, and 5-year OS after metastasis was 68.1%, 25.5%, and 17%, respectively. The prognosis of MTT was poor, which is closely related to the characteristics of the primary tumor and metastatic disease. The US findings and US-guided core needle biopsy may be useful in diagnosing MTT in patients with a history of the malignant tumors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Soft-template carbonized mesopores were developed for the purpose of enriching urinary exosomal glycans through organic-organic self-assembly using block copolymers and resol precursors. With a high surface area of 229 m 2 g -1 , a small pore size of 3.1 nm, and a significant amount of carbon that specifically interacts with oligosaccharides in glycans, this carbonized mesopore material exhibits high selectivity and low limits of detection (5 ng μL -1 ) towards glycans. Our analysis of complex urine samples from healthy volunteers and bladder carcinoma patients successfully profiled 48 and 56 exosomal glycans, respectively, and 16 of them were significantly changed. Moreover, one upregulated bisecting N-acetylglucosamine (GlcNAc)-type glycan with core fucose, two upregulated and two downregulated terminal-sialylated glycans were revealed to be linked to bladder carcinoma. This approach is of significant importance for understanding diseases that arise from protein glycosylation mutations, and it may contribute to the development of novel diagnostic and therapeutic strategies for bladder carcinoma., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Phototherapy is an effective strategy to control Candida albicans ( C. albicans ) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans . Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti- C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans -infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti- C. albicans efficacy.

The gradual increase in electromagnetic field (EMF) exposure levels poses a potential threat to human health and the normal operation of electronic systems. In order to know the environmental EMF conditions, measurements were carried out on roads of about 400 km in the urban area of Beijing, China. The measurement results show that the electric field strength of about 89% of the sampling points is within 3 V/m, and the electric field strength of other sampling points is relatively high. Combined with further spectrum analysis, it was found that the electric field strength of one road section exceeded the national standard limits. In addition, to help quickly identify the general condition of the environmental EMF, a set of procedures for mining the association rules between the electric field strength and population density and building density is proposed in this paper. The final association rules show that the electric field strength is usually lower than 1.5 V/m in areas with medium or lower population density and areas with low building density; the electric field strength in areas with extremely high population density and areas with high building density is usually 1.5-4 V/m; while the electric field strength higher than 4 V/m mainly occurs in areas with extremely high population density. It is recommended to focus on strengthening the monitoring of EMF in areas with extremely high population density, and at the same time continuously pay attention to the trend of the urban EMF levels, so as to achieve early warning and treatment of relevant risks., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Capsaicin, the principal spicy component of red pepper, shows numerous bioactivities these years. Based on the results of past studies, capsaicin may have potential effects on the treatment of functional dyspepsia (FD). However, most studies mainly investigate functional dyspepsia-treatment effects of capsaicin by discussing the relationship between capsaicin and transient receptor potential vanilloid type 1 (TRPV1). In fact, capsaicin may relieve the symptoms of FD in various ways. These effects involve desensitizing C nociceptive fibers, regulating kinds of neurotransmitters, counteracting viruses and inflammation, balancing the gut microbiota, inhibiting the secretion of gastric acid, and reducing oxidative stress damage. A full understanding of these mechanisms will help further development and utilization of capsaicin in food and medical fields., (© 2023 Wiley-VCH GmbH.)

With its well-documented toxicity, the use of doxorubicin (Dox) for cancer treatment requires trade-offs between safety and effectiveness. This limited use of Dox also hinders its functionality as an immunogenic cell death inducer, thus impeding its usefulness for immunotherapeutic applications. Here, we develop a biomimetic pseudonucleus nanoparticle (BPN-KP) by enclosing GC-rich DNA within erythrocyte membrane modified with a peptide to selectively target healthy tissue. By localizing treatment to organs susceptible to Dox-mediated toxicity, BPN-KP acts as a decoy that prevents the drug from intercalating into the nuclei of healthy cells. This results in significantly increased tolerance to Dox, thereby enabling the delivery of high drug doses into tumor tissue without detectable toxicity. By lessening the leukodepletive effects normally associated with chemotherapy, dramatic immune activation within the tumor microenvironment was also observed after treatment. In three different murine tumor models, high-dose Dox with BPN-KP pretreatment resulted in significantly prolonged survival, particularly when combined with immune checkpoint blockade therapy. Overall, this study demonstrates how targeted detoxification using biomimetic nanotechnology can help to unlock the full potential of traditional chemotherapeutics.

The characterization and dynamics of protein structures upon adsorption at the air/water interface are important for understanding the mechanism of the foamability of proteins. Hydrogen-deuterium exchange, coupled with mass spectrometry (HDX-MS), is an advantageous technique for providing conformational information for proteins. In this work, an air/water interface, HDX-MS, for the adsorbed proteins at the interface was developed. The model protein bovine serum albumin (BSA) was deuterium-labeled at the air/water interface in situ for different predetermined times (10 min and 4 h), and then the resulting mass shifts were analyzed by MS. The results indicated that peptides 54-63, 227-236, and 355-366 of BSA might be involved in the adsorption to the air/water interface. Moreover, the residues L55, H63, R232, A233, L234, K235, A236, R359, and V366 of these peptides might interact with the air/water interface through hydrophobic and electrostatic interactions. Meanwhile, the results showed that conformational changes of peptides 54-63, 227-236, and 355-366 could lead to structural changes in their surrounding peptides, 204-208 and 349-354, which could cause the reduction of the content of helical structures in the rearrangement process of interfacial proteins. Therefore, our air/water interface HDX-MS method could provide new and meaningful insights into the spatial conformational changes of proteins at the air/water interface, which could help us to further understand the mechanism of protein foaming properties.

In the present study, the effects of magnesium ions on the conformational changes of the deuterated 1,2-dimyristoyl- sn -glycero-3-phosphoethanolamine (D 54 -DMPE) monolayer were elucidated by frequency-resolved sum frequency generation vibrational spectroscopy (SFG-VS) and surface pressure-area isotherm measurements. It is found that the tilt angles of the methyl in tail groups decrease, while the tilt angles of the phosphate and methylene in head groups increase during the compression of the DMPE monolayers at both the air/water interface and the air/MgCl 2 solution interfaces. It is also shown that the tilt angle of the methyl in the tail groups slightly decreases, while the tilt angles of the phosphate and methylene in the head groups significantly increase as the MgCl 2 concentration increases from 0 to 1.0 M. These results indicate that both the tail groups and the head groups of the DMPE molecules become closer to the surface normal, as the MgCl 2 concentration increases in the subphase.

Biochar and earthworms can accelerate di-(2-ethylhexyl) phthalate (DEHP) degradation in soils. However, little is known regarding the effect of biochar-assisted vermicomposting on soil DEHP degradation and the underlying mechanisms. Therefore, the present study investigated DEHP degradation performance and bacterial community changes in farmland soils using earthworms, biochar, or their combination. Biochar-assisted vermicomposting significantly improved DEHP degradation through initial physical adsorption on biochar and subsequent rapid biodegradation in the soil, earthworm gut, and charosphere. Burkholderiaceae, Pseudomonadaceae, and Flavobacteriaceae were the potential DEHP degraders and were enriched in biochar-assisted vermicomposting. In particularly, Burkholderiaceae and Sphingomonadaceae were enriched in the earthworm gut and charosphere, possibly explaining the mechanism of accelerated DEHP degradation in biochar-assisted vermicomposting. Soil pH, soil organic matter, and humus (humic acid, fulvic acid, and humin) increased by earthworms or biochar enhanced DEHP degradation. These findings imply that biochar-assisted vermicomposting enhances DEHP removal not only through rapid physical sorption but also through the improvement of soil physicochemical characteristics and promotion of degraders in the soil, earthworm gut, and charosphere. Overall, biochar-assisted vermicomposting is a suitable method for the remediation of organic-contaminated farmland soils., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the oral health knowledge of elementary school teachers and assess their attitude towards oral health education in Zunyi., Methods: A total of 636 teachers from 10 primary schools in Zunyi were selected by stratified sampling, and their general information, oral health care habits, results of oral health knowledge questionnaire, and attitude towards oral health and oral health education were investigated. Data were statistically analyzed using SPSS 21.0., Results: A total of 614 teachers answered the questionnaires. Only 8.8% brush their teeth for more than three minutes, 23.8% brush their teeth horizontally, 64.7% do not performteeth cleaning, and 78.2% do not use floss. Teachers have a weak understanding that six-year teeth are permanent, that pit and fissure sealing could prevent dental caries, and that dental floss could remove dental plaque. However, their attitude towards oral health and oral health education was found to be good., Conclusions: Schools could improve teachers' oral health know-ledge by organizing training and other activities. Teachers could also play an active role in leading and cultivating school-age children to establish good oral habits.

Introduction: Nomograms of prognosis in patients with a history of cardiac arrest (CA) have been established. However, there are some shortcomings and interferences in their clinical application., Objectives: Our study aimed at developing a utility nomogram to predict the risk of in‑hospital death in post‑CA patients., Patients and Methods: We retrospectively extracted data from the MIMIC‑IV database. The least absolute shrinkage and selection operator logistic regression and multivariable logistic regression were used to investigate independent risk factors. A nomogram defined as a prediction model was established for these independent risk factors. The model performance was measured by examining discrimination (area under the receiver operating characteristic curve [AUC]), calibration (calibration curve analysis), and utility (decision curve analysis [DCA])., Results: A total of 1724 post‑CA patients were enrolled in the study. Of those, 788 survived and 936 died. The incidence of in‑hospital death was 54.3%. In this nomogram, the predictors included age, malignant cancer, bicarbonate, blood urea nitrogen, sodium, heart rate, respiratory rate, temperature, SPO2, norepinephrine prescription, and lactate level. The internally validated nomogram showed good discrimination (AUC 0.801; 95% CI, 0.775-0.835). The calibration curve analysis and DCA confirmed that this prediction model can be clinically useful., Conclusions: We established a risk prediction model based on the admission characteristics to accurately predict the clinical outcome in post‑CA patients. The nomogram might help with the risk identification and individual clinical interventions.

Objective: The aim of this research was to determine whether systemic inflammatory indicators, including aggregate index of systemic inflammation (AISI), neutrophils lymphocyte to platelet ratio (NLPR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), are related to bone mineral density (BMD) in perimenopausal and postmenopausal women., Methods: One hundred and eighty-one perimenopausal and 390 postmenopausal women were enrolled in this cross-sectional study. Continuous variables by analysis of variance and Kruskal Wallis test for comparing the clinical characteristics. Linear regression analysis was conducted to investigate the associations between inflammatory indicators with BMD. The comparison between the subgroups was performed using the nonparametric test and the T -test., Results: AISI, NLPR, SII, and SIRI quartile values were inversely associated with BMD in menopausal women ( P = 0.021; P = 0.047; P < 0.001; P < 0.001, respectively). After adjusting for confounding factors, four inflammatory indicators remained significantly associated with BMD (all P for trend <0.001). Analysis according to menopausal status demonstrated that AISI, SII, and SIRI were significantly correlated with mean femoral neck BMD in postmenopausal women ( P for trend = 0.015, 0.004, and 0.001), but not significantly associated with BMD in perimenopausal women ( P for trend = 0.248, 0.054, and 0.352) after adjustment for covariates., Conclusion: The quartile values of AISI, SII, and SIRI were inversely associated with BMD in postmenopausal women, following adjustment for individual variables, hormone profiles and glucolipid metabolism profiles. AISI, SII, and SIRI have potential to be important tools for screening and prevention of bone loss in menopausal women in future clinical practice., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Chen et al.)

Objectives: To present a method combining ultrasound (US) and contrast-enhanced ultrasound (CEUS) features for differential diagnosis of cervical tuberculous lymphadenitis (CTL) and primary lymphoma., Methods: A total of 155 patients with CTL (n = 49) and lymphoma (n = 106) who underwent US and CEUS were retrospectively included. The features extracted from US and CEUS and the significant clinical data were created three models using the least absolute shrinkage and selection operator and logistic regression analysis. The diagnostic performance of the models was assessed using the area under the curve (AUC)., Results: The combined model outperformed US model and CEUS model in distinguish CTL from lymphoma achieved favorable performances in training set and validation set with AUCs of 0.958 and 0.946 as well as high accuracies (91.7% and 87.2%), sensitivities (95.9% and 84.4%) and specificities (82.4% and 93.3%). Delong's test showed that among the three models, combined model was significantly different from the other two models in training set (p = 0.011 and 0.029, respectively) and validation set (p = 0.018 and 0.001, respectively)., Conclusions: A combination of US and CEUS achieved good diagnostic performance in differentiating lymphoma and CTL, which might aid in clinical decision-making.

Objective: To observe the clinical characteristics of mild and common COVID-19 patients infected with the Omicron variant, and to analyze related factors affecting the time to negative conversion of viral nucleic acid detection., Methods: Clinical data of 1781 patients with coronavirus disease 2019 (COVID-19) admitted to a cabin hospital in Shanghai from April 12 to May 26, 2022, were retrospectively analyzed, including age, gender, height, weight, clinical symptoms, comorbid diseases, COVID-19 vaccination, treatment, and nucleic acid negative conversion time. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of nucleic acid negative conversion time., Results: Among the 1781 patients, 995 were male and 786 were female, with a median age of 39 (30, 52) years. There were 727 patients (40.8%) with overweight and obesity [body mass index (BMI) > 24 kg/cm 2 ) and 413 patients (23.2%) had comorbid diseases. 205 cases (11.5%) were not vaccinated while 1576 cases were vaccinated. There were 1233 cases (69.2%) with one or more symptoms. The main clinical symptoms were cough (60.3%), expectoration (50.4%) and fever (36.9%). 1444 cases (81.0%) were treated with Chinese medicine, 78 cases (4.4%) were treated with western medicine, 14 cases (0.8%) were treated with integrated Chinese and western medicine, and 245 cases (13.8%) did not receive any medical treatment. All patients improved and were discharged. The median nucleic acid negative conversion time was 10.3 (7.4, 12.4) d. Univariate and multivariate analysis showed that, age ≥ 60 years ( OR ＝1.537, 95% CI : 1.116 - 2.115, P <0.01), BMI > 24 kg/cm 2 ( OR ＝1.344, 95% CI : 1.106 - 1.634, P <0.01 ) and hypertension ( OR ＝1.518, 95% CI : 1.094 - 2.106, P <0.05) were independent risk factors for prolonged nucleic acid negative conversion. COVID-19 vaccination ( OR =0.548, 95% CI : 0.398 - 0.755, P <0.01) was a protective factor, that is, vaccination shortened the time for the nucleic acid test to become negative., Conclusions: The symptoms of the Omicron variant infection were relatively mild and occult. Age ≥ 60 years old, comorbid hypertension, no vaccination and BMI > 24 kg/cm 2 are independent influencing factors for prolonged nucleic acid negative conversion.

Pre-eclampsia (PE) is a complicated pregnancy-specific disease and is considered the primary reason for maternal and foetal mortality and morbidity. PE has a multifactorial pathogenesis but the causes of PE remain unclear. The functions of trophoblasts, including differentiation, proliferation, migration, invasion and apoptosis, are essential for successful pregnancy. During the early stages of placental development, trophoblasts are strictly regulated by several molecular pathways; however, an imbalance of these molecular pathways can lead to severe placental lesions and pregnancy complications. Certain microRNAs (miRs) are abnormally expressed in PE, with several miRs involved in the regulation of pregnancy-associated genes. The present review discusses the miRs regulating trophoblast function, how they affect the pathogenesis of PE and evaluating the possibility of miRs in screening, diagnosis and treatment of PE., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ning et al.)

Objective: To evaluate the effectiveness of alpha-fetoprotein variants (AFP-L2, AFP-L3) in fetal screening for Trisomy 18 in place of alpha fetoprotein (AFP)., Methods: A retrospective case-control study was conducted. Collectively, 39 pregnant women bearing Trisomy 18 fetuses and 48 pregnant women with clinically normal and healthy fetuses were included. The serum AFP-L2 and AFP-L3 concentrations were detected by enzyme-linked immunosorbent assays. The likelihood ratio method and Python software were used to construct the risk model with AFP, free β-hCG, AFP-L2, and AFP-L3 to predict Trisomy 18. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value, while the area under the curve (AUC) was used to assess the screening performance of AFP-L2 and AFP-L3 for fetal Trisomy 18., Results: Compared to values observed for the control group, AFP-L2 and AFP-L3 concentrations which were significantly higher (both p < .001) in pregnant women with Trisomy 18 fetuses were 7.95 ± 3.57 ng/mL and 2.53 ± 1.80 ng/mL, respectively. Comparisons across multiple modeling methods showed that the highest AUC of screened Trisomy 18 fetuses (0.992, 0.986, and 0.976) was yielded by AFP-L2 + AFP-L3 + free β-hCG, AFP-L2 + free β-hCG, and AFP-L3 + free β-hCG, with a sensitivity of 1.000 indicated in both instances. In different modeling methods, the order of AUC values was AFP-L2 + AFP-L3 + free β-hCG > AFP-L2 + free β-hCG > AFP-L3 + free β-hCG > AFP + free β-hCG., Conclusions: AFP-L2 and AFP-L3 showed higher sensitivity and specificity as substitutes for AFP in screening Trisomy 18. These two markers indeed improved the screening efficiency and reduced the false positive rate, when compared with AFP only.

Purpose: Poly(lactic- co -glycolic) acid (PLGA) nanoparticles coated with the membrane of red blood cells (RBC-NP) have been applied in various biomedical fields. Despite the well-documented great biocompatibility, the potential toxicity of RBC-NP on maternal mice or their developing fetuses during pregnancy, or juvenile mice post-birth, remains unclear, which warrants a systematic evaluation., Methods: We fabricate an RBC-NP with approximately 50 nm in diameter (RBC-NP-50). Upon RBC-NP-50, pregnant mice are intravenously injected with this nanoparticle either at a single high dose of 400 mg/kg (1HD) or a low dose of 200 mg/kg for 3 times (3LD). Afterwards, the biocompatible assessments are performed at 48 h after the final injection or 21 d post-birth/partum both on maternal and fetal/juvenile mice., Results: RBC-NP-50 is capable of accumulating in the placenta and then passing through the blood-fetal barrier (BFB) into the fetus. On 48 h after RBC-NP-50 exposure, no significant dose-dependent toxicity is observed in maternal mice including blood biochemistry, inflammatory factors, progesterone level, histological analysis, etc, whereas fetal brains reveal remarkable differentially expressed genes analyzed by transcriptome sequencing. On 21 d post-birth, those genes' expression in juvenile mice is alleviated, along with negligible differences in behavioral evaluations including surface righting test, negative geotaxis test, cliff avoidance test, and olfactory orientation test., Conclusion: These results indicate that RBC-NP is considered to be generally safe and biocompatible both for maternal mice and fetus during pregnancy, and for the subsequent juvenile mice post-birth, although future studies will need to examine higher dosage or longer-term measurements., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Chen et al.)

Objective: To investigate the efficacy of oral letrozole (LE) starting on day 3 or 5 of the menstrual cycle in patients with polycystic ovary syndrome (PCOS)., Design: Retrospective cohort study., Setting: Reproductive Endocrinology Department of Hangzhou Women's Hospital., Methods: In this retrospective analysis, we analyzed patients who received oral LE for ovulation induction (OI) at the Hangzhou Women's Hospital from January 2016 to January 2021. In total, 539 PCOS patients with fertility requirements were classified into the D3 group and D5 group according to the different starting times of oral LE, that is, from the 3rd or 5th day of the menstrual cycle or LE is taken orally for 5 days starting on day 3 or 5 of progesterone withdrawal bleeding. Treatment started with one tablet (LE 2.5 mg), continue the regimen from the previous cycle in non-responders and continued until pregnancy or for up to three ovulatory cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The primary outcome was to compare ovulation rates, conception rates, live birth rates, pregnancy complications, and pregnancy outcomes at different initiation times., Results: Women who started LE on the 5th day of their menstrual cycle had more cumulative conception rates than those who started LE on the 3rd day(173 of 228[75.9%] vs . 201 of 311[64.6%], P= 0.005; rate ratio for conception, 1.174; 95% confidence interval,1.052 to 1.311) without significant differences in overall live birth rate, though there were 142 of 228[62.3%] in the D5 group versus 172 of 311[55.3%] in the D3 group (P= 0.105). The median (IQR) endometrial thickness was significantly (P = 0.013) greater during the D5 group treatment compared to the D3 group, which may be related to higher conception and clinical pregnancy rates. The median (IQR) maximum follicle diameter was not statistically (P = 0.073) different between the two groups. The cumulative ovulation per cycle rate was higher with D5 than with D3 (287 of 405 treatment cycles [70.9%] vs . 388 of 640 treatment cycles [60.6%], P=0.001). There were no significant between-group differences in pregnancy loss (31 of 173 conceptions in the D5 group [17.9%] and 29 of 201 conceptions in the D3 group [14.4%]) or multiples pregnancy (8.2% and 10.5%, respectively). Rates of other adverse events during pregnancy were similar in the two treatment groups., Conclusion: As compared with D3 group, D5 group was associated with higher ovulation and conception rates, shorter time-to-pregnancy among infertile women with the PCOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Ye, Gao, Chen, Jin and Zhang.)

Germination of soybean seed is the imminent vital process after sowing. The status of plumular axis and radicle determine whether soybean seed can emerge normally. Epicotyl, an organ between cotyledons and first functional leaves, is essential for soybean seed germination, seedling growth and early morphogenesis. Epicotyl length (EL) is a quantitative trait controlled by multiple genes/QTLs. Here, the present study analyzes the phenotypic diversity and genetic basis of EL using 951 soybean improved cultivars and landraces from Asia, America, Europe and Africa. 3VmrMLM was used to analyze the associations between EL in 2016 and 2020 and 1,639,846 SNPs for the identification of QTNs and QTN-by-environment interactions (QEIs)".A total of 180 QTNs and QEIs associated with EL were detected. Among them, 74 QTNs (ELS&#95;Q) and 16 QEIs (ELS&#95;QE) were identified to be associated with ELS (epicotyl length of single plant emergence), and 60 QTNs (ELT&#95;Q) and 30 QEIs (ELT&#95;QE) were identified to be associated with ELT (epicotyl length of three seedlings). Based on transcript abundance analysis, GO (Gene Ontology) enrichment and haplotype analysis, ten candidate genes were predicted within nine genic SNPs located in introns, upstream or downstream, which were supposed to be directly or indirectly involved in the process of seed germination and seedling development., Of 10 candidate genes, two of them (Glyma.04G122400 and Glyma.18G183600) could possibly affect epicotyl length elongation. These results indicate the genetic basis of EL and provides a valuable basis for specific functional studies of epicotyl traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hong, Li, Chen, Wang, Wang, Guo, Gao, Ren, Yuan, Han and Qiu.)

Background: Insulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH)., Methods: A retrospective case-control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st-4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay., Results: A significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st-4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P < 0.001). After adjusting for age, body mass index, metabolic indices, and serum levels of oestradiol and total testosterone, AMH levels remained positively and significantly associated with INSL5 levels (P for trend < 0.001). The diagnostic value of AMH was better than that of INSL5., Conclusions: INSL5 and AMH levels were significantly correlated and elevated in women with PCOS. INSL5 and AMH might be associated with increased androgen secretion and chronic anovulation in PCOS., (© 2022. The Author(s).)

Objective: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with thyroglobulin (Tg) levels in fine-needle aspirates (FNA) washout fluid (FNA-Tg) in diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC) patients., Methods: Data from 190 LNs in 167 patients suspected of metastasis from the US between November 2018 and September 2020 were included. All subjects underwent FNA, CEUS, and FNA-Tg examinations. The final outcomes were confirmed by histopathological or cytological examination or follow-up imaging. Data were analyzed using the Wilcoxon rank-sum or chi-squared test. The diagnostic efficacy of FNA, CEUS, and FNA-Tg in diagnosing LNs was compared., Results: A cutoff value of 6.15 ng/ml (AUC 0.925, 95% confidence interval (CI) 0.885-0.966) successfully identified metastatic LNs. FNA missed 58 LN metastases, of these, 94.8% (55/58) were correctly diagnosed using the combination of CEUS and FNA-Tg. FNA-Tg showed higher sensitivity (90.2%), NPV (86.1%) and accuracy (88.9%) than either FNA (48.2, 57.4 and 69.5%, respectively) or CEUS (82.1, 67.7 and 70.5%, respectively) alone. The combination of CEUS, FNA and FNA-Tg resulted in maximal sensitivity (100%) and NPV (100%) but reduced specificity (51.3%) and overall diagnostic accuracy (80.0%). After adding FNA-Tg to discordant samples between CEUS and FNA, 81.9% of LNs (77/94) were correctly diagnosed., Conclusions: The combination of FNA, FNA-Tg and CEUS was found to be a promising imaging tool in detecting metastatic LNs in PTC patients., (© 2021 American Institute of Ultrasound in Medicine.)