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Redox transformation of mercury (Hg) is critical for Hg exchange at the air-water interface. However, the superoxide radicals (O 2 •─ ) contribution of microalgal-fungal symbiotic systems in lake water to Hg(II) reduction is mainly unknown. Here, we studied the enhanced potential for O 2 •─ production by the coupling effect between microalgae and fungi. The relationships between microenvironment, microorganisms, and O 2 •─ production were also investigated. Furthermore, the implication of O 2 •─ for Hg(II) reduction was explored. The results showed that the coupling effect of microalgae and fungi enhanced O 2 •─ generation in the symbiotic systems, and the O 2 •─ generation peaked on day 4 in the lake water at 160.51 ± 13.06-173.28 ± 18.21 μmol/kg FW (fresh weight). In addition, O 2 •- exhibited circadian fluctuations that correlated with changes in dissolved oxygen content and redox potential on the inter-spherical interface of microalgal-fungal consortia. Partial least squares path modeling (PLS-PM) indicates that O 2 •─ formation was primarily associated with microenvironmental factors and microbial metabolic processes. The experimental results suggest that O 2 •─ in the microalgal-fungal systems could mediate Hg(II) reduction, promoting Hg conversion and cycling. The findings highlight the importance of microalgae and fungal symbiotic systems in Hg transformation in aquatic environments., 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.)

Reactive oxygen species (ROS) play crucial roles in element cycling and pollutant dynamics, but their variations and mechanisms in the rhizosphere of submerged macrophytes are poorly investigated. This study investigated the light-dark cycle fluctuations and periodic variations in ROS, redox-active substances, and microbial communities in the rhizosphere of Vallisneria natans. The results showed sustained production and significant diurnal fluctuations in the O 2 •- and •OH from 27.6 ± 3.7 to 61.7 ± 3.0 μmol/kg FW and 131.0 ± 6.8 to 195.4 ± 8.7 μmol/kg FW, respectively, which simultaneously fluctuated with the redox-active substances. The ROS contents in the rhizosphere were higher than those observed in non-rhizosphere sediments over the V. natans growth period, exhibiting increasing-decreasing trends. According to the redundancy analysis results, water-soluble phenols, fungi, and bacteria were the main factors influencing ROS production in the rhizosphere, showing contribution rates of 74.0, 17.3, and 4.4 %, respectively. The results of partial least squares path modeling highlighted the coupled effects of redox-active substances and microbial metabolism. Our findings also demonstrated the degradation effect of ROS in rhizosphere sediments of submerged macrophytes. This study provides experimental evidence of ROS-related rhizosphere effects and further insights into submerged macrophytes-based ecological restoration., 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.)

The segmentation of the orbit in computed tomography (CT) images plays a crucial role in facilitating the quantitative analysis of orbital decompression surgery for patients with Thyroid-associated Ophthalmopathy (TAO). However, the task of orbit segmentation, particularly in postoperative images, remains challenging due to the significant shape variation and limited amount of labeled data. In this paper, we present a two-stage semi-supervised framework for the automatic segmentation of the orbit in both preoperative and postoperative images, which consists of a pseudo-label generation stage and a semi-supervised segmentation stage. A Paired Copy-Paste strategy is concurrently introduced to proficiently amalgamate features extracted from both preoperative and postoperative images, thereby augmenting the network discriminative capability in discerning changes within orbital boundaries. More specifically, we employ a random cropping technique to transfer regions from labeled preoperative images (foreground) onto unlabeled postoperative images (background), as well as unlabeled preoperative images (foreground) onto labeled postoperative images (background). It is imperative to acknowledge that every set of preoperative and postoperative images belongs to the identical patient. The semi-supervised segmentation network (stage 2) utilizes a combination of mixed supervisory signals from pseudo labels (stage 1) and ground truth to process the two mixed images. The training and testing of the proposed method have been conducted on the CT dataset obtained from the Eye Hospital of Wenzhou Medical University. The experimental results demonstrate that the proposed method achieves a mean Dice similarity coefficient (DSC) of 91.92% with only 5% labeled data, surpassing the performance of the current state-of-the-art method by 2.4%., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Feature matching of monocular laparoscopic videos is crucial for visualization enhancement in computer-assisted surgery, and the keys to conducting high-quality matches are accurate homography estimation, relative pose estimation, as well as sufficient matches and fast calculation. However, limited by various monocular laparoscopic imaging characteristics such as highlight noises, motion blur, texture interference and illumination variation, most exiting feature matching methods face the challenges of producing high-quality matches efficiently and sufficiently. To overcome these limitations, this paper presents a novel sequential coupling feature descriptor to extract and express multilevel feature maps efficiently, and a dual-correlate optimized coarse-fine strategy to establish dense matches in coarse level and adjust pixel-wise matches in fine level. Firstly, a novel sequential coupling swin transformer layer is designed in feature descriptor to learn and extract multilevel feature representations richly without increasing complexity. Then, a dual-correlate optimized coarse-fine strategy is proposed to match coarse feature sequences under low resolution, and the correlated fine feature sequences is optimized to refine pixel-wise matches based on coarse matching priors. Finally, the sequential coupling feature descriptor and dual-correlate optimization are merged into the Sequential Coupling Dual-Correlate Network (SeCo DC-Net) to produce high-quality matches. The evaluation is conducted on two public laparoscopic datasets: Scared and EndoSLAM, and the experimental results show the proposed network outperforms state-of-the-art methods in homography estimation, relative pose estimation, reprojection error, matching pairs number and inference runtime. The source code is publicly available at https://github.com/Iheckzza/FeatureMatching., 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 © 2023. Published by Elsevier Ltd.)

Automatic vessel segmentation is a critical area of research in medical image analysis, as it can greatly assist doctors in accurately and efficiently diagnosing vascular diseases. However, accurately extracting the complete vessel structure from images remains a challenge due to issues such as uneven contrast and background noise. Existing methods primarily focus on segmenting individual pixels and often fail to consider vessel features and morphology. As a result, these methods often produce fragmented results and misidentify vessel-like background noise, leading to missing and outlier points in the overall segmentation. To address these issues, this paper proposes a novel approach called the progressive edge information aggregation network for vessel segmentation (PEA-Net). The proposed method consists of several key components. First, a dual-stream receptive field encoder (DRE) is introduced to preserve fine structural features and mitigate false positive predictions caused by background noise. This is achieved by combining vessel morphological features obtained from different receptive field sizes. Second, a progressive complementary fusion (PCF) module is designed to enhance fine vessel detection and improve connectivity. This module complements the decoding path by combining features from previous iterations and the DRE, incorporating nonsalient information. Additionally, segmentation-edge decoupling enhancement (SDE) modules are employed as decoders to integrate upsampling features with nonsalient information provided by the PCF. This integration enhances both edge and segmentation information. The features in the skip connection and decoding path are iteratively updated to progressively aggregate fine structure information, thereby optimizing segmentation results and reducing topological disconnections. Experimental results on multiple datasets demonstrate that the proposed PEA-Net model and strategy achieve optimal performance in both pixel-level and topology-level metrics., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Monocular depth estimation plays a fundamental role in clinical endoscopy surgery. However, the coherent illumination, smooth surfaces, and texture-less nature of endoscopy images present significant challenges to traditional depth estimation methods. Existing approaches struggle to accurately perceive depth in such settings., Method: To overcome these challenges, this paper proposes a novel multi-scale residual fusion method for estimating the depth of monocular endoscopy images. Specifically, we address the issue of coherent illumination by leveraging image frequency domain component space transformation, thereby enhancing the stability of the scene's light source. Moreover, we employ an image radiation intensity attenuation model to estimate the initial depth map. Finally, to refine the accuracy of depth estimation, we utilize a multi-scale residual fusion optimization technique., Results: To evaluate the performance of our proposed method, extensive experiments were conducted on public datasets. The structural similarity measures for continuous frames in three distinct clinical data scenes reached impressive values of 0.94, 0.82, and 0.84, respectively. These results demonstrate the effectiveness of our approach in capturing the intricate details of endoscopy images. Furthermore, the depth estimation accuracy achieved remarkable levels of 89.3 % and 91.2 % for the two models' data, respectively, underscoring the robustness of our method., Conclusions: Overall, the promising results obtained on public datasets highlight the significant potential of our method for clinical applications, facilitating reliable depth estimation and enhancing the quality of endoscopy surgical procedures., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest related to this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fractional flow reserve (FFR) is considered as the gold standard for diagnosing coronary myocardial ischemia. Existing 3D computational fluid dynamics (CFD) methods attempt to predict FFR noninvasively using coronary computed tomography angiography (CTA). However, the accuracy and efficiency of the 3D CFD methods in coronary arteries are considerably limited. In this work, we introduce a multi-dimensional CFD framework that improves the accuracy of FFR prediction by estimating 0D patient-specific boundary conditions, and increases the efficiency by generating 3D initial conditions. The multi-dimensional CFD models contain the 3D vascular model for coronary simulation, the 1D vascular model for iterative optimization, and the 0D vascular model for boundary conditions expression. To improve the accuracy, we utilize clinical parameters to derive 0D patient-specific boundary conditions with an optimization algorithm. To improve the efficiency, we evaluate the convergence state using the 1D vascular model and obtain the convergence parameters to generate appropriate 3D initial conditions. The 0D patient-specific boundary conditions and the 3D initial conditions are used to predict FFR (FFR C ). We conducted a retrospective study involving 40 patients (61 diseased vessels) with invasive FFR and their corresponding CTA images. The results demonstrate that the FFR C and the invasive FFR have a strong linear correlation (r = 0.80, p < 0.001) and high consistency (mean difference: 0.014 ±0.071). After applying the cut-off value of FFR (0.8), the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR C were 88.5%, 93.3%, 83.9%, 84.8%, and 92.9%, respectively. Compared with the conventional zero initial conditions method, our method improves prediction efficiency by 71.3% per case. Therefore, our multi-dimensional CFD framework is capable of improving the accuracy and efficiency of FFR prediction significantly., 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 © 2023 Elsevier Ltd. All rights reserved.)

Peripheral blood mononuclear cells (PBMCs) were derived from a 67-year-old Chinese male. We used non-integrating episomal vectors containing OCT4, SOX2, KLF4 and c-MYC to reprogram PBMCs into induced pluripotent stem cell (iPSCs). This iPSC line, SDPHi003-A, have a normal karyotype, expressed pluripotent markers and have the potential for trilineage differentiation. This iPSC line can be used as a control for disease modeling studies and contribute to the research exploring disease pathogenesis., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Here, an induced pluripotent stem cell (iPSC) line from a patient with lung neuroendocrine carcinoma was generated. The iPSCs were developed using nonintegrating episomal vectors carrying OCT4, SOX2, KLF4, BCL-XL and c-MYC. The established iPSCs (SDPHi002-A) had normal karyotype, excellent differentiation potential in vitro, showing pluripotent stem cell morphology and high expression of pluripotent markers., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Studies have found that different immune subtypes are present in the same tumor. Different tumor subtypes have different tumor microenvironments (TME). This means that the efficacy of immunotherapy in actual applications will, therefore, have different results. Existing tumor immune subtype studies have mostly focused on immune cells, stromal cells, genes and molecules without considering the presence of microbes. Some studies have shown that microflora can strongly promote many gastrointestinal cancers. The microbiome has, therefore, become an important biomarker and regulatory factor of cancer progression and therapeutic responses. In addition, the presence of microflora can strongly regulate the host immune system, indirectly affecting tumor growth. Taken together, it is important to study the relationships that develop among tumor tissue microorganisms, tumor immune subtype, and the TME. In this study, correlations between microbial abundance, immune cell infiltration, immune gene expression and tumor immune subtype were studied. To accomplish this, tissue microorganisms and immune cell ratios with significant differences between the different cancers were obtained by comparing 203 gastric cancer and intestinal cancer samples. Two immune subtypes of intestinal samples were obtained by K-means clustering algorithm and tissue microorganisms, immune cell ratios and immune-related genes with significant differences between different immune subtypes were screened through Wilcoxon rank sum test. The results showed that Clostridioides difficile, Aspergillus fumigatus, Yarrowia lipolytica, and Fusarium pseudograminearum were all closely associated with the identified tumor immune subtypes. Our open-source software is freely available from GitHub at https://github.com/gutmicrobes/IMM-subtype.git., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: This study aimed to evaluate the potential budget impact of nusinersen in the treatment of spinal muscular atrophy (SMA) from the perspective of the basic medical insurance payer in China., Methods: A budget impact analysis model was developed according to ISPOR budget impact analysis guidelines; we integrated health resource consumption, epidemiology, and market data for the treatment of patients with SMA in China, to estimate the impact of nusinersen on basic medical insurance. The microcosting method was conducted to evaluate the treatment cost. One-way sensitivity analysis was performed to explore the stability of the results., Results: If nusinersen could be reimbursed, the impact on the medical insurance funds in the next 1 to 3 years will be 253 million, 333 million, and 426 million, respectively. In addition, it can reduce 0.73 million, 2.17 million, and 2.22 million in complication costs, respectively., Conclusions: SMA is a rare disease with a very low prevalence; reimbursement of nusinersen will lead to a limited impact on the basic medical insurance and improve the accessibility of treatment., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

The demand to control eutrophication in water bodies and the risk of phosphorus scarcity have prompted the search for treatment technologies for phosphorus recovery. In this study, ball-milled Ca-loaded biochar (BMCa@BC) composites were prepared with CaO and corn stover biochar as raw materials by a new ball-milling method to recover phosphorus from water bodies. Experimental results demonstrated that BMCa@BC could efficiently adsorb phosphorus in water bodies with an excellent sorption capacity of 329 mg P/g. Hydrogen bonding, electrostatic attraction, complexation, and surface precipitation were involved in adsorption process. In addition, phosphorus recovered by BMCa@BC had high bioavailability (86.7 % of TP) and low loss (3.3 % of TP) and was a potential slow-release fertilizer. P-laden BMCa@BC significantly enhanced seed germination and growth in planting experiments, proving that it could be used as a substitute for P-based fertilizer. After five cycles of regeneration, BMCa@BC still showed good adsorption recovery and the P-enriched desorption solution could be recovered as Ca-P products with the fertilizer value. Overall, BMCa@BC has good cost-effectiveness and practical applicability in phosphorus recovery. This provides a new way to recover and reuse phosphorus effectively., 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.)

Accurate detection of coronary artery stenosis in X-ray angiography (XRA) images is crucial for the diagnosis and treatment of coronary artery disease. However, stenosis detection remains a challenging task due to complicated vascular structures, poor imaging quality, and fickle lesions. While devoted to accurate stenosis detection, most methods are inefficient in the exploitation of spatio-temporal information of XRA sequences, leading to a limited performance on the task. To overcome the problem, we propose a new stenosis detection framework based on a Transformer-based module to aggregate proposal-level spatio-temporal features. In the module, proposal-shifted spatio-temporal tokenization (PSSTT) scheme is devised to gather spatio-temporal region-of-interest (RoI) features for obtaining visual tokens within a local window. Then, the Transformer-based feature aggregation (TFA) network takes the tokens as the inputs to enhance the RoI features by learning the long-range spatio-temporal context for final stenosis prediction. The effectiveness of our method was validated by conducting qualitative and quantitative experiments on 233 XRA sequences of coronary artery. Our method achieves a high F 1 score of 90.88%, outperforming other 15 state-of-the-art detection methods. It demonstrates that our method can perform accurate stenosis detection from XRA images due to the strong ability to aggregate spatio-temporal features., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: No studies evaluated the role of F8 mutations in outcomes for low-dose immune tolerance induction (ITI) in people with severe hemophilia A (SHA) with high-titer inhibitors., Objectives: To explore the association between F8 mutation types and low-dose ITI outcomes in children with SHA with high-titer inhibitors., Methods: Children SHA with high-titer inhibitors who received low-dose ITI therapy at least for 1 year were included in this study. Based on the risk of inhibitor development, F8 mutations were classified into a high-risk group and a non-high-risk group. Rapid tolerance and the final ITI outcomes were assessed at the 12th and 24th month of treatment, respectively, and the predictor of outcomes was analyzed., Results: Of 104 children included, 101 had F8 mutations identified. The children with non-high-risk mutations presented a higher rate of rapid tolerance than those with high-risk mutations (61.0% vs. 29.2%; p  = 0.006). Among 72 children beyond 24 months of ITI, 55 children (76.4%) achieved success, 3 (4.2%) achieved partial success, and 14 (19.4%) failed. The children in the non-high-risk group showed a higher success rate (86.8% vs. 43.8%; p  = 0.001) and a shorter time to success (mean time, 9.3 months vs. 13.2 months; p  = 0.04) compared to those in the high-risk group. In multivariable logistic regression, F8 mutations were an independent predictor of ITI success (non-high-risk group vs. high-risk group, adjusted odds ratio [OR], 20.3; 95% confidence interval [CI], 3.5-117.8), as was the interval from inhibitor diagnosis to ITI start (adjusted OR, 0.95; 95% CI, 0.90-0.99). They remained the significant predictors when success time was taken into account in a Cox model., Conclusions: Types of F8 mutation were a key predictor of outcomes for low-dose ITI in children with SHA with high-titer inhibitors. It can help to stratify the prognosis and guide clinical decisions., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Marker-based augmented reality (AR) calibration methods for surgical navigation often require a second computed tomography scan of the patient, and their clinical application is limited due to high manufacturing costs and low accuracy., Methods: This work introduces a novel type of AR calibration framework that combines a Microsoft HoloLens device with a single camera registration module for surgical navigation. A camera is used to gather multi-view images of a patient for reconstruction in this framework. A shape feature matching-based search method is proposed to adjust the size of the reconstructed model. The double clustering-based 3D point cloud segmentation method and 3D line segment detection method are also proposed to extract the corner points of the image marker. The corner points are the registration data of the image marker. A feature triangulation iteration-based registration method is proposed to quickly and accurately calibrate the pose relationship between the image marker and the patient in the virtual and real space. The patient model after registration is wirelessly transmitted to the HoloLens device to display the AR scene., Results: The proposed approach was used to conduct accuracy verification experiments on the phantoms and volunteers, which were compared with six advanced AR calibration methods. The proposed method obtained average fusion errors of 0.70 ± 0.16 and 0.91 ± 0.13 mm in phantom and volunteer experiments, respectively. The fusion accuracy of the proposed method is the highest among all comparison methods. A volunteer liver puncture clinical simulation experiment was also conducted to show the clinical feasibility., Conclusions: Our experiments proved the effectiveness of the proposed AR calibration method, and revealed a considerable potential for improving surgical performance., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alcoholic liver disease (ALD) has caused a serious burden on public and personal health in crowd with ethanol abuse. The effects of insulin resistance (IR) on ALD and the mechanisms underlying these responses are still not well understood. In this study, we investigated the changes of liver injury, inflammation, apoptosis, mitochondrial dysfunction and CYP2E1 changes in liver of mice exposed to ethanol with IR or not. We found IR increased the sensitivity of liver injury in mice exposed to ethanol, manifested as the increase serum activities of AST and ALT, the accumulation of triglycerides, the deterioration of liver pathology and increase of inflammatory factors. IR also exacerbated apoptosis and mitochondrial dysfunction in liver of mice exposed to ethanol. The increase of oxidative stress and the decrease of antioxidant defense ability might be responsible for the sensitizing effects of IR on ethanol-induced liver injury, supported by the increase of MDA levels and the decline of GSH/GSSG, the inactivation of antioxidant enzymes SOD, GR through the inhibition of Nrf-2 pathway. The activation of CYP2E1 might be also involved in the sensitizing effects of IR on ethanol induced liver injury in mice. These results demonstrated that IR exhibited a significant pro-oxidative and pro-apoptosis effects to aggravate alcoholic liver injury. Our study helped us to better understand the sensitive role of IR on ALD and suggested that alcohol intake may be more harmful for people with IR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Type of F8  gene mutation is the most important risk factor for inhibitor development in people with severe hemophilia A. However, there are few large cohort studies on the F8  mutation spectrum of people with severe hemophilia A with inhibitors., Objective: This was the first large cohort study in children with severe hemophilia A with inhibitors from China that aimed to analyze the association between F8 variant types and inhibitor status., Methods: The single-center retrospective cohort study was conducted on children with severe hemophilia A with inhibitors admitted from January 2015 to December 2021. The clinical data were collected, and F8  genetic tests were performed., Results: Among the 203 patients investigated, a mutation in F8 was identified in 196 cases. Most patients had deleterious mutations (153; 75.4%), including 82 cases of intron 22 inversions (40.4%); 40 cases of nonsense mutations (19.7%), with 15 cases in the light chain and 25 cases in the heavy chain; and 31 cases of large deletions or insertions (15.3%), with 29 cases involving more than one exon and 2 cases involving one exon. The large deletions or insertions encompassing multiple exons and nonsense mutations residing in the light chain were associated with not only the progression to a high-titer inhibitor ( P  < .05) but also higher peak inhibitor titer ( P  < .05)., Conclusion: The F8  gene deleterious mutations, including intron 22 inversions, nonsense mutations, and large deletions or insertions, constitute the main mutation types in people with severe hemophilia A with inhibitors in China, with the latter mutation types (large deletions or insertions in multiple exons, and nonsense mutations in the light chain) signifying for a higher peak titer of inhibitor., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Introduction: A physiological hypoxia environment exists at maternal-fetal interface during early pregnancy. In addition, there is a pathological hypoxic microenvironment in patients with preeclampsia. Therefore, investigating the hypoxic adaptation and the effects of hypoxia on trophoblasts transcriptome is helpful to better understand the function and regulatory mechanism of trophoblasts at the maternal-fetal interface., Methods: Trophoblast cell line HTR-8/SVneo was cultured under normoxia and hypoxia for 24 h, the full transcriptome was analyzed via RNA-Seq. GO and KEGG enrichment were performed on differentially expressed mRNA, adjacent genes of differentially expressed lncRNA, host genes of differentially expressed circRNA and target genes of differential expressed miRNA., Results: The results showed that hypoxia differentially regulated 373 mRNAs, 334 lncRNAs, 71 circRNAs and 33 miRNAs. GO and KEGG enrichment showed that hypoxia negatively regulated TLR3 and PI3K-Akt signaling pathways. Consistently, we found hypoxia significantly inhibited TLR3 agonist-induced cytokines expression and the phosphorylation of Akt and mTOR., Discussion: Our study obtained the full transcriptome data and potential regulatory network of trophoblasts under hypoxia, providing supportive data for revealing the function of trophoblasts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The need for an effective tool to predict prognosis of head and neck squamous cell carcinoma (HNSCC) patients is critical and unmet. Microbiota has recently been found involved in tumor progression and response to immunotherapy. However, the association of microbiota with the prognosis of HNSCC patients remains obscure. This study aims to investigate the association between tumor microbiota and outcomes of HNSCC patients., Methods: A retrospective study including 129 primary tumors of HNSCC was conducted. Using 16S rRNA sequencing, the profile and the composition of tumor microbiota were measured and their associations with overall survival (OS) and disease free survival (DFS) were examined., Results: We observed a reduced richness and enriched abundances of genera Schlegelella and Methyloversatilis in tumor microbiota of HNSCC patients with poor prognosis. However, a richer tumor microbiota with greater abundances of genera Bacillus, and Lactobacillus and Sphingomonas was characterized in the patients with favorable prognosis.The ratio of these differentially abundant taxa, microbial dysbiosis index (MDI), was significantly associated with OS (hazard ratio [HR], 4.67, 95% confidence interval [CI], 2.51 to 8.69,P < 0.001) and DFS (HR, 2.89; 95% CI, 1.74 to 4.80, P < 0.001) independently of age, tumor size, lymph node metastasis, differentiation and p16 status. The risk score of multivariate Cox regression exhibited an excellent performance for estimating three-year OS (AUC of 0.826). We also found a richer tumor microbiota was correlated with moderate peritumoral inflammatory infiltration., Conclusion: These results indicate that tumor microbiota associates with outcomes of HNSCC patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Augmented reality (AR) based fusion imaging in endoscopic surgeries rely on the quality of image-to-patient registration and camera calibration, and these two offline steps are usually performed independently to get the target transformation separately. The optimal solution can be obtained under independent conditions but may not be globally optimal. All residual errors will be accumulated and eventually lead to inaccurate AR fusion., Methods: After a careful analysis of the principle of AR imaging, a robust online calibration framework was proposed for an endoscopic camera to enable accurate AR fusion. A 2D checkerboard-based homography estimation algorithm was proposed to estimate the local pose of the endoscopic camera, and the least square method was used to calculate the compensation matrix in combination with the optical tracking system., Results: In comparison with conventional methods, the proposed compensation method improved the performance of AR fusion, which reduced physical error by up to 82%, reduced pixel error by up to 83%, and improved target coverage by up to 6%. Experimental results of simulating mechanical noise revealed that the proposed compensation method effectively corrected the fusion errors caused by the rotation of the endoscopic tube without recalibrating the camera. Furthermore, the simulation results revealed the robustness of the proposed compensation method to noises., Conclusions: Overall, the experiment results proved the effectiveness of the proposed compensation method and online calibration framework, and revealed a considerable potential in clinical practice., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this study, with the green tea extraction solution as a reducing agent and green tea residues as a raw material of biochar, green nano zero-valent iron biochar (G-nZVI-BC) was prepared with the green synthesis method and then combined with potassium persulfate to degrade p-nitrophenol in water. Compared with zero-valent iron-loaded biochar (C-nZVI-BC) prepared by the traditional chemical liquid phase synthesis method, G-nZVI-BC containing tea polyphenols further improved dispersibility of Fe 0 on biochar, prevented nZVI agglomeration on BC, and promoted PNP degradation. The system constructed by G-nZVI-BC/PDS showed the high oxidation resistance than the C-nZVI-BC/PDS system, thus endowing the synthesis material with long-term reactivity. Both the radical pathway and non-radical pathways contributed to catalytic degradation and free radicals played a key role. The G-nZVI-BC/PDS system realized the good removal effect on PNP in the pH range of 3.06-9.23. The reusability of G-nZVI-BC and the PNP removal effect in water body conditions indicated that G-nZVI-BC had a good application prospect in the field of water treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Disturbed flow leads to increased inflammatory responses of endothelial cells (ECs) prone to atherogenic state. Currently, little is known about the physiological mechanisms protecting vasculature against disturbed flow-activated ECs leading to atherosclerosis. Understanding the protective mediators involved in EC activation could provide novel therapeutic strategies for atherosclerosis. The extracellular matrix microenvironment profoundly regulates cellular homeostasis. A non-EC resident ECM protein, cartilage oligomeric matrix protein (COMP), has diverse protective roles in the cardiovascular system. To determine whether COMP could protect against disturbed flow-activated EC and atherosclerosis, we compared oscillatory shear stress (OSS) induced EC activation coated with various ECM proteins. Purified COMP inhibited EC activation caused by OSS. EC activation was upregulated in the aortic arch where the flow is disturbed in COMP -/- mice as compared with wild-type mice under physiological conditions or pathologically in partially ligated mouse carotid arteries. Mechanistically, co-immunoprecipitation, mammalian two-hybrid and FRET assay results suggest that COMP bound directly to integrin α5 via its C-terminus. We next synthesized a COMP-derived peptidomimetics (CCPep24) mimicking a specific COMP-integrin α5 interaction and found that CCPep24 protected against EC activation and atherogenesis in vivo. This study extends our current understanding of how ECM and flow coordinately fine-tune EC homeostasis and reveals the potential therapeutic effect of COMP or COMP-derived peptidomimetics on blocking aberrant integrin α5 activation, inflammatory EC activation and atherosclerosis pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Graph-based groupwise registration methods are widely used in atlas construction. Given a group of images, a graph is built whose nodes represent the images, and whose edges represent a geodesic path between two nodes. The distribution of images on an image manifold is explored through edge traversal in a graph. The final atlas is a mean image at the population center of the distribution on the manifold. The procedure of warping all images to the mean image turns to dynamic graph shrinkage in which nodes become closer to each other. Most conventional groupwise registration frameworks construct and shrink a graph without considering the local distribution of images on the dataset manifold and the local structure variations between image pairs. Neglecting the local information fundamentally decrease the accuracy and efficiency when population atlases are built for organs with large inter-subject anatomical variabilities. To overcome the problem, this paper proposes a global-local graph shrinkage approach that can generate accurate atlas. A connected graph is constructed automatically based on global similarities across the images to explore the global distribution. A local image distribution obtained by image clustering is used to simplify the edges of the constructed graph. Subsequently, local image similarities refine the deformation estimated through global image similarity for each image warping along the graph edges. Through the image warping, the overall simplified graph shrinks gradually to yield the atlas with respecting both global and local features. The proposed method is evaluated on 61 synthetic and 20 clinical liver datasets, and the results are compared with those of six state-of-the-art groupwise registration methods. The experimental results show that the proposed method outperforms non-global-local method approaches in terms of accuracy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The major histocompatibility complex class I chain-related molecule A (MICA) is one of the natural killer group 2D ligands. Soluble major histocompatibility complex class I chain-related molecule A (sMICA) mediates tumor immune escape, but the mechanism is not fully understood. In this study, we examined the expression of phospho-p38, matrix metalloproteinase 9 (MMP-9), and MICA and their relationships among each other in pituitary adenoma tissues to provide a histologic basis for the mechanism of pituitary adenoma immune escape., Methods: We applied immunohistochemistry, real-time quantitative reverse-transcriptase polymerase chain reaction, and Western blot to detect phospho-p38, MMP-9, and MICA expression at the mRNA and protein levels in pituitary adenoma tissues. Enzyme-linked immunosorbent assay was used to examine the expression levels of MMP-9 and sMICA in peripheral blood serum from patients with pituitary adenoma., Results: We found that p38, MICA, and MMP-9 mRNA levels were greater in pituitary adenomas than in normal tissues. The phospho-p38, MMP-9, and MICA proteins were overexpressed in pituitary adenomas, and the expression of MMP-9 and MICA were positively correlated with the expression of phospho-p38. In addition, the serum levels of sMICA and MMP-9 proteins in pituitary adenoma patients were significantly greater than those in normal controls., Conclusions: These findings suggest that activation of the p38/mitogen-activated protein kinase pathway may increase MICA expression and induce MMP-9 expression. MMP-9 is involved in the shedding of sMICA from MICA to promote tumor immune escape. Furthermore, p38/mitogen-activated protein kinase could potentially represent a novel target for inhibiting pituitary adenoma immune escape., (Copyright © 2018. Published by Elsevier Inc.)

Diabetic retinopathy (DR) is the most frequent microvascular complications of diabetes and the leading cause of blindness in adults worldwide. Non-proliferative DR (NPDR) is the first stage of DR but currently has few recommended intervention. Eicosanoids play important roles in maintaining vessel homeostasis. However, the functions of eicosanoids in NPDR are still unknown. In this study, we investigated the eicosanoids profile difference in plasma between type 2 diabetes with NPDR or not. A total of 50 patients with type 2 diabetes were recruited and divided into non-DR (NDR) group and NPDR group based on fundus photographs. The eicosanoids profiles in plasma were determined by LC-MS/MS. Adhesion and transwell assay were used to detect the adhesion and migration effects of metabolites on primary bovine retinal pericyte cells (BRPC), respectively. Streptomycin (STZ)-induced diabetic mouse model was used to test the protective effects of selected metabolites according to retinal immunofluorescence staining and fluorescence confocal microscopy. Prostaglandin 2α (PGF2α) was decreased significantly in NPDR group compared to NDR group and negatively correlated with NPDR. In vitro, PGF2α was found to accelerate adhesion and migration by activating prostaglandin F receptor (FP receptor) and subsequent increasing RhoA activity in primary bovine retinal pericyte. Administration of PGF2α analogue diminished the damage on retinal capillary in an STZ-induced diabetic mouse model. Our results suggested that PGF2α may be a protective factor in the progression of NPDR in T2D patients. The protective mechanism of PGF2α was to increase pericyte mobility through FP receptor/RhoA pathway., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This paper quantifies the registration and fusion display errors of augmented reality-based nasal endoscopic surgery (ARNES). We comparatively investigated the spatial calibration process for front-end endoscopy and redefined the accuracy level of a calibrated endoscope by using a calibration tool with improved structural reliability. We also studied how registration accuracy was combined with the number and distribution of the deployed fiducial points (FPs) for positioning and the measured registration time. A physically integrated ARNES prototype was customarily configured for performance evaluation in skull base tumor resection surgery with an innovative approach of dynamic endoscopic vision expansion. As advised by surgical experts in otolaryngology, we proposed a hierarchical rendering scheme to properly adapt the fused images with the required visual sensation. By constraining the rendered sight in a known depth and radius, the visual focus of the surgeon can be induced only on the anticipated critical anatomies and vessel structures to avoid misguidance. Furthermore, error analysis was conducted to examine the feasibility of hybrid optical tracking based on point cloud, which was proposed in our previous work as an in-surgery registration solution. Measured results indicated that the error of target registration for ARNES can be reduced to 0.77 ± 0.07 mm. For initial registration, our results suggest that a trade-off for a new minimal time of registration can be reached when the distribution of five FPs is considered. For in-surgery registration, our findings reveal that the intrinsic registration error is a major cause of performance loss. Rigid model and cadaver experiments confirmed that the scenic integration and display fluency of ARNES are smooth, as demonstrated by three clinical trials that surpassed practicality., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr(-/-) mouse aortas, EC-ABCG1-Tg/Ldlr(-/-) aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr(-/-) mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Chromosome 3q26.2 abnormalities in acute myeloid leukemia, including inv(3)/t(3;3) and t(3;21), have been studied and are associated with a poor prognosis. Their prevalence, response to tyrosine kinase inhibitor (TKI) treatment, and prognostic significance in chronic myelogenous leukemia (CML) are largely unknown. In this study, we explored these aspects using a cohort of 2013 patients with CML diagnosed in the era of TKI therapy. Chromosome 3 abnormalities were observed in 116 (5.8%) of 2013 cases. These cases were divided into 5 distinct groups: A, inv(3)(q21q26.2)/t(3;3)(q21;q26.2), 26%; B, t(3;21)(q26.2;q22), 17%; C, other 3q26.2 rearrangements, 7%; D, rearrangements involving chromosome 3 other than 3q26.2 locus, 32%; and E, gain or loss of partial or whole chromosome 3, 18%. In all, 3q26.2 rearrangements were the most common chromosome 3 abnormalities (50%, groups A-C). 3q26.2 rearrangements emerged at different leukemic phases. For cases with 3q26.2 rearrangements that initially emerged in chronic or accelerated phase, they had a high rate of transformation to blast phase. Patients with 3q26.2 abnormalities showed a marginal response to TKI treatment, and no patients achieved a long-term sustainable response at a cytogenetic or molecular level. Compared with other chromosomal abnormalities in CML, patients with 3q26.2 rearrangements had poorer overall survival. The presence or absence of other concurrent chromosomal abnormalities did not affect survival in these patients, reflecting the predominant role of 3q26.2 rearrangements in determining prognosis. Interestingly, although heterogeneous, chromosome 3 abnormalities involving non-3q26.2 loci (groups D, E) also conferred a worse prognosis compared with changes involving other chromosomes in this cohort., (© 2015 by The American Society of Hematology.)

The schistosomal tegument is a dynamic host-interactive layer. Proteins exposed to the host on the tegumental surface are important for completion of the parasitic lifecycle. Dysferlin is a member of the ferlin family and is involved in plasma membrane repair. Based on the results of a proteomics study of tegument surface proteins of Schistosoma japonicum in our laboratory, dysferlin was identified as a tegumental protein of S. japonicum. The gene encoding S. japonicum dysferlin (SjDF), which codes for several Ca(2+) binding sites, was cloned, expressed in Escherichia coli, and characterized. Western blot analysis revealed that recombinant SjDF had good immunogenicity. Real-time RT-PCR analysis showed that SjDF was upregulated mainly in adult worms and the transcription level in 42-day-old female worms was significantly higher than that in males. Immunofluorescence analysis revealed that SjDF was mainly distributed in the tegument at various developmental stages. Experimental mice were treated with praziquantel and at 35days post-infection, we noted that damage to the tegument and subtegument worsened and did not recover at 36h post-treatment in the high-dose group and was accompanied by downregulation of SjDF mRNA, while the damage was less severe and recovered by this time in the low-dose group, and accompanied by upregulation of SjDF. Our results suggested that SjDF is a tegumental protein that may be important in schistosomal development and may participate in the repair process in muscle and tegument, and could present a viable vaccine candidate for schistosomiasis., (© 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

The human X chromosome contains a large number of inverted repeat DNA palindromes. Although arbitrary substitutions destroyed the inverted repeat structure of MAGEA/CSAG-palindrome during the evolutionary process of the primates, most of the substitutions are compensatory. Using maximum parsimony, it is demonstrated that the compensatory substitutions are prone to occur between bases with similar structures on the human, chimpanzee and orangutan MAGEA/CSAG-palindromes. Furthermore, it is found that MAGEA/CSAG genes also exist in orangutan and rhesus monkey palindromes by homologous searching. This suggests that the MAGEA/CSAG-palindrome might predate the divergence of human and other primate lineages. Comparative sequence analysis of the arms and genes on the primate MAGEA/CSAG-palindromes provides possible evidence of subsequently arm to arm gene conversion. These compensatory substitutions on the MAGEA/CSAG-palindrome of the primate X chromosomes play an important role in maintaining their structural symmetry during the process of formation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This work reported a novel poly(lactic-co-glycolic acid) (PLGA) composite nanofibres, Chitosan-graft-PLGA (CS-graft-PLGA), produced by the electrospinning technique. CS was grafted onto the PLGA surface via the cross-linking agents reacting with the PLGA with reactive carboxyl groups on its surfaces introduced from the alkali treatment. The CS grafting ratios of the electrospun CS-graft-PLGA nanofibres were about 2.43%, 4.34%, 16.97% and 39.4% after cross-linked for 12 h, 16 h, 20 h and 24 h, respectively. The electrospun CS-graft-PLGA nanofibres were significantly uniform and highly smooth without the occurrence of bead defects, even at high CS grafting ratio. The electrospun CS-graft-PLGA nanofibres not only possessed the improved hydrophilicity and the protein absorption property, but also maintained the good mechanical property. In addition, the CS grafting can be conducive to accelerate degradation rate of PLGA., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Derived from arachidonic acid, epoxyeicosatrienoic acids function as antihypertensive and antihypertrophic mediators in the cardiovascular system. Epoxyeicosatrienoic acids are generated by soluble epoxide hydrolase, an enzyme hydrolyzing the epoxide moiety of juvenile hormones in insects, and are endothelium-derived hyperpolarizing factors that induce vessel dilation for cardioprotection. Pharmacological inhibition and genetic ablation of soluble epoxide hydrolase increases the level of epoxyeicosatrienoic acids. Recent findings suggest that the level of soluble epoxide hydrolase in the heart and endothelium is upregulated by angiotensin II in vitro in cultured cardiomyocytes and vascular endothelial cells and in vivo in rodent models. Treatment with soluble epoxide hydrolase-selective inhibitors in angiotensin II-infused hypertensive rats increases the level of epoxyeicosatrienoic acids, with attendant decrease in systolic blood pressure. Shear stress, the physiological stimulation of vessel dilation, downregulates soluble epoxide hydrolase and hence increases epoxyeicosatrienoic acid level in endothelial cells. Because of the close association of the angiotensin II/soluble epoxide hydrolase/epoxyeicosatrienoic acid system and blood pressure regulation, pharmacological inhibition of soluble epoxide hydrolase would be a useful approach to prevent and treat angiotensin II-induced cardiac hypertrophy and hypertension, as well as vascular impairments.

Current models of left-right asymmetry hold that an early asymmetric signal is generated at the node and transduced to lateral plate mesoderm in a linear signal transduction cascade through the function of the Nodal signaling molecule. The Pitx2 homeobox gene functions at the final stages of this cascade to direct asymmetric morphogenesis of selected organs including the heart. We previously showed that Pitx2 regulated an asymmetric pathway that was independent of cardiac looping suggesting a second asymmetric cardiac pathway. It has been proposed that in the cardiac outflow tract Pitx2 functions in both cardiac neural crest, as a target of canonical Wnt-signaling, and in the mesoderm-derived cardiac second lineage. We used fate mapping, conditional loss of function, and chimera analysis in mice to investigate the role of Pitx2 in outflow tract morphogenesis. Our findings reveal that Pitx2 is dispensable in the cardiac neural crest but functions in second lineage myocardium revealing that this cardiac progenitor field is patterned asymmetrically.