Transformer for low concentration image denoising in magnetic particle imaging.

OBJECTIVE: Magnetic particle imaging (MPI) is an emerging tracer-based in vivo imaging technology. The use of MPI at low Superparamagnetic Iron Oxide Nanoparticle (SPION) concentrations has the potential to be a promising area of clinical application due to the inherent safety for humans. However, low tracer concentrations reduce the signal-to-noise ratio (SNR) of the magnetization signal, leading to severe noise artifacts in the reconstructed MPI images. Hardware improvements have high complexity, while traditional methods lack robustness to different noise levels, making it difficult to improve the quality of low concentration MPI images. APPROACH: Here, we propose a novel deep learning method for MPI image denoising and quality enhancing based on a sparse lightweight transformer model. The proposed residual-local transformer structure reduces model complexity to avoid overfitting, in which an information retention block facilitates feature extraction capabilities for the image details. Besides, we design a noisy concentration dataset to train our model. Then, we evaluate our method with both simulated and real MPI image data. MAIN RESULTS: Simulation experiment results show that our method can achieve the best performance compared with the existing deep learning methods for MPI image denoising. More importantly, our method is effectively performed on the real MPI image of samples with an Fe concentration down to 67 µgFe/mL. SIGNIFICANCE: Our method provides great potential for obtaining high quality MPI images at low concentrations.

Sunflower-Inspired Superhydrophobic Surface with Composite Structured Microcone Array for Anisotropy Liquid/Ice Manipulation.

Precisely controlling the directional motion trajectories of droplets on anisotropic 3D functional surfaces has great application potential in self-cleaning, drug delivery, and droplet power generation, but it also faces huge challenges. Herein, inspired by the microcone structure in the heart of sunflowers, a nanoneedle-modified microcone array surface (NMAS) is reported. The surface is created using a combination of nanosecond laser direct engraving and electroforming and is subsequently fluorinated. Through programmable control of the laser spot, the geometric parameters and inclination angle of the microcone can be quickly and finely adjusted, thereby achieving precise control of the droplet bouncing trajectory. The results show that droplets can achieve programmable multiple bouncing behaviors on patterned functional surfaces, including gravity-defying hopping and directional water transport. It is worth noting that this functional surface has delayed freezing and anti-freezing effects. Furthermore, this functional surface has a wide range of potential applications, including surface self-cleaning, droplet capture, and droplet-based chemical microreactions, especially in the field of anti-icing operations. This opens up a new way for the directional transport of droplets on biomimetic functional surfaces.

Antibiotic-induced severe cutaneous adverse reactions: a single-center retrospective study over ten years.

Objective: Severe cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs. Methods: We analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out. Results: Among 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups. Conclusion: The identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

Five-Year Outcomes of Bioresorbable Stent Therapy for Coronary Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.

Fabrication of high internal phase emulsions (HIPEs) using pea protein isolate-hyaluronic acid-tannic acid complexes: Application of curcumin-loaded HIPEs as edible inks for 3D food printing.

Pea protein isolate (PPI)-hyaluronic acid (HA)-tannic acid (TA) ternary complexes were assembled using non-covalent interactions, their potential application in 3D printing and delivery of curcumin were investigated. As the HA-to-TA ratio in the complexes changed from 1:0 to 0:1, the oil-water interfacial tension first decreased and then increased, and the secondary structure of the proteins changed. The composition of the complexes (HA-to-TA ratio) was optimized to produce high internal phase emulsions (HIPEs) containing small uniform oil droplets with good storage and thermal stability. When the HA to TA ratio is 7:1 (P-H7-T1), HIPEs exhibited better viscosity, viscoelasticity, and thixotropy, which contributed to its preferable 3D printing. Moreover, curcumin-loaded HIPEs stabilized by P-H7-T1 showed a high lipid digestibility (≈101%) and curcumin bioaccessibility (≈79%). In summary, the PPI-HA-TA-stabilized HIPEs have good potential to be 3D-printable materials that could be loaded with bioactive components.

Highly exposed metal atomic active sites in Al2O3/CoNC: Modify reaction pathways by coupling oxygen species.

The catalytic oxidation of formaldehyde (HCHO) at ambient temperature is a highly efficient, cost-effective and environmentally friendly approach for formaldehyde removal. Reactive oxygen (O*) and reactive hydroxyl groups (OH*) are the main active species in the catalytic oxidation reaction of HCHO. Therefore, it is crucial to design catalysts that can simultaneously enhance the surface concentrations of O* and OH*, thereby improving their overall catalytic performance. The present study aimed to design an Al2O3/CoNC catalyst featuring layered carbon nitride coupled with metal oxides possessing domain-limited cobalt (Co) metal active sites, to efficiently remove HCHO (≈100 %, 100 ppm, RH=50 %, GSHV=20,000 mL/(g h)) and ensure stability (more than 90 % formaldehyde removal within 450 h) at ambient temperature. The characterization revealed that the interaction between Al2O3-supported metal and CoNC resulted in enhanced confinement of Co, leading to a higher abundance of edge structures exposing more active sites. Additionally, the presence of highly dispersed Co-NX active sites and increased oxygen vacancies effectively facilitated the adsorption and activation processes of HCHO and O2, as well as the adsorption and desorption dynamics of intermediates during the reaction. These factors collectively contributed to an improved catalytic activity. The results of in situ infrared spectroscopy revealed that the catalyst improved the adsorption and activation of O2 and H2O, leading to the rapid generation of substantial amounts of O* and OH*. This synergistic interaction between Al2O3 and CoNC plays a crucial role in the sustained production of O* and OH*, promoting efficient of intermediate decomposition, and ensuring excellent catalytic activity and stability for HCHO.

Copper-loaded Milk-Protein Derived Microgel Preserves Cardiac Metabolic Homeostasis After Myocardial Infarction.

Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material-derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk-derived protein, is screened out as Cu2+ carrier through molecular-docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI-induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic-modulating biomaterials for ischemic cardiomyopathy therapy.

Development of pea protein nanoparticle/hydrolyzed rice glutelin fibril emulsion gels for encapsulation of curcumin.

The potential of using emulsion gels stabilized by binary plant protein nanoparticle mixtures for the encapsulation and delivery of lipophilic nutraceuticals was evaluated. The particle characteristics, physical stability, water diffusivity, microrheology, large amplitude oscillating shear (LAOS) properties, and in vitro digestion of emulsion gels prepared by different ratios of hydrolyzed rice glutelin fibrils (HRGFs) and pea protein nanoparticle (PNP) were characterized. The emulsion gel with P/H = 2:1 (0.84 µm) exhibited the best storage stability and freeze-thaw stability, as seen by the smaller oil droplet size (1.02 and 1.42 µm, respectively). Low-field pulsed NMR indicated that the majority of water in samples was highly mobile. All the samples were predominantly elastic-like materials. The P/H 2:1 emulsion gel had the lowest FI value (6.21 × 10-4 Hz), the highest MVI value (5.57 s/nm2), G'/ G″ values and enclosed area, showing that it had denser 3D network structures, higher stiffness values, and a high sensitivity to changes in strain. Additionally, P/H 2:1 emulsion gel had a relatively high lipid digestibility (96.1 %), curcumin bioaccessibility (58.9 %), and curcumin stability (94.2 %). This study showed that emulsion gels stabilized by binary protein nanoparticle mixtures (PNP/HRGF) have potential as edible delivery systems for lipophilic nutraceuticals.

Research hotspots and trends of spinal cord stimulation for neuropathic pain: a bibliometric analysis from 2004 to 2023.

The purpose of this study is to systematically analyze the development trend, research hotspots, and future development direction on the treatment of neuropathic pain (NP) with spinal cord stimulation through bibliometric method. We extracted the literature related to the treatment of NP with spinal cord stimulation from January 2004 to December 2023 from the Web of Science database. As a result, a total of 264 articles were retrieved. By analyzing the annual published articles, authors, countries, institutions, journals, co-cited literature, and keywords, we found that the count of publication in this field has been experiencing an overall growth, and the publications within the past 5 years accounted for 42% of the total output. Experts from the United States and the UK have made significant contributions in this field and established a stable collaborative team, initially establishing an international cooperation network. Pain is the frequently cited journal in this field. The study on spinal cord stimulation therapy for NP especially the study on spinal cord stimulation therapy for back surgery failure syndrome (FBSS) and its potential mechanisms are the research hotspots in this field, while the study on novel paradigms such as high-frequency spinal cord stimulation and spinal cord burst stimulation represents the future development directions. In short, spinal cord stimulation has been an effective treatment method for NP. The novel paradigms of spinal cord stimulation are the key point of future research in this field.

First-trimester hemoglobin, haptoglobin genotype, and risk of gestational diabetes mellitus in a retrospective study among Chinese pregnant women.

BACKGROUND: This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. METHODS: This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. RESULTS: Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. CONCLUSION: Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.

Application prospects of the 2BS cell-adapted China fixed rabies virus vaccine strain 2aG4-B40.

BACKGROUND: Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. METHODS AND RESULTS: The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). CONCLUSIONS: In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.

A greedy regularized block Kaczmarz method for accelerating reconstruction in magnetic particle imaging.

Objective.Magnetic particle imaging (MPI) is an emerging medical tomographic imaging modality that enables real-time imaging with high sensitivity and high spatial and temporal resolution. For the system matrix reconstruction method, the MPI reconstruction problem is an ill-posed inverse problem that is commonly solved using the Kaczmarz algorithm. However, the high computation time of the Kaczmarz algorithm, which restricts MPI reconstruction speed, has limited the development of potential clinical applications for real-time MPI. In order to achieve fast reconstruction in real-time MPI, we propose a greedy regularized block Kaczmarz method (GRBK) which accelerates MPI reconstruction.Approach.GRBK is composed of a greedy partition strategy for the system matrix, which enables preprocessing of the system matrix into well-conditioned blocks to facilitate the convergence of the block Kaczmarz algorithm, and a regularized block Kaczmarz algorithm, which enables fast and accurate MPI image reconstruction at the same time.Main results.We quantitatively evaluated our GRBK using simulation data from three phantoms at 20 dB, 30 dB, and 40 dB noise levels. The results showed that GRBK can improve reconstruction speed by single orders of magnitude compared to the prevalent regularized Kaczmarz algorithm including Tikhonov regularization, the non-negative Fused Lasso, and wavelet-based sparse model. We also evaluated our method on OpenMPIData, which is real MPI data. The results showed that our GRBK is better suited for real-time MPI reconstruction than current state-of-the-art reconstruction algorithms in terms of reconstruction speed as well as image quality.Significance.Our proposed method is expected to be the preferred choice for potential applications of real-time MPI.

Re-Engineering Fungal Nonribosomal Peptide Synthetases by Module Dissection and Duplicated Thiolation Domains.

Unnatural product (uNP) nonribosomal peptides promise to be a valuable source of pharmacophores for drug discovery. However, the extremely large size and complexity of the nonribosomal peptide synthetase (NRPS) enzymes pose formidable challenges to the production of such uNPs by combinatorial biosynthesis and synthetic biology. Here we report a new NRPS dissection strategy that facilitates the engineering and heterologous production of these NRPSs. This strategy divides NRPSs into "splitting units", each forming an enzyme subunit that contains catalytically independent modules. Functional collaboration between the subunits is then facilitated by artificially duplicating, at the N-terminus of the downstream subunit, the linker - thiolation domain - linker fragment that is resident at the C-terminus of the upstream subunit. Using the suggested split site that follows a conserved motif in the linker connecting the adenylation and the thiolation domains allows cognate or chimeric splitting unit pairs to achieve productivities that match, and in many cases surpass those of hybrid chimeric enzymes, and even those of intact NRPSs, upon production in a heterologous chassis. Our strategy provides facile options for the rational engineering of fungal NRPSs and for the combinatorial reprogramming of nonribosomal peptide production.

Association between circulating levels of unsaturated fatty acids and risk for prediabetes in the NHANES 2003-2004 and 2011-2012.

AIMS: This study aimed to investigate the association between serum levels of common and uncommon unsaturated fatty acids and prediabetes risk. METHODS: Data were collected from the National Health and Nutrition Examination Survey for 2003-2004 and 2011-2012. Weighted proportional and multivariate logistic regression analyses were performed to assess the association of serum PUFAs and MUFAs with prediabetes risk after adjusting for potential confounders. RESULTS: A total of 3575 individuals were enrolled in this study. Serum levels of PUFAs EPA (20:5 n3) and GLA (18:3 n6) were associated with increased prediabetes risk (EPA (20:5 n3): OR = 1.878, 95% CI: 1.177-2.996, Ptrend = 0.002; GLA (18:3 n6): 1.702, 95% CI: 1.140-2.541, Ptrend = 0.016). The MUFAs PA (16:1 n7) and EA (20:1 n9) were associated with the risk of prediabetes (OR in quintile5: PA (16:1 n7): 1.780, 95% CI: 1.056-3.001, Ptrend = 0.003; EA (20:1 n9): 0.587, 95% CI: 0.347-0.994, Ptrend = 0.010). Moreover, nonlinear analysis revealed that serum levels of EPA (20:5 n3) and EA (20:1 n-9) were nonlinearly associated with prediabetes risk. CONCLUSION: Some serum n-3 PUFAs are positively associated with prediabetes, several serum n-6 PUFAs are inversely associated with prediabetes. Regulating individual serum USFA levels may help prevent prediabetes, thereby providing evidence for clinical and nutritional practices.

An in vivo "turning model" reveals new RanBP9 interactions in lung macrophages.

The biological functions of the scaffold protein Ran Binding Protein 9 (RanBP9) remain elusive in macrophages or any other cell type where this protein is expressed together with its CTLH (C-terminal to LisH) complex partners. We have engineered a new mouse model, named RanBP9-TurnX, where RanBP9 fused to three copies of the HA tag (RanBP9-3xHA) can be turned into RanBP9-V5 tagged upon Cre-mediated recombination. We created this model to enable stringent biochemical studies at cell type specific level throughout the entire organism. Here, we have used this tool crossed with LysM-Cre transgenic mice to identify RanBP9 interactions in lung macrophages. We show that RanBP9-V5 and RanBP9-3xHA can be both co-immunoprecipitated with the known members of the CTLH complex from the same whole lung lysates. However, more than ninety percent of the proteins pulled down by RanBP9-V5 differ from those pulled-down by RanBP9-HA. The lung RanBP9-V5 associated proteome includes previously unknown interactions with macrophage-specific proteins as well as with players of the innate immune response, DNA damage response, metabolism, and mitochondrial function. This work provides the first lung specific RanBP9-associated interactome in physiological conditions and reveals that RanBP9 and the CTLH complex could be key regulators of macrophage bioenergetics and immune functions.

Age-dependent molecular variations in osteosarcoma: implications for precision oncology across pediatric, adolescent, and adult patients.

Background: Osteosarcoma is a leading subtype of bone tumor affecting adolescents and adults. Comparative molecular characterization among different age groups, especially in pediatric, adolescents and adults, is scarce. Methods: We collected samples from 194 osteosarcoma patients, encompassing pediatric, adolescent, and adult cohorts. Genomic analyses were conducted to reveal prevalent mutations and compare molecular features in pediatric, adolescent, and adult patients. Results: Samples from 194 osteosarcoma patients across pediatric to adult ages were analyzed, revealing key mutations such as TP53, FLCN, NCOR1, and others. Children and adolescents showed more gene amplifications and HRD mutations, while adults had a greater Tumor Mutational Burden (TMB). Mutations in those over 15 were mainly in cell cycle and PI3K/mTOR pathways, while under 15s had more in cell cycle and angiogenesis with higher VEGFA, CCND3, TFEB mutations. CNV patterns varied with age: VEGFA and XPO5 amplifications more in under 25s, and CDKN2A/B deletions in over 25s. Genetic alterations in genes like MCL1 and MYC were associated with poor prognosis, with VEGFA mutations also indicating worse outcomes. 58% of patients had actionable mutations, suggesting opportunities for targeted therapies. Age-specific patterns were observed, with Multi-TKI mutations more common in younger patients and CDK4/6 inhibitor mutations in adults, highlighting the need for personalized treatment approaches in osteosarcoma. In a small group of patients with VEGFR amplification, postoperative treatment with multi-kinase inhibitors resulted in a PR in 3 of 13 cases, especially in patients under 15. A significant case involved a 13-year-old with a notable tumor size reduction achieving PR, even with other genetic alterations present in some patients with PD. Conclusion: This study delineates the molecular differences among pediatric, adolescent, and adult osteosarcoma patients at the genomic level, emphasizing the necessity for precision diagnostics and treatment strategies, and may offer novel prognostic biomarkers for patients with osteosarcoma. These findings provide a significant scientific foundation for the development of individualized treatment approaches tailored to patients of different age groups.

Siglec-6 as a therapeutic target for cell migration and adhesion in chronic lymphocytic leukemia.

Siglec-6 is a lectin receptor with restricted expression in the placenta, mast cells and memory B-cells. Although Siglec-6 is expressed in patients with chronic lymphocytic leukemia (CLL), its pathophysiological role has not been elucidated. We describe here a role for Siglec-6 in migration and adhesion of CLL B cells to CLL- bone marrow stromal cells (BMSCs) in vitro and compromised migration to bone marrow and spleen in vivo. Mass spectrometry analysis revealed interaction of Siglec-6 with DOCK8, a guanine nucleotide exchange factor. Stimulation of MEC1-002 CLL cells with a Siglec-6 ligand, sTn, results in Cdc42 activation, WASP protein recruitment and F-actin polymerization, which are all associated with cell migration. Therapeutically, a Siglec-6/CD3-bispecific T-cell-recruiting antibody (T-biAb) improves overall survival in an immunocompetent mouse model and eliminates CLL cells in a patient derived xenograft model. Our findings thus reveal a migratory role for Siglec-6 in CLL, which can be therapeutically targeted using a Siglec-6 specific T-biAb.