Enhanced electrocatalytic biomass oxidation at low voltage by Ni2+-O-Pd interfaces.

Challenges in direct catalytic oxidation of biomass-derived aldehyde and alcohol into acid with high activity and selectivity hinder the widespread biomass application. Herein, we demonstrate that a Pd/Ni(OH)2 catalyst with abundant Ni2+-O-Pd interfaces allows electrooxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid with a selectivity near 100 % and 2, 5-furandicarboxylic acid yield of 97.3% at 0.6 volts (versus a reversible hydrogen electrode) in 1 M KOH electrolyte under ambient conditions. The rate-determining step of the intermediate oxidation of 5-hydroxymethyl-2-furancarboxylic acid is promoted by the increased OH species and low C-H activation energy barrier at Ni2+-O-Pd interfaces. Further, the Ni2+-O-Pd interfaces prevent the agglomeration of Pd nanoparticles during the reaction, greatly improving the stability of the catalyst. In this work, Pd/Ni(OH)2 catalyst can achieve 100% 5-hydroxymethylfurfural conversion and >90% 2, 5-furandicarboxylic acid selectivity in a flow-cell and work stably over 200 h under a fixed cell voltage of 0.85 V.

Alterations in metabolome and lipidome in patients with in-stent restenosis.

CONTEXT: In-stent restenosis (ISR) can lead to blood flow obstruction, insufficient blood supply to the brain, and may even result in serious complications such as stroke. Endothelial cell hyperproliferation and thrombosis are the primary etiologies, frequently resulting in alterations in intravascular metabolism. However, the metabolic changes related to this process are still undermined. OBJECTIVE: We tried to characterize the serum metabolome of patients with ISR and those with non-restenosis (NR) using metabolomics and lipidomics, exploring the key metabolic pathways of this pathological phenomenon. RESULTS: We observed that the cysteine and methionine pathways, which are associated with cell growth and oxidative homeostasis, showed the greatest increase in the ISR group compared to the NR group. Within this pathway, the levels of N-formyl-l-methionine and L-methionine significantly increased in the ISR group, along with elevated levels of downstream metabolites such as 2-ketobutyric acid, pyruvate, and taurocholate. Additionally, an increase in phosphatidylcholine (PC) and phosphatidylserine (PS), as well as a decrease in triacylglycerol in the ISR group, indicated active lipid metabolism in these patients, which could be a significant factor contributing to the recurrence of blood clots after stent placement. Importantly, phenol sulfate and PS(38:4) were identified as potential biomarkers for distinguishing ISR, with an area under the curve of more than 0.85. CONCLUSIONS: Our study revealed significant metabolic alterations in patients with ISR, particularly in the cysteine and methionine pathways, with phenol sulfate and PS(38:4) showing promise for ISR identification.

Recent development and applications of differential electrochemical mass spectrometry in emerging energy conversion and storage solutions.

Electrochemical energy conversion and storage are playing an increasingly important role in shaping the sustainable future. Differential electrochemical mass spectrometry (DEMS) offers an operando and cost-effective tool to monitor the evolution of gaseous/volatile intermediates and products during these processes. It can deliver potential-, time-, mass- and space-resolved signals which facilitate the understanding of reaction kinetics. In this review, we show the latest developments and applications of DEMS in various energy-related electrochemical reactions from three distinct perspectives. (I) What is DEMS addresses the working principles and key components of DEMS, highlighting the new and distinct instrumental configurations for different applications. (II) How to use DEMS tackles practical matters including the electrochemical test protocols, quantification of both potential and mass signals, and error analysis. (III) Where to apply DEMS is the focus of this review, dealing with concrete examples and unique values of DEMS studies in both energy conversion applications (CO2 reduction, water electrolysis, carbon corrosion, N-related catalysis, electrosynthesis, fuel cells, photo-electrocatalysis and beyond) and energy storage applications (Li-ion batteries and beyond, metal-air batteries, supercapacitors and flow batteries). The recent development of DEMS-hyphenated techniques and the outlook of the DEMS technique are discussed at the end. As DEMS celebrates its 40th anniversary in 2024, we hope this review can offer electrochemistry researchers a comprehensive understanding of the latest developments of DEMS and will inspire them to tackle emerging scientific questions using DEMS.

Nontuberculous mycobacterial disease in children: A systematic review and meta-analysis.

Background: The prevalence of nontuberculous mycobacterial (NTM) disease in children is increasing worldwide. The clinical manifestations of pediatric NTM patients are significantly different from those of adult patients, but the knowledge of the disease is generally poor. Methods: English databases (PubMed, Web of Science, Embase, BIOSIS) and Chinese databases (CNKI, Wanfan, VIP) were searched on October 15th, 2022. All the articles of cross-sectional and cohort studies reporting the species composition and lesion site of the NTM disease in children using well-recognized NTM species identification methods were taken into account. Using a random effects model, we assessed the disease lesion sites and the prevalence of different NTM species in pediatric NTM disease. Sources of heterogeneity were analyzed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. Results: The prevalence rates of NTM disease in children ranged between 0.6 and 5.36/100,000 in different countries, and Europe reported the highest prevalence rate. The most common clinical lesion site was lymph node, accounting for 71.1 % (55.0 %-83.2 %), followed by lung (19.3 %, 9.8%-34.4 %）and then skin and soft tissue (16.6 %,13.5%-20.3 %). Mycobacterium avium complex (MAC) was the most isolated NTM pathogen in children, accounting for 54.9 % (39.4%-69.6 %). Inconsistent with adult patients, Mycobacterium avium accounted for a dominant proportion in MAC than Mycobacterium intracellulare. Conclusions: The lymph node was the most affected organ in pediatric NTM disease, while Mycobacterium avium was the most isolated pathogenic species in children.

Demonstration Study of Reflector-Based Volumetric Speed-of-Sound Imaging With Linear Ultrasound Arrays.

Conventional B-mode ultrasound imaging has difficulty in delineating homogeneous soft tissues with similar acoustic impedances, as the reflectivity depends on the acoustic impedance at the interface. As a quantitative imaging biomarker sensitive to alteration of biomechanical properties, speed-of-sound (SoS) holds promising potential for tissue and disease differentiation such as delineation of different breast tissue types with similar acoustic impedance. Compared to two-dimensional (2D) SoS images, three-dimensional (3D) volumetric SoS images achieved through a full-angle ultrasound scan can reveal more intricate morphological structures of tissues; however, they generally require a ring transducer. In this study, we introduce a 3D SoS reconstruction system that utilizes hand-held linear arrays instead. This system employs a passive reflector positioned opposite the linear arrays, serving as an echogenic reference for time-of-flight (ToF) measurements, and a high-definition camera to track the location corresponding to each group of transmit-receive data. To merge these two streams of ToF measurements and location tracking, a voxel-based reconstruction algorithm is implemented. Experimental results with gelatin phantom and ex vivo tissue have demonstrated the stability of our proposed method. Moreover, the results underscore the potential of this system as a complementary diagnostic modality, particularly in the context of diseases such as breast cancer.

An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting.

BACKGROUND: Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. METHODS: In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. RESULTS: During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. CONCLUSION: The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.

Nano­selenium functionalized chitosan gel beads for Hg(II) removal from apple juice.

The presence of potentially toxic elements and compounds poses threats to the quality and safety of fruit juices. Among these, Hg(II) is considered as one of the most poisonous heavy metals to human health. Traditional chitosan-based and selenide-based adsorbents face challenges such as poor adsorption capacity and inconvenient separation in juice applications. In this study, we prepared nano­selenium functionalized chitosan gel beads (nanoSe@CBs) and illustrated the synergistic promotions between chitosan and nanoSe in removing Hg(II) from apple juice. The preparation conditions, adsorption behaviors, and adsorption mechanism of nanoSe@CBs were systematically investigated. The results revealed that the adsorption process was primarily controlled by chemical adsorption. At the 0.1 % dosage, the adsorbent exhibited high uptake, and the maximum adsorption capacity from the Langmuir isotherm model could reach 376.5 mg/g at room temperature. The adsorbent maintained high adsorption efficiency (> 90 %) across a wide range of Hg(II) concentrations (0.01 to 10 mg/L) and was unaffected by organic acids present in apple juice. Additionally, nanoSe@CBs showed negligible effects on the quality of apple juice. Overall, nanoSe@CBs open up possibilities to be used as a safe, low-cost and highly-efficient adsorbent for the removal of Hg(II) from juices and other liquid foods.

Simultaneous determination of subspecies and geographic origins of 110 rice cultivars by microsatellite markers.

Rice varieties of different subspecies types (indica rice and japonica rice) across various geographical origins (Hunan, Jiangsu, and Northeast China) were monitored using microsatellite markers (simple sequence repeats, SSR). 110 representative rice cultivars were collected from the main crop areas. Multiple methods including clustering analysis (neighbor-joining (NJ) method, unweighted pair-group method with arithmetic mean (UPGMA) method), principal component analysis (PCA) and model-based grouping were applied. The study revealed that 25 pairs of SSR markers exhibited a broad range of polymorphism information content (PIC) values, ranging from 0.240 to 0.830. Furthermore, our study successfully achieved a higher overall mean correct rate of 99.09% in determining the geographical origin of rice. Simultaneously, it accurately classified indica rice and japonica rice. These findings are significant as they provide an SSR fingerprint of 110 high-quality rice cultivars, serving as a valuable scientific resource for the detection of rice adulteration and traceability of its origin.

Integrating hydrogen utilization in CO2 electrolysis with reduced energy loss.

Electrochemical carbon dioxide reduction reaction using sustainable energy is a promising approach of synthesizing chemicals and fuels, yet is highly energy intensive. The oxygen evolution reaction is particularly problematic, which is kinetically sluggish and causes anodic carbon loss. In this context, we couple CO2 electrolysis with hydrogen oxidation reaction in a single electrochemical cell. A Ni(OH)2/NiOOH mediator is used to fully suppress the anodic carbon loss and hydrogen oxidation catalyst poisoning by migrated reaction products. This cell is highly flexible in producing either gaseous (CO) or soluble (formate) products with high selectivity (up to 95.3%) and stability (>100 h) at voltages below 0.9 V (50 mA cm-2). Importantly, thanks to the "transferred" oxygen evolution reaction to a water electrolyzer with thermodynamically and kinetically favored reaction conditions, the total polarization loss and energy consumption of our H2-integrated CO2 reduction reaction, including those for hydrogen generation, are reduced up to 22% and 42%, respectively. This work demonstrates the opportunity of combining CO2 electrolysis with the hydrogen economy, paving the way to the possible integration of various emerging energy conversion and storage approaches for improved energy/cost effectiveness.

Comparison of the in vitro antibacterial activity of ofloxacin, levofloxacin, moxifloxacin, sitafloxacin, finafloxacin, and delafloxacin against Mycobacterium tuberculosis strains isolated in China.

Objective: The resistance of Mycobacterium tuberculosis (Mtb) to currently available fluoroquinolones (FQs), namely ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), renders the treatment of TB infections less successful. In this study, we aimed to evaluate the susceptibility and intracellular killing assay of Mtb to next-generation FQs in vitro and determine the correlation of FQs resistance and newly detected mutations in gyrB by molecular docking. Methods: Antimicrobial susceptibility test was performed to determine the minimum inhibitory concentrations (MICs) of six FQs, including currently available FQs (OFX, LFX, and MFX) and next-generation FQs, i.e., sitafloxacin (SFX), finafloxacin (FIN) and delafloxacin (DFX) against Mtb clinical isolates obtained in 2015 and 2022, respectively. Quinolone-resistance-determining regions of gyrA and gyrB were subjected to DNA sequencing and the correlation of FQs resistance and new mutations in gyrB were determined by molecular docking. Furthermore, the intracellular antibacterial activity of the six FQs against Mtb H37Rv in THP-1 cells was evaluated. Results: SFX exhibited the highest antibacterial activity against Mtb isolates (MIC90 = 0.25 µg/mL), whereas DFX and OFX exhibited comparable activity (MIC90 = 8 µg/mL). A statistically significant difference was observed among the MICs of the new generation FQs (SFX, P = 0.002; DFX, P = 0.008). Additionally, a marked increase in MICs was found in strains isolated in 2022 compared with those isolated in 2015. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A. Cross-resistance rate between SFX and MFX was 40.6 % (26/64). At a concentration of 1 µg/mL, SFX exhibited high intracellular antibacterial activity (96.6 % ± 1.5 %) against the Mtb H37Rv, comparable with that of MFX at a concentration of 2 µg/mL. Conclusion: SFX exhibits the highest inhibitory activity against Mtb in vitro and THP-1 cell lines, which exhibits partial-cross resistance with MFX. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A.Our findings provide crucial insights into the potential clinical application of SFX and DFX in the treatment of Mtb infections.

CD300ld on neutrophils is required for tumour-driven immune suppression.

The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy1,2. Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance2-4. Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy.

Operando Studies of Electrochemical Denitrogenation and Its Mitigation of N-Doped Carbon Catalysts in Alkaline Media.

N-doped carbons (NCs) have excellent electrocatalytic performance in oxygen reduction reaction, particularly in alkaline conditions, showing great promise of replacing commercial Pt/C catalysts in fuel cells and metal-air batteries. However, NCs are vulnerable when biased at high potentials, which suffer from denitrogenation and carbon corrosion. Such material degradation drastically undermines the activity, yet its dynamic evolution in response to the applied potentials is challenging to examine experimentally. In this work, we used differential electrochemical mass spectroscopy coupled with an optimized cell and observed the dynamic behaviors of NCs under operando conditions in KOH electrolyte. The corrosion of carbon occurred at ca. 1.2 V vs RHE, which was >0.3 V below the measured onset potential of water oxidation. Denitrogenation proceeded in parallel with carbon corrosion, releasing both NO and NO2. Combined with the ex situ characterizations and density-functional theory calculations, we identified that the pyridinic nitrogen moieties were particularly in peril. Three denitrogenation pathways were also proposed. Finally, we demonstrated that transferring the oxidation reaction sites to the well-deposited metal hydroxide with optimized loading was effective in suppressing the N leaching. This work showed the dynamic evolution of NC under potential bias and might cast light on understanding and mitigating NC deactivation for practical applications.

Reconstructing Clonal Evolution-A Systematic Evaluation of Current Bioinformatics Approaches.

The accurate reconstruction of clonal evolution, including the identification of newly developing, highly aggressive subclones, is essential for the application of precision medicine in cancer treatment. Reconstruction, aiming for correct variant clustering and clonal evolution tree reconstruction, is commonly performed by tedious manual work. While there is a plethora of tools to automatically generate reconstruction, their reliability, especially reasons for unreliability, are not systematically assessed. We developed clevRsim-an approach to simulate clonal evolution data, including single-nucleotide variants as well as (overlapping) copy number variants. From this, we generated 88 data sets and performed a systematic evaluation of the tools for the reconstruction of clonal evolution. The results indicate a major negative influence of a high number of clones on both clustering and tree reconstruction. Low coverage as well as an extreme number of time points usually leads to poor clustering results. An underlying branched independent evolution hampers correct tree reconstruction. A further major decline in performance could be observed for large deletions and duplications overlapping single-nucleotide variants. In summary, to explore the full potential of reconstructing clonal evolution, improved algorithms that can properly handle the identified limitations are greatly needed.

A temporal-spectral value and shape change detection method integrating thematic index information and spectral band information.

Satellite imagery time series change detection methods are effective in avoiding pseudochange due to vegetation phenology to a certain extent. Traditional time series change detection methods use thematic indexes (e.g., NDVI, RVI) to obtain time series information for corresponding change detection. However, change detection methods using several thematic index time series may not make full use of other spectral band information in remotely sensed images and may still suffer from over- and under-detections. To address this challenge, a temporal-spectral value and shape change detection method integrating thematic index information and spectral band information (TISB) is proposed. Possible clouds and cloud shadowing phenomena are removed according to the changes in the spectral values of the remotely sensed images to avoid the generation of pseudochanges in clouds. The spectral and time series information is used to obtain change information from the value perspective, and then, further possible enhanced change regions from a shape perspective to obtain the final change detection results through the expectation-maximization (EM) method. Experiments with Landsat images have shown that the TISB method improves detection results by approximately 1-4% compared to the comparison method.

High-Rate Alkaline Water Electrolysis at Industrially Relevant Conditions Enabled by Superaerophobic Electrode Assembly.

Alkaline water electrolysis (AWE) is among the most developed technologies for green hydrogen generation. Despite the tremendous achievements in boosting the catalytic activity of the electrode, the operating current density of modern water electrolyzers is yet much lower than the emerging approaches such as the proton-exchange membrane water electrolysis (PEMWE). One of the dominant hindering factors is the high overpotentials induced by the gas bubbles. Herein, the bubble dynamics via creating the superaerophobic electrode assembly is optimized. The patterned Co-Ni phosphide/spinel oxide heterostructure shows complete wetting of water droplet with fast spreading time (≈300 ms) whereas complete underwater bubble repelling with 180° contact angle is achieved. Besides, the current collector/electrode interface is also modified by coating with aerophobic hydroxide on Ti current collector. Thus, in the zero-gap water electrolyzer test, a current density of 3.5 A cm-2 is obtained at 2.25 V and 85 °C in 6 m KOH, which is comparable with the state-of-the-art PEMWE using Pt-group metal catalyst. No major performance degradation or materials deterioration is observed after 330 h test. This approach reveals the importance of bubble management in modern AWE, offering a promising solution toward high-rate water electrolysis.

Kernel-Based Generalized Median Computation for Consensus Learning.

Computing a consensus object from a set of given objects is a core problem in machine learning and pattern recognition. One popular approach is to formulate it as an optimization problem using the generalized median. Previous methods like the Prototype and Distance-Preserving Embedding methods transform objects into a vector space, solve the generalized median problem in this space, and inversely transform back into the original space. Both of these methods have been successfully applied to a wide range of object domains, where the generalized median problem has inherent high computational complexity (typically NP-hard) and therefore approximate solutions are required. Previously, explicit embedding methods were used in the computation, which often do not reflect the spatial relationship between objects exactly. In this work we introduce a kernel-based generalized median framework that is applicable to both positive definite and indefinite kernels. This framework computes the relationship between objects and its generalized median in kernel space, without the need of an explicit embedding. We show that the spatial relationship between objects is more accurately represented in kernel space than in an explicit vector space using easy-to-compute kernels, and demonstrate superior performance of generalized median computation on datasets of three different domains. A software toolbox resulting from our work is made publicly available to encourage other researchers to explore the generalized median computation and applications.

Enzymatic modification and adsorption of hydrophobic zein proteins on lactic acid bacteria stabilize Pickering emulsions.

The effect of enzymatic and physical modifications of the surface of two different strains from lactic acid bacteria, Lactobacillus rhamnosus (LGG) and Lactobacillus delbruekii subs. lactis ATCC 4797 (LBD), to stabilize medium-chain triglyceride (MCT) oil based Pickering emulsions were investigated. A section of cell wall degrading enzymes, lysozyme from chicken egg white and human, lysostaphin, mutanolysin from Streptomyces globisporus and proteinase k and the hydrophobic protein zein were used for enzymatic and physical surface modifications. Cell surface modifications were characterized by optical microscopy, scanning electron cryo-microscopy (Cryo-SEM), transmission electron microscopy (TEM), microbial adhesion to hexadecane (MATH) test and zeta potential measurements. The modified cell hydrophobicity in terms of MATH values were increased (around four times) by the enzymatic and physical modifications for LBD and LGG compared to the control. Emulsions stabilized by modified bacterial cells showed higher stability in comparison with unmodified samples, especially for the samples modified with chicken egg lysozyme. Confocal microscopy revealed that the modified bacterial cells were absorbed at the interface between oil and water and preventing the oil particles from coalescence. Thus, modified bacterial cells can be used to formulate food-grade stable Pickering emulsions. Such Pickering emulsions can potentially be clean label alternatives to replace the conventional emulsion preparations.

A review on AI-based medical image computing in head and neck surgery.

Head and neck surgery is a fine surgical procedure with a complex anatomical space, difficult operation and high risk. Medical image computing (MIC) that enables accurate and reliable preoperative planning is often needed to reduce the operational difficulty of surgery and to improve patient survival. At present, artificial intelligence, especially deep learning, has become an intense focus of research in MIC. In this study, the application of deep learning-based MIC in head and neck surgery is reviewed. Relevant literature was retrieved on the Web of Science database from January 2015 to May 2022, and some papers were selected for review from mainstream journals and conferences, such as IEEE Transactions on Medical Imaging, Medical Image Analysis, Physics in Medicine and Biology, Medical Physics, MICCAI, etc. Among them, 65 references are on automatic segmentation, 15 references on automatic landmark detection, and eight references on automatic registration. In the elaboration of the review, first, an overview of deep learning in MIC is presented. Then, the application of deep learning methods is systematically summarized according to the clinical needs, and generalized into segmentation, landmark detection and registration of head and neck medical images. In segmentation, it is mainly focused on the automatic segmentation of high-risk organs, head and neck tumors, skull structure and teeth, including the analysis of their advantages, differences and shortcomings. In landmark detection, the focus is mainly on the introduction of landmark detection in cephalometric and craniomaxillofacial images, and the analysis of their advantages and disadvantages. In registration, deep learning networks for multimodal image registration of the head and neck are presented. Finally, their shortcomings and future development directions are systematically discussed. The study aims to serve as a reference and guidance for researchers, engineers or doctors engaged in medical image analysis of head and neck surgery.

Efficient expansion of mouse hematopoietic stem cells ex vivo by membrane anchored Angptl2.

Hematopoietic stem cell (HSC) transplantation represents an important curative therapy for numerous hematological and immune diseases. Many efforts have been applied to achieve attainable ex vivo HSC expansion. We previously showed that angiopoietin-like proteins 2 (Angptl2) binds and activates the immune inhibitory receptor human leukocyte immunoglobulin (Ig)-like receptor B2 (LILRB2) to support the expansion of HSC. However, soluble Angptl2 is unstable and the downstream signaling would be attenuated by ligand-binding triggered receptor endocytosis, compromising the potential of Angptl2 to expand HSCs. We proposed that membrane anchored Angptl2 will overcome these limitations. In this study, we constructed the C-terminal and N-terminal anchored membrane Angptl2 (Cm-Angptl2 and Nm-Angptl2) by adding a transmembrane domain at the C-terminal or an anchor sequence at the N-terminal respectively. Both forms of Angptl2 showed efficient expression on the surface of feeder cells. Nm-Angptl2, but not Cm-Angptl2, induces a potent activation of LILRB2 reporter, indicating the fibronectin (FBN) domain at the C-terminus of Angptl2 is essential to stimulate LILRB2 signaling. Compared to soluble Angptl2, Nm-Angptl2 displays higher activities to activate LILRB2 reporter, and to promote the expansion of mouse HSCs as determined by transplantation and limiting dilution assay. Our study revealed the importance of FBN domain for Angptl2 to activate LILRB2 and demonstrated that Nm-Angptl2 have enhanced activities than the soluble protein in LILRB2 activation and HSC expansion, providing a strategy to explore the mode of ligand induced receptor signaling, and an optimized approach to expand HSCs ex vivo.

Hierarchical Random Walker Segmentation for Large Volumetric Biomedical Images.

The random walker method for image segmentation is a popular tool for semi-automatic image segmentation, especially in the biomedical field. However, its linear asymptotic run time and memory requirements make application to 3D datasets of increasing sizes impractical. We propose a hierarchical framework that, to the best of our knowledge, is the first attempt to overcome these restrictions for the random walker algorithm and achieves sublinear run time and constant memory complexity. The goal of this framework is- rather than improving the segmentation quality compared to the baseline method- to make interactive segmentation on out-of-core datasets possible. The method is evaluated quantitatively on synthetic data and the CT-ORG dataset where the expected improvements in algorithm run time while maintaining high segmentation quality are confirmed. The incremental (i.e., interaction update) run time is demonstrated to be in seconds on a standard PC even for volumes of hundreds of gigabytes in size. In a small case study the applicability to large real world from current biomedical research is demonstrated. An implementation of the presented method is publicly available in version 5.2 of the widely used volume rendering and processing software Voreen (https://www.uni-muenster.de/Voreen/).