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Jie Li,1,2 Xinyu Nan,1 Yixuan Ma,3 Zhen Wang,4 Hui Fang1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, 063000, People’s Republic of China; 3Graduate School, Hebei North University, Zhangjiakou, 075000, People’s Republic of China; 4Department of Orthopedics, Handan First Hospital, Handan, 056000, People’s Republic of ChinaCorrespondence: Hui Fang, Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, 063000, People’s Republic of China, Tel +86 13831581838, Email fanghui2818@126.comAbstract: Diabetes mellitus is a metabolic disease characterized by elevated blood glucose due to a deficiency of insulin secretion and/or action. Long-term poor blood glucose control may lead to chronic damage and dysfunction of the heart, kidneys, eyes, and other organs. Therefore, it is important to develop treatments for diabetes and its chronic complications. Fingolimod is a structural sphingosine analogue and sphingosine-1-phosphate receptor modulator currently used for the treatment of relapsing-remitting multiple sclerosis. Several studies have shown that it has beneficial effects on the improvement of diabetes and its chronic complications. This paper reviews the therapeutic potential of Fingolimod in diabetes and its chronic complications, aiming to further guide future treatment strategies.Keywords: fingolimod, diabetes mellitus, diabetes-related complications, treatment

Xiangzhen Nan, Jijie Yu, Yafeng Liang, Pengcheng Lou, Guoquan Pan Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Guoquan Pan, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86-13806882183, Email 81801800@163.comObjective: The aim of this study was to explore the value of applying different sampling methods combined with metagenomic next-generation sequencing (mNGS) to detect pathogens in children with severe pneumonia on mechanical ventilation.Methods: Forty children with severe pneumonia on mechanical ventilation were selected, and routine endotracheal suctioning and bronchoalveolar lavage fluid (BALF) sampling methods were performed. The diagnostic efficacy of different sampling methods combined with mNGS versus traditional etiological pathogen detection strategies was compared.Results: The positive rate of mNGS pathogen detection after routine endotracheal suctioning and BALF sampling was higher than that of traditional etiological detection strategies (P < 0.05). There was no significant difference in the positive rates of pathogen detection by routine endotracheal suctioning + mNGS and BALF + mNGS (P > 0.05).Conclusion: Compared with traditional etiological detection strategies, mNGS is more efficient for diagnosing pathogens. In clinical practice, an appropriate sampling method should be selected for mNGS-based detection according to the condition of the patient. These findings could be of great importance in the diagnosis and treatment of severe pneumonia.Keywords: sampling method, next-generation sequencing, severe pneumonia, metagenomics, mechanical ventilation

[This corrects the article DOI: 10.1371/journal.pone.0275642.].

Abstract Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type‐5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate‐cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital‐based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory‐approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline‐recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory‐approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra‐patient efficacy of the two treatment approaches.

Xiangzhen Nan, Yean Zhang, Nana Su, Lei Yang, Guoquan Pan Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Guoquan Pan, Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email gq_pan@163.comPurpose: This study aimed to analyze the application value of metagenomic next-generation sequencing (mNGS) as a basis for the proper adjustment of the clinical treatment of bloodstream infections (BSIs) in pediatric patients under intensive care.Methods: We retrospectively enrolled 46 pediatric patients with clinically diagnosed BSIs who were hospitalized in the pediatric intensive care unit of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University from June 2018 to July 2021. Blood samples were collected for cultivation and for mNGS detection of pathogens.Results: Among the 46 children, the average turnaround time for blood culture tests was 3.2 days, and the results revealed pathogens in three children (6.5%). The average turnaround time for mNGS was 2.2 days, and pathogens were found in 30 children (65.2%). The difference in positivity rates between blood culture and mNGS was significant (p< 0.05). Blood culture tests found three pathogens, while mNGS identified 28 pathogens, indicating that mNGS detected significantly more types of pathogens than the traditional diagnostic method for pathogenic microorganisms. In some children, more than one pathogen was detected.Conclusion: mNGS can help identify pathogenic microorganisms associated with BSI in some pediatric patients under intensive care.Keywords: pediatric intensive care unit, bloodstream infection, next-generation sequencing, metagenomics

Wenjia Lai,1,* Dan Li,2,3,* Qingsong Wang,4 Xiaohui Nan,2,3 Zhichu Xiang,2,3 Yan Ma,5 Ying Liu,2 Jiankui Chen,6 Jiesheng Tian,7 Qiaojun Fang2,3 1CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, People’s Republic of China; 2CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, People’s Republic of China; 3University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China; 4State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, People’s Republic of China; 5Aviation Service Department, Yantai Engineering & Technology College, Yantai 264000, People’s Republic of China; 6Clinical Laboratory, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, People’s Republic of China; 7State Key Laboratories for Agrobiotechnology and College of Biological Sciences, China Agricultural University, Beijing 100193, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiesheng TianState Key Laboratories for Agrobiotechnology and College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People’s Republic of ChinaTel +86 10-62731440Email tianhome@cau.edu.cn Qiaojun FangCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, No. 11 ZhongGuanCun Beiyitiao, Haidian District, Beijing 100190, People’s Republic of ChinaTel +86 10-82545562Email fangqj@nanoctr.cnPurpose: It is well known that when exposed to human blood plasma, nanoparticles are predominantly coated by a layer of proteins, forming a corona that will mediate the subsequent cell interactions. Magnetosomes are protein-rich membrane nanoparticles which are synthesized by magnetic bacteria; these have gained a lot of attention owing to their unique magnetic and biochemical characteristics. Nevertheless, whether bacterial magnetosomes have a corona after interacting with the plasma, and how such a corona affects nanoparticle–cell interactions is yet to be elucidated. The aim of this study was to characterize corona formation around a bacterial magnetosome and to assess the functional consequences.Methods: Magnetosomes were isolated from the magnetotactic bacteria, M. gryphiswaldense (MSR-1). Size, morphology, and zeta potential were measured by transmission electron microscopy and dynamic light scattering. A quantitative characterization of plasma corona proteins was performed using LC-MS/MS. Protein absorption was further examined by circular dichroism and the effect of the corona on cellular uptake was investigated by microscopy and spectroscopy.Results: Various serum proteins were found to be selectively adsorbed on the surface of the bacterial magnetosomes following plasma exposure, forming a corona. Compared to the pristine magnetosomes, the acquired corona promoted efficient cellular uptake by human vascular endothelial cells. Using a protein-interaction prediction method, we identified cell surface receptors that could potentially associate with abundant corona components. Of these, one abundant corona protein, ApoE, may be responsible for internalization of the magnetosome-corona complex through LDL receptor-mediated internalization.Conclusion: Our findings provide clues as to the physiological response to magnetosomes and also reveal the corona composition of this membrane-coated nanomaterial after exposure to blood plasma.Keywords: LC-MS/MS, cellular interaction, cellular uptake, biogenic magnetic nanoparticle

Smart polymers as ideal drug nanocarriers have attracted much attention due to the effective drug delivery, internalization and release once triggered by intracellular stimuli, as well as reduced cytotoxicity. We here reported the anionic micelle consisting of copolymer (PEG-b-PAsp) and a PBE (Phenylboronic Ester) group grafted, which can achieve fast response to intracellular ROS and enhanced anti-tumor activity. With this, PEG-b-PAsp-g-PBE/DOX system showed better tumor growth inhibition when studied on HeLa cell lines with high level of intracellular ROS and its subcutaneous tumor models. Additionally, the administration of PEG-b-PAsp-g-PBE/DOX did cause significantly lower systemic toxicity in comparison with free DOX. Hence, PEG-b-PAsp-g-PBE could be a highly efficient and safe nanocarrier to improve the efficacy of chemotherapeutic.

Background The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for UK older adults, but how age moderates effectiveness is unclear. Methods Three annual cohorts of primary-care patients aged≥65y from the Clinical Practice Research Datalink selected from 2003–5 created a natural experiment (n = 324,804), reflecting the staged introduction of the vaccine. The outcome was symptoms consistent with community-acquired pneumococcal pneumonia (CAP) requiring antibiotics or hospitalisation. We used the prior event rate ratio (PERR) approach to address bias from unmeasured confounders. Results Vaccinated patients had higher rates of CAP in the year before vaccination than their controls, indicating the potential for confounding bias. After adjustment for confounding using the prior event rate ratio (PERR) method, PPV23 was estimated to be effective against CAP for two years after vaccination in all age sub-groups with hazard ratios (95% confidence intervals) of 0.86 (0.80 to 0.93), 0.74 (0.65 to 0.85) and 0.65 (0.57 to 0.74) in patients aged 65–74, 75–79 and 80+ respectively in the 2005 cohort. Age moderated the effect of vaccination with predicted risk reductions of 8% at 65y and 29% at 80y. Conclusions PPV23 is moderately effective at reducing CAP among UK patients aged≥65y, in the two years after vaccination. Vaccine effectiveness is maintained, and may increase, in the oldest age groups in step with increasing susceptibility to CAP.

The corrosion behavior of Q345qNH steel and Q420qNH steel in simulated industrial atmospheric environment medium was studied by periodic immersion+infrared aging corrosion experiment. The results show that the corrosion type of both samples is uneven comprehensive corrosion, and the rust layer formed in the later stage of corrosion is relatively dense. But average corrosion rate of Q345qNH steel is always lower than that of Q420qNH steel, and the ratio of Iα‐FeOOH/Iγ‐FeOOH in rust layer is always higher. Compared with Q420qNH steel, Q345qNH steel has fewer surface pits but deeper local pits. The self‐corrosion potential of Q345qNH steel increases obviously, the resistance of the rust layer is larger, and protection to the matrix is stronger. This is because the formation of a large number of corrosion microcells induced by fine lamellar sorbite tissue that uneven distributed in Q420qNH steel, which increases the corrosion rate and makes corrosion uneven, while the larger pearlitic group in Q345qNH steel increases the local corrosion rate. However, the higher chromium/carbon ratio in Q345qNH steel promotes the conversion of lepidocrocite to goethite and inhibits the cathode reaction in the infrared drying stage, improving the density and stability of the rust layer. [ABSTRACT FROM AUTHOR]

Abstract Large‐scale wildfires can significantly reduce the air gap insulation resistance of high‐voltage transmission lines and cause chain tripping incidents. To assess the resilience of the power transmission system during wildfire, this paper proposes a resilience assessment framework for transmission system that considers the entire process of wildfire disaster. Firstly, a wildfire spread model, considering multiple influencing factors, is developed based on the cellular automaton. Based on the air gap breakdown mechanism during wildfires, the trip‐out probability of transmission lines is calculated, and various failure scenarios are obtained by using the Monte Carlo sampling. Secondly, considering the geographical location of failures, maintenance personnel schedules and restoration time, a power transmission system restoration model is established. Thus, a resilience assessment method for power transmission system during wildfire disasters is proposed. Finally, IEEE RTS‐79 transmission system is taken as an example to demonstrate the effectiveness of the proposed resilience assessment method. The results show that the proposed method can effectively calculate the wildfire spread tendency and transmission line's trip‐out probability. Furthermore, three typical resilience improvement measures are quantitatively analysed, which provides a quantifiable reference for the power sector to formulate prevention and recovery strategies for extreme wildfire disasters.

Abstract The study aims to identify potential drug targets for endometrial cancer (EC) subtypes through a Mendelian randomization (MR) approach, assessing their clinical relevance. We utilized genetic instruments for 4,907 plasma proteins from the deCODE Genetics study dataset, and data with EC (n = 12,906) from a genome-wide study (GWAS) meta-analysis in European populations for MR analyses. Complementary analyses included protein-protein interactions (PPI) network analysis, therapeutic efficacy evaluation, differential gene expression assessment, and prognosis evaluation. The expression levels of key drug targets were quantitatively measured at both the transcriptional and translational stages utilizing reverse transcription quantitative PCR (RT-qPCR) and immunohistochemistry (IHC). Additionally, we analyzed various clinicopathological features. Five drug targets for EC (CBR3, GSTO1, HHIP, IGF2R, and MMP10), seven for endometrioid subtypes (ACAP2, CBR3, GSTO1, HHIP, IGF2R, MMP10, and TLR2), and seven for non-endometrioid subtypes (CST3, DNAJB14, FSTL5, GMPR2, IFI16, MAPK9, and NEO1) were identified. Among these, IGF2R (OR = 1.165; 95% CI 1.067–1.272; p = 1.046 × 10− 2) and CST3 (OR = 0.523; 95% CI 0.339–0.804; p = 7.010 × 10− 3) were highlighted as key drug targets with causal evidence both at transcriptional and translational levels. This study preliminarily confirms that IGF2R and CST3 may serve as novel targets for the treatment of EC, providing a foundational reference for innovative clinical approaches to this disease.

Abstract Human pose estimation has a wide range of applications. Existing methods perform well in conventional domains, but there are certain defects when they are applied to sports activities. The first is lack of estimation of the extremity posture, making it impossible to comprehensively evaluate the movement posture; the second is insufficient occlusion handling. Therefore, we propose a human pose compensation network based on incremental learning, which obtains shared weights to extract detailed features under the premise of limited extremity training data. We propose a higher-order feature compensator (HOF-compensator) to embed the attributes of the extremity into the torso and limbs topology structure, building a complete higher-order feature. In addition, to improve the occlusion handling performance, we propose an occlusion feature enhancement attention mechanism (OFE-attention) that can identify occluded keypoints and enhance attention to occlusion areas. We design comparative experiments on three public datasets and a self-built sports dataset, achieving the highest mean accuracy among all comparative methods. In addition, we design a series of ablation analysis and visualization displays to verify that our method performs best in sports pose estimation.

Abstract In the calculation of reinforced concrete (RC) flat slabs with transverse reinforcement, punching shear resistance is one of the most critical factors. It is true that design provisions may be implemented, but they often result in significant biases and deviations from expectations. This study aims to present an optimized machine learning (ML) algorithm for estimating the punching shear resistance. Four machine learning (ML) algorithms (SVR, DT, RF, and XGBoost) with Bayesian optimization (BO) are presented in this paper to provide accurate predictions for flat slabs. The adoptability and optimization of the models are achieved through the analysis of a database of 337 test specimens with nine design parameters. Machine learning (ML) techniques are used to estimate punching shear resistance, which is compared with design provisions and equations relating to critical shear crack theory (CSCT). According to this study, Bayesian optimization is still capable of improving the performance of conventional machine learning algorithms, while the XGBoost-based model offers advanced capabilities. Predictions based on BO-XGBoost are in good agreement with actual values (MAE, RMSE, and R 2 are 0.09 MN, 0.14 MN, and 0.92, respectively) in test set. Following a detailed explanation using Shapley additive explanation (SHAP), a high-performance ML approach is used to investigate the predictive results. With the proposed optimized algorithms, it is possible to determine the punching shear resistance of flat slabs with transverse reinforcement during the preliminary stages of the construction.

Abstract Background There are differences in the research results regarding which edge design of occlusal veneers can achieve the best long-term success rate as a relatively new fixed prosthesis restoration method. Further research is needed. The three-dimensional finite element method was used to conduct stress analysis on occlusal veneers of maxillary first permanent molars with different thicknesses and margin preparation designs. The aim of this study was to provide mechanical research evidence and a reference for exploring standardized clinical protocols for the design of occlusal veneer restorations of maxillary first molars. Method A 3Shape (Intraoral Scanner) was used to scan the maxillary first molar teeth in vitro, after which 3D printing was carried out. Three different edge designs were applied to identical teeth: straight-beveled finishing line(SFL), chamfer finishing line(CFL), and standard cuspal inclination(SCI). Preparation was carried out with a thickness of 0.5 mm. Using the surface deformation feature, the occlusal veneer was thickened to 0.5 mm and 1.0 mm, and periodontal ligaments were added. They were then placed into the upper and lower jaws and dental arches. Finite element analysis was performed after applying bite force dispersion to the loading area on the mandible following dynamic contact. Results (1) As the thickness increased, the maximum Von Mises stress in the occlusal veneers SFL and CFL also increased, while the SCI exhibited the opposite trend. (2). The trend of the maximum Von Mises stress in the adhesive layer decrease gradually with increasing thickness of the occlusal veneer. The stresses of the SFL and CFL is concentrated primarily at the edge position below the functional cusp, resulting in relatively low adhesive stress. However, in the SCI group, the maximum stress at the edge of the adhesive layer exceeds the maximum shear strength of commonly used adhesives. Conclusions Under the experimental conditions, the mechanical properties of the maximum Von Mises stress in the SFL, CFL, and SCI occlusal veneers meet clinical needs. Incorporating the minimally invasive concept of tooth preservation, a thickness of 1.0 mm are optimal for glass ceramic occlusal veneers on maxillary first molars.

Abstract To solve the problems of difficulty in speed measurement and low accuracy of speed measurement of induction motor (IM) during fast starting, the electromagnetic field coupling circuit (EFCC) and open‐loop control of IM considering rapid speed change are proposed. First, the EFCC of IM is established through the stator circuit, air gap magnetic field circuit and rotor circuit, and the stator voltage and electromagnetic torque of the fast starting process are deduced from the air gap magnetic density on the basis of constant slip angular velocity, and then the open‐loop control method based on the EFCC is given. Finally, compared with the open‐loop control based on the TEC, the results of simulation and experiment show that the open‐loop control based on the EFCC can follow the acceleration starting more quickly and the starting current is smaller, which is conducive to reducing the cost of the drive.

Abstract Concerns have been raised about the sustainability of large-scale afforestation in semi-arid regions due to potential water constraints. This study investigated whether increased humidity in the semi-arid regions of northwest China could sustain the continued expansion of afforestation efforts. Using multi-source remote sensing data, we found that between 2012 to 2020, annual cumulative precipitation increased by 2.5 millimeters per year, while annual average carbon sequestration in afforested areas declined by 0.002 kilograms of carbon per square meter per year, indicating asynchronous trends. This disparity was primarily attributed to the trade-off between vegetation photosynthesis and transpiration in response to external water conditions, which led to a decline in the water use efficiency of afforested vegetation. The effect of water use efficiency on carbon sequestration was driven by gross primary productivity, rather than evapotranspiration. These findings underscore the importance of targeted afforestation in semi-arid regions, considering local water resource sustainability.

Abstract Background Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear. Methods We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC. Results Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration. Conclusions Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.

Abstract Introduction Concentrated Growth Factor (CGF), rich in CD34 + stem cells, is widely used in treatments for androgenetic alopecia and skin rejuvenation due to its immune-modulating properties. Psoriasis, a chronic inflammatory skin condition, presents significant treatment challenges, particularly for patients who cannot use biologics due to conditions such as cancer and lesions resistant to treatments. The potential of CGF in treating psoriasis is promising, given its broad immunoregulatory effects which confirmed in our previous androgenetic alopecia work. Methods We evaluated the impact of CGF on IL-17 levels in two contexts: patients treated for androgenetic alopecia and a psoriasis mouse model. Twelve patients received three monthly injections of CGF, with serum IL-17 levels measured before and after treatment. In the psoriasis mouse model, groups were treated with CGF, and outcomes were assessed using the Psoriasis Area and Severity Index (PASI), skin barrier scores, histological analysis, and RNA sequencing. Additionally, in vitro experiments applied CD34 + cells from CGF to keratinocytes to measure levels of TNF-α, IFN-γ, IL-23, and IL-17. Results In patients with androgenetic alopecia, three monthly CGF injections resulted in significantly reduced serum IL-17 levels. In the psoriatic mouse model, CGF-treated groups exhibited lower PASI scores and improved skin barrier scores compared to controls. Histological analysis revealed enhanced skin characteristics, while RNA sequencing demonstrated downregulated IL-17 and upregulated CD34 expression, as well as improved expression of barrier-related genes. In vitro, the application of CD34 + cells from CGF to keratinocytes led to a significant reduction in TNF-α, IFN-γ, IL-23, and IL-17 levels, indicating strong anti-inflammatory effects. A clinical case of a psoriasis patient unresponsive to IL-23 therapy (Guselkumab) showed significant improvement following CGF treatment. Conclusion These findings indicate that CGF could serve as an effective and versatile treatment for psoriasis, especially for patients who have already undergone biologic therapies but continue to experience resistant lesions.

Abstract In the rapidly evolving landscape of Industry 4.0, the complex computational tasks and the associated massive data volumes present substantial opportunities for advancements in machine learning at industry edges. Federated learning (FL), which is a variant of distributed machine learning for edge-cloud computing, presents itself as a persuasive resolution for these industrial edges, with its main objectives being the mitigation of privacy breaches and the resolution of data privacy concerns. However, traditional FL methodologies encounter difficulties in effectively overseeing extensive undertakings in Industry 4.0 as a result of challenges including wireless communications with high latency, substantial heterogeneity, and insufficient security protocols. As a consequence of these obstacles, blockchain technology has garnered acclaim for its secure, decentralized, and transparent data storage functionalities. A novel blockchain-enabled group federated learning (BGFL) framework designed specifically for wireless industrial edges is presented in this paper. By strategically dividing industrial devices into multiple groups, the BGFL framework simultaneously reduces the wireless traffic loads required for convergence and improves the accuracy of collaborative learning. Moreover, to optimize aggregation procedures and reduce communication resource utilization, the BGFL employs a hierarchical aggregation strategy that consists of both local and global aggregation off-chain and on-chain, respectively. The integration of a smart contract mechanism serves to fortify the security framework. The results of comparative experimental analyses demonstrate that the BGFL framework enhances the resilience of the learning framework and effectively reduces wireless communication latency. Thus, it offers a scalable and efficient solution for offloading tasks in edge-cloud computing environments.

The periodic immersion corrosion behavior and corrosion mechanism of Q420qNH steel weld, heat‐affected zone and plate sample in simulated industrial atmospheric medium were studied. The corrosion type of the three samples is the non‐uniform total corrosion, and the corrosion products at different stages are different. Ferric oxide and lepidocrocite (γ‐FeOOH) are generated in the immersion stage and the initial stage of infrared drying, respectively. However, lepidocrocite (γ‐FeOOH), ferrosoferric oxide (Fe3O4) and goethite (α‐FeOOH) generated in the later stage of infrared drying. The infrared drying process is conducive to the formation of goethite (α‐FeOOH). The corrosion rate of weld is always lower than that of plate, and the Iα‐FeOOH/Iγ‐FeOOH ratio of the weld is always higher than that of plate and heat‐affected zone sample. In the later stage of corrosion, the self‐corrosion current density of the three samples from small to large is weld, heat‐affected zone and plate, and self‐corrosion potential from large to small is weld, heat‐affected zone and plate. The resistance of the rust layer of the weld and heat‐affected zone sample is 1.81 times, 1.29 times of that of the plate, respectively. This is because the weld is composed of a large number of small angular grain boundary structures dominated by tiny acicular ferrite in the original austenite grain, which is conducive to the improvement of corrosion resistance. In addition, the higher chromium/carbon (Cr/C), copper and nickel elements of the weld can promote the conversion from lepidocrocite (γ‐FeOOH) to goethite (α‐FeOOH), and improve the density and stability of weld rust layer. [ABSTRACT FROM AUTHOR]

Abstract Background A dosimetric evaluation is still lacking in terms of clinical target volume (CTV) omission in stage III patients treated with 4D-CT Intensity-Modulated Radiation Therapy (IMRT). Methods 49 stage III NSCLC patients received 4D-CT IMRT were reviewed. Target volumes and organs at risk (OARs) were re-delineated. Four IMRT plans were conducted retrospectively to deliver different prescribed dose (74 Gy–60 Gy), and with or without CTV implementation. Dose and volume histogram (DVH) parameters were collected and compared. Results In the PTV-g 60 Gy plan (PTV-g refers to the PTV generated from the internal gross tumor volume), only 5 of 49 patients had the isodose ≥ 50 Gy line covering at least 95% of the PTV-c (PTV-c refers to the PTV generated from the internal CTV) volume. When the prescribed dose was elevated to 74 Gy to the PTV-g, 33 of 49 patients could have the isodose ≥ 50 Gy line covering at least 95% of the PTV-c volume. In terms of OARs protection, the SIB-IMRT plan showed the lowest value of V5, V20, and mean dose of lung, had the lowest V55 of esophagus, and the lowest estimated radiation doses to immune cells (EDIC). The V20, V30, and mean dose of heart was lower in the simultaneous integrated boost (SIB) IMRT (SIB-IMRT) plan than that of the PTV-c 60 Gy plan. Conclusions CTV omission was not suitable for stage III patients when the prescribed dose to PTV-g was 60 Gy in the era of 4D-CT IMRT. CTV omission plus high dose to PTV-g (74 Gy for example) warranted further exploration. The SIB-IMRT plan had the best protection to normal tissue including lymphocytes, and might be the optimal choice.

Abstract Aims To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective. Methods We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning. Results Four children—3 girls and 1 boy—with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%. Conclusion UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis.

Abstract Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Abstract The interaction between lattice vibrations and electrons plays a key role in various aspects of condensed matter physics — including electron hydrodynamics, strange metal behavior, and high-temperature superconductivity. In this study, we present systematic investigations using Raman scattering and angle-resolved photoemission spectroscopy (ARPES) to examine the phononic and electronic subsystems of the topological superconductor candidate 2M-WS2. Raman scattering exhibits an anomalous nonmonotonic temperature dependence of phonon linewidths, indicative of strong phonon–electron scattering over phonon–phonon scattering. The ARPES results demonstrate pronounced dispersion anomalies (kinks) at multiple binding energies within both bulk and topological surface states, indicating a robust and mode-selective coupling between the electronic states and various phonon modes. These experimental findings align with previous calculations of the Eliashberg function, providing a deeper understanding of the highest superconducting transition temperature observed in 2M-WS2 (8.8 K) among all transition metal dichalcogenides as induced by electron–phonon coupling. Furthermore, our results may offer valuable insights into other properties of 2M-WS2 and guide the search for high-temperature topological superconductors.

Abstract NOP2, a member of the NOL1/NOP2/SUN domain (NSUN) family, is responsible for catalyzing the posttranscriptional modification of RNA through 5-methylcytosine (m5C). Dysregulation of m5C modification has been linked to the pathogenesis of various malignant tumors. Herein, we investigated the expression of NOP2 in lung adenocarcinoma (LUAD) tissues and cells, and found that it was significantly upregulated. Moreover, lentivirus-mediated overexpression of NOP2 in vitro resulted in enhanced migration and invasion capabilities of lung cancer cells, while in vivo experiments demonstrated its ability to promote the growth and metastasis of xenograft tumors. In contrast, knockdown of NOP2 effectively inhibited the growth and metastasis of lung cancer cells. RNA-sequencing was conducted to ascertain the downstream targets of NOP2, and the findings revealed a significant upregulation in EZH2 mRNA expression upon overexpression of NOP2. Subsequent validation experiments demonstrated that NOP2 exerted an m5C-dependent influence on the stability of EZH2 mRNA. Additionally, our investigations revealed a co-regulatory relationship between NOP2 and the m5C reader protein ALYREF in modulating the stability of EZH2 mRNA. Notably, the NOP2/EZH2 axis facilitated the malignant phenotype of lung cancer cells by inducing epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, ChIP analysis proved that EZH2 counteracted the impact of NOP2 on the occupancy capacity of EZH2 and H3K27me3 in the promoter regions of E-cadherin, a gene crucial for regulating EMT. In a word, our research highlights the significant role of NOP2 in LUAD and offers novel mechanistic insights into the NOP2/ALYREF/EZH2 axis, which holds promise as a potential target for lung cancer therapy.

Xiao-tian Nan,1,&ast; Ma-chao Li,1,&ast; Tong-yang Xiao,2,&ast; Hai-can Liu,1,&ast; Shi-qiang Lin,3 Wei Wang,1 Cheng Qian,4 Hao Hang,1 Gui-lian Li,1 Xiu-qin Zhao,1 Kang-Lin Wan,1 Li-li Zhao1 1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 3College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, 100013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-li Zhao, Email zhaolili@icdc.cnObjective: To explore the association between the variant mutations within embB and ubiA, and the degree of ethambutol (EMB) resistance of Mycobacterium tuberculosis (M. tuberculosis) isolates.Methods: A total of 146 M. tuberculosis isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within embB and ubiA among these isolates were identified with DNA sequencing. Moreover, a multivariate regression model and a computer model were established to assess the effects of mutations on EMB resistance.Results: Our data showed that overall 100 isolates exhibited 28 mutated patterns within the sequenced embB and ubiA. Statistical analysis indicated that embB mutations Met306Val, Met306Ile, Gly406Ala, and Gln497Arg, were strongly associated with EMB resistance. Of these mutations, Met306Val and Gln497Arg were significantly associated with high-level EMB resistance. Almost all multiple mutations occurred in high-level EMB-resistant isolates. Although the mutation within ubiA accompanied with embB mutation presented exclusively in EMB-resistant isolates, four single ubiA mutations (Ala39Glu, Ser173Ala, Trp175Cys, and Val283Leu) leading to protein instability were observed in EMB-susceptible isolates.Conclusion: This study highlighted the complexity of EMB resistance. Some individual mutations and multiple mutations within embB and ubiA contributed to the different levels of EMB resistance.Keywords: ethambutol, multidrug-resistant tuberculosis, embB, ubiA, mutations, minimum inhibitory concentration

The assessment of urban renewal (UR) potential aims to prioritize areas for UR, which are essential for sustainable urban revitalization. However, conventional data sources often fall short in encompassing diverse urban characteristics in the evaluation process, such as urban three-dimensional (3D) building information and the intensity of human activities. To address this gap, this study integrated 3D building data and geographic data to create a comprehensive set of 28 indicators spanning four dimensions: natural environmental conditions, land use, socio-economic factors, and building conditions. These indicators take into account vertical dimensions, dynamic aspects, and fine-scale details. Leveraging the existing UR practices as a positive example, we established an UR potential assessment model at street block scale using Presence and Background Learning combined with extreme gradient boosting algorithms (PBLXGBoost). Our findings revealed that the highest accuracy in evaluating industrial UR potential was achieved in Shenzhen (Fpb_avg = 0.80, RMSEavg = 0.21), followed by residential and commercial UR potential assessments. Conversely, other type UR exhibit lower accuracy. Street blocks with significant UR potential are predominantly located in Bao’an, Longgang, and Longhua Districts. Furthermore, employing the SHAP model to elucidate the evaluation results uncovered intricate hierarchical, positive-negative, and overlapping relationships among various factors and different UR types, where geographic big data and 3D building information showed strong correlations. The methodology proposed in this study enables objective and precise assessments of UR potential, offering valuable support for UR practice and sustainable urban development.

Sandy beaches are at the frontline of resisting continuous sea level rise associated with anthropogenic climate change. However, accurate and comprehensive spatial information for monitoring, utilizing, and protecting sandy beaches is still lacking at the national or above scales. This study, for the first time, addresses this gap by collecting cloud-free, low-tide Sentinel-2 images in 2022 to map 10-m sandy beaches across China using the image classification method. We adopted the Support Vector Machine to derive the spatial distribution of sandy beaches, assess accuracy, and analyze spatial characteristics. Our results demonstrate the efficiency of the SVM model in mapping sandy beaches (User's accuracy: 96%, Kappa coefficient: 0.93). We identified 3,444 beaches in China, with a total length of 3,187.57 km, an average width of 69.93 meters, and a total area of 217.43 km², constituting 24.16% of the national coastline. Notably, Guangdong, Taiwan, and Hainan provinces are rich in beach resources, whereas Macao, Shanghai, Tianjin, and Jiangsu provinces have relatively fewer beach resources. Further, our results outperform the existing OpenStreetMap beach dataset. Our developed 10-m beach database is crucial for analyzing potential beach risks, uncovering socioeconomic values of beach resources, and promoting the sustainable coastal zone development in China.

Malignant tumors of the digestive system have had a notoriously dismal prognosis throughout history. Immunotherapy, radiotherapy, surgery, and chemotherapy are the primary therapeutic approaches for digestive system cancers. The rate of recurrence and metastasis, nevertheless, remains elevated. As one of the immunotherapies, chimeric antigen receptor T cell (CAR-T) therapy has demonstrated a promising antitumor effect in hematologic cancer. Despite undergoing numerous clinical trials, the ineffective antitumor effect and adverse effects of CAR-T cell therapy in the treatment of digestive system cancers continue to impede its clinical translation. It is necessary to surmount the restricted options for targeting proteins, the obstacles that impede CAR-T cell infiltration into solid tumors, and the limited survival time in vivo. We examined and summarized the developments, obstacles, and countermeasures associated with CAR-T therapy in digestive system cancers. Emphasis was placed on the regulatory functions of potential antigen targets, the tumor microenvironment, and immune evasion in CAR-T therapy. Thus, our analysis has furnished an all-encompassing comprehension of CAR-T cell therapy in digestive system cancers, which will generate tremendous enthusiasm for subsequent in-depth research into CAR-T-based therapies in digestive system cancers.

Accurate information on gross domestic product (GDP) is essential for better understanding the dynamics of regional economies and urbanization processes. Satellite based nighttime light datasets can well track GDP in urban areas, however, they are difficult to be used in suburban, rural and sparsely populated areas. Thus, this study explored the potential of GlobeLand30 and relief degree for improving the ability of VIIRS Nighttime Light data of GDP estimation. Firstly, we calculated the Moran’s Index (Moran’s I) to measure spatial auto-correlation of GDP. At provincial level, Moran’s I Index of GDP is 0.14, Z value is 2.29. While at the prefecture city level, it is 0.11 and 14.54, respectively. Then, we compared the results derived from geographically weighted regression (GWR) and OLS models (i.e., R2, root mean square error, corrected Akaike information criteria and residuals). Both models suggest that land cover information can significantly improve GDP estimation performance, and total nighttime light (TNL) is the most important economic indicator for estimating GDP. The coefficients of the GWR model for TNL at the provincial and prefecture levels are 1.75 and 1.19, respectively, which are significantly larger than the coefficients for other factors such as land cover and terrain undulation. In addition, the GWR model performed better than OLS model in GDP estimation at both provincial and prefecture levels, and prefecture-level models can better depict the spatial variation in detail. In provincial-level models, GWR could account for 93% of economic development, while OLS could only reflect 82%. Likewise, in prefecture-level models, R2 of GWR model improved almost 50% compared with that of OLS model.

Introduction With a precarious economic outlook and increasing income volatility in current times, understanding the association between negative income shock and health is crucial. However, few studies have examined such associations in developing countries. Using data from China, this study aimed to examine associations of both serial absolute income drops and relative income trajectory and mortality.Methods We included 4757 participants from the China Health and Nutrition Survey, a large prospective cohort study. Data between 1989 and 1997 were used to define income drops and relative income trajectories. We defined income drop as a decrease of ≥50% between two consecutive interviews and defined relative income trajectory using a latent class model. All-cause mortality between 2000 and 2015 was ascertained by participants’ family members.Results A total of 2066 (43.43%) experienced 1 income drop and 477 (10.03%) experienced ≥2 income drops. A total of 535 deaths occurred (incidence rate 8.88 per 1000 person-years). Income drops were associated with a greater risk of mortality after adjusting for baseline income, comorbidities, sociodemographic and behavioural factors (HR 1.42 (95% CI 1.04 to 1.93) for ≥2 income drops vs no income drop). The downshift in relative income was also associated with increased mortality risk (HR 3.61 (95% CI 1.45 to 8.96) for always low; HR 3.36 (95% CI 1.36 to 8.32) for decreasing; HR 2.92 (95% CI 1.14 to 7.51) for increasing vs always high relative income). The associations between income drops and mortality were observed only among individuals with low wealth and low household income.Conclusion In a large sample of the Chinese population with repeated income measurement and over 14 years of follow-up, both serial absolute income drops and a downward relative income trajectory were associated with higher risks of mortality in China. Priority should be given to policies aimed at enhancing resilience against serial income shocks and financial burdens.

Congenital portosystemic shunts (CPSS) are rare pediatric vascular malformations characterized by abnormal development of the portal vein, which is attributed to incomplete embryonic remodeling of the hepatic and surrounding vasculature. CPSS manifests in two main forms: intrahepatic and extrahepatic. This study details the management of a pediatric patient diagnosed with Congenital Intrahepatic Portosystemic Shunt (CIPS) who was referred to our institution. By using a computer-assisted surgical system, the right hepatectomy was successfully performed, guided by precise intraoperative navigation based on three-dimensional reconstructions of enhanced CT imagery. The patient exhibited a favorable postoperative recovery trajectory, with the absence of complications or recurrence throughout the monitoring period.

Abstract Severe cytokine release syndrome (sCRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)‐cell therapy. We designed a novel anti‐CD19 CAR (ssCART‐19) with a small hairpin RNA (shRNA) element to silence the interleukin‐6 (IL‐6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART‐19 with common CAR T‐cells (cCART‐19) in relapsed/refractory B‐cell acute lymphoblastic leukemia (r/r B‐ALL). Among 87 patients, 47 received ssCART‐19 and 40 received cCART‐19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART‐19 group versus 37.5% (15/40) in the cCART‐19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART‐19 group (all grade 1) compared to 15% (2/40) of the cCART‐19 group. Patients in the ssCART‐19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART‐19 and 85% (34/40) for cCART‐19 (p = 0.999). With a median follow‐up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART‐19 and 13.6% for cCART‐19 (p = 0.33). Median overall survival was 37.17 months for ssCART‐19 and 32.93 months for cCART‐19 (p = 0.40). Median progression‐free survival was 24.17 months for ssCART‐19 and 9.33 months for cCART‐19 (p = 0.23). These data support the safety and efficacy of ssCART‐19 for r/r B‐ALL, suggesting its potential as a promising therapy.

Biochar has been recognised as an efficacious amendment for the remediation of compound heavy metal contamination in soil. However, the molecular mechanism of biochar-mediated tolerance to compound heavy metal toxicity in cotton is unknown. The objective of this research was to investigate the positive impact of biochar (10 g·kg−1) on reducing damage caused by compound heavy metals (Cd, Pb, and As) in cotton (Gossypium hirsutum L.). The results revealed that biochar reduced Cd concentrations by 24.9 % (roots), and decreased Pb concentrations by 37.1 % (roots) and 59.53 % (stems). Biochar maintained ionic homoeostasis by regulating the expression of metal transporter proteins such as ABC, HIPP, NRAMP3, PCR, and ZIP, and genes related to the carbon skeleton and plasma membrane. Biochar also downregulated genes related to photosynthesis, thereby increasing photosynthesis. Biochar re-established redox homoeostasis in cotton by activating signal transduction, which regulated the activity of the enzymes POD, SOD, and CAT activity; and the expression of related genes. This research revealed the molecular mechanism by which biochar confers resistance to the harmful effects of compound heavy metal toxicity in cotton. The application of biochar as a soil amendment to neutralise the toxicity of compound heavy metals is recommended for cash crop production.