LINC02454 promotes thyroid carcinoma progression via upregulating HMGA2 through CREB1.

Thyroid carcinoma (THCA) is the most common malignancy in the endocrine system. Long intergenic non-coding RNA 2454 (LINC02454) exhibits an HMGA2-like expression pattern, but their relationship and roles in THCA are largely unknown. The present purpose was to delineate the roles of LINC02454 in THCA progression and its molecular mechanisms. We collected THCA tissues from patients and monitored patient survival. THCA cell colony formation, migration, and invasion were evaluated. Metastasis was evaluated by examining EMT markers through Western blotting. Gene interaction was determined with ChIP, RIP, RNA pull-down, and luciferase activity assays. A mouse model of a subcutaneous tumor was used to determine the activity of LINC02454 knockdown in vivo. We found that LINC02454 was highly expressed in THCA, and its upregulation was associated with poor survival. The knockdown of LINC02454 repressed colony formation, migration, and invasion. Moreover, loss of LINC02454 inhibited tumor growth and metastasis in mice. HMGA2 promoted LINC02454 transcription via binding to the LINC02454 promoter, and silencing of HMGA2 suppressed malignant behaviors through downregulation of LINC02454. HMGA2 was a novel functional target of LINC02454 in THCA cells, and knockdown of LINC02454-mediated anti-tumor effects was reversed by HMGA2 overexpression. Mechanically, LINC02454 promoted CREB1 phosphorylation and nuclear translocation, and CREB1 was subsequently bound to the HMGA2 promoter to facilitate its expression. LINC02454 cis-regulates HMGA2 transcription via facilitating CREB1 phosphorylation and nuclear translocation, and, in turn, HMGA2 promotes LINC02454 expression, thus accelerating thyroid carcinoma progression. Our results support therapeutic targets of LINC02454 and HMGA2 for THCA.

Optimized MLPA workflow for spinal muscular atrophy diagnosis: identification of a novel variant, NC_000005.10:g.(70919941_70927324)del in isolated exon 1 of SMN1 gene through long-range PCR.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal recessive hereditary neuromuscular disease caused by survival motor neuron 1 (SMN1) gene deletion or mutation. Homozygous deletions of exon 7 in SMN1 result in 95% of SMA cases, while the remaining 5% are caused by other pathogenic variants of SMN1. METHODS: We analyzed two SMA-suspected cases that were collected, with no SMN1 gene deletion and point mutation in whole-exome sequencing. Exon 1 deletion of the SMN gene was detected using Multiplex ligation-dependent probe amplification (MLPA) P021. We used long-range polymerase chain reaction (PCR) to isolate the SMN1 template, optimized-MLPA P021 for copy number variation (CNV) analysis within SMN1 only, and validated the findings via third-generation sequencing. RESULTS: Two unrelated families shared a genotype with one copy of exon 7 and a novel variant, g.70919941_70927324del, in isolated exon 1 of the SMN1 gene. Case F1-II.1 demonstrated no exon 1 but retained other exons, whereas F2-II.1 had an exon 1 deletion in a single SMN1 gene. The read coverage in the third-generation sequencing results of both F1-II.1 and F2-II.1 revealed a deletion of approximately 7.3 kb in the 5' region of SMN1. The first nucleotide in the sequence data aligned to the 7385 bp of NG_008691.1. CONCLUSION: Remarkably, two proband families demonstrated identical SMN1 exon 1 breakpoint sites, hinting at a potential novel mutation hotspot in Chinese SMA, expanding the variation spectrum of the SMN1 gene and corroborating the specificity of isolated exon 1 deletion in SMA pathogenesis. The optimized-MLPA P021 determined a novel variant (g.70919941_70927324del) in isolated exon 1 of the SMN1 gene based on long-range PCR, enabling efficient and affordable detection of SMN gene variations in patients with SMA, providing new insight into SMA diagnosis to SMN1 deficiency and an optimized workflow for single exon CNV testing of the SMN gene.

Analytical validation of the amplification refractory mutation system polymerase chain reaction-capillary electrophoresis assay to diagnose spinal muscular atrophy.

OBJECTIVES: Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous deletion and compound heterozygous mutations in survival motor neuron 1 (SMN1), with severity tied to the copy number of survival motor neuron 2 (SMN2). This study aimed to develop a rapid and comprehensive method for the diagnosis of SMA. METHODS: A total of 292 children with clinically suspected SMA and 394 family members were detected by the amplification refractory mutation system polymerase chain reaction-capillary electrophoresis (ARMS-PCR-CE) method, which targeted 19 reported mutations, and the results were compared with those in multiplex ligation-dependent probe amplification (MLPA). Individuals with identified point mutations were further confirmed by SMN1 long-range PCR and Sanger sequencing. RESULTS: A total of 202 children with SMA, 272 carriers, and 212 normal individuals were identified in this study. No difference was found in the R-value distribution of exons 7 and 8 in SMN1 and SMN2 among these cohorts, with coefficients of variation consistently below 0.08. To detect exon 7 and 8 copy numbers in SMN1 and SMN2, the ARMS-PCR-CE results were concordant with those of MLPA. Approximately 4.95 % (10/202) of the study patients had compound heterozygous mutations. CONCLUSIONS: The ARMS-PCR-CE assay is a comprehensive, rapid, and accurate diagnostic method for SMA that simultaneously detects copy numbers of exons 7 and 8 in SMN1/SMN2, as well as 19 point mutations in SMN1 and 2 enhancers in SMN2. This approach can effectively reduce the time frame for diagnosis, facilitating early intervention and preventing birth defects.

Efficacy and safety of salbutamol in treatment of children with later-onset spinal muscular atrophy. / ç¡«é ¸æ²™ä¸èƒºé†‡æ²»ç–—æ™šå‘åž‹è„Šé«“æ€§è‚ŒèŽç¼©ç—‡æ‚£å„¿ä¸´åºŠç–—æ•ˆåŠå®‰å ¨æ€§è§‚å¯Ÿ.

OBJECTIVES: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). METHODS: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. RESULTS: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. CONCLUSIONS: Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.

Serum neurofilament light chain in adult and pediatric patients with myelin oligodendrocyte glycoprotein antibody-associated disease: Correlation with relapses and seizures.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) causes major disability as a consequence of recurrent demyelinating events and neuronal loss. Biomarkers identifying different phenotypes of recurrence or tissue damage might be useful to guide individualized therapy. Herein, we evaluated serum neurofilament light chain (sNfL) as a potential biomarker in both adult and pediatric MOGAD patients. Forty-nine patients with MOGAD (37 adults, 12 children) and 71 healthy controls (HCs) (56 adults, 15 children) were enrolled prospectively from September 2019 to April 2021 at the Third Affiliated Hospital of Sun Yat-sen University and the Children's Hospital, Zhejiang University School of Medicine. sNfL levels were determined using ultrasensitive single-molecule array assay and correlated with clinical parameters. The sNfL levels in MOGAD adults in a relapsed state (median: 31.0 pg/ml) were higher than those in a remission state (8.1 pg/ml, p = 0.001) and in HC adults (10.3 pg/ml, p = 0.004). Similar results were observed in children (relapse: 46.8 pg/ml vs. remission: 13.1 pg/ml, p = 0.001; and vs. HCs: 8.2 pg/ml, p = 0.007) sNfL levels were correlated with recent relapses within 60 days (multivariate: ß = 2.02, p = 0.003), seizures (multivariate: ß = 2.50, p = 0.021) and brain lesions on magnetic resonance imaging (MRI) of a recent relapse (multivariate: ß = 1.72, p = 0.012). Our study showed that sNfL levels are beneficial for identifying recent relapses and seizures and suggest that adult and pediatric MOGAD patients had similar sNfL levels.

Stress granules in the spinal muscular atrophy and amyotrophic lateral sclerosis: The correlation and promising therapy.

Increasing genetic and biochemical evidence has broadened our view of the pathomechanisms that lead to Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS), two fatal neurodegenerative diseases with similar symptoms and causes. Stress granules are dynamic cytosolic storage hubs for mRNAs in response to stress exposures, that are evolutionarily conserved cytoplasmic RNA granules in somatic cells. A lot of previous studies have shown that the impaired stress granules are crucial events in SMA/ALS pathogenesis. In this review, we described the key stress granules related RNA binding proteins (SMN, TDP-43, and FUS) involved in SMA/ALS, summarized the reported mutations in these RNA binding proteins involved in SMA/ALS pathogenesis, and discussed the mechanisms through which stress granules dynamics participate in the diseases. Meanwhile, we described the applications and limitation of current therapies targeting SMA/ALS. We futher proposed the promising targets on stress granules in the future therapeutic interventions of SMA/ALS.

Decreased abundance of Akkermansia after adrenocorticotropic hormone therapy in patients with West syndrome.

BACKGROUND: Infants suffer from a severe epileptic encephalopathy known as West syndrome (WS). Treatment with adrenocorticotropic hormone (ACTH) indicates the involvement of the gut-brain axis in WS. Several pieces of evidence show the communication of the gut microbiota (GM) with the brain via the hypothalamic-pituitary-adrenal axis (HPA axis) and blood cytokines. This study aimed at (1) determining the GM diversity in infants having WS and (2) comparing the results of infants having WS with those of the healthy infants and also in the patients with WS before and after the ACTH therapy. RESULTS: In this study, 29 infants with WS and 29 healthy infants aged 3-13 months were recruited. Fecal samples were collected, and DNA was extracted and sequenced on the Illumina MiSeq platform. Kruskal-Wallis rank-sum test was used to analyze the between-group differences in the Chao1 index, Shannon index, and the abundances of GM at different taxonomy levels. R software was used to plot the graphs. The top five dominant GM genera between patients with WS and healthy infants showed no significant differences. However, the relative abundance of genus Akkermansia was observed to be significantly (P = 0.011) higher in the BT group than in the HC group and AT group. After 2 weeks of ACTH therapy, the relative abundance of Akkermansia significantly (P = 0.003) decreased. CONCLUSION: The relative abundance of Akkermansia was observed to be significantly higher in patients with WS than that in healthy infants. However, the relationship between Akkermansia and WS pathogenesis needs to be clarified in further studies.

Novel EBV LMP1 C-terminal domain binding affibody molecules as potential agents for in vivo molecular imaging diagnosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) latent infection and is common in Southern China and Southeast Asia. The viral latent membrane proteins LMP1 and LMP2 are persistently expressed in NPC tissues; the cytoplasmic domain of LMP1 (LMP1 C-terminal) and LMP2A (LMP2A N-terminal) proteins is essential for maintenance of latency and can alter host cell signaling to facilitate tumor growth and progression. Thus, targeting LMP1 or LMP2 oncoprotein has been an increasing interest for diagnosis and targeted therapy of NPC. Affibody molecules, a new class of small-affinity engineered scaffold proteins, have demonstrated high potential for therapeutics, diagnostics, and biotechnological applications. More recently, radiolabelled HER2-specific affibody molecules have demonstrated to be useful in imaging of HER2 expressing tumor. In this study, we report three novel EBV LMP1 C-terminal (EBV LMP1-C) domain affibody molecules (ZLMP1-C15, ZLMP1-C114, and ZLMP1-C277) were selected by biopanning from a random-peptide displayed phage library and used for molecular imaging in tumor-bearing nude mice. Surface plasmon resonance (SPR), indirect immunofluorescence, and immunohistochemistry (IHC) clearly showed that all three selected affibody molecules have high affinity and specificity in binding to EBV LMP1 protein. Moreover, in vivo tumor imaging revealed that Dylight-755-labeled affibody molecules accumulated rapidly in tumor site after injection (1 h) and then were continuously maintained for 24 h in EBV-positive NPC xenograft mice model. In conclusion, our findings highlight the potential use of ZLMP1-C affibody molecules as tumor-specific molecular imaging agents of EBV-associated NPC.Key points• We screened three novel affibody molecules (ZLMP1-C15, ZLMP1-C114, and ZLMP1-C277) targeting EBV LMP1-C terminal domain• ZLMP1-C recognize the recombinant and native LMP1-C with high affinity and specificity• ZLMP1-C can be used for molecular imaging.

Epidemiological and virological characteristics of respiratory tract infections in children during COVID-19 outbreak.

BACKGROUND: To investigate the impact of protective measures and isolation on respiratory tract infections in children during the COVID-19 outbreak. METHODS: We extracted data on outpatient visits and respiratory infection visits, and tests of respiratory viruses (adenovirus (ADV), influenza A (FluA), influenza B (FluB) and respiratory syncytial virus (RSV)) from electronic healthcare records in Children's Hospital, Zhejiang University School of Medicine during the COVID-19 outbreak (January-April, 2020), compared with those in 2018 and 2019 during the same periods. RESULTS: We found that outpatient visits in January, 2020 was comparable with those in 2018 and 2019, but decreased by 59.9% (288,003 vs. 717,983) and 57.4% (288,003 vs. 676,704), respectively during the period of February-April, 2020, as compared with the same periods in 2018 and 2019. The total number of respiratory tract infections from January to April 2020 decreased by 65.7% (119,532 vs.348,762) and 59.0% (119,532 vs.291,557), respectively compared with the same periods in 2018 and 2019. The proportion of respiratory tract infections during the outbreak also dropped compared with the same periods in 2018 and 2019 (P<0.001). We also found significantly decreased number of completed tests for respiratory viruses and positive cases of ADV, FluA, FluB, and RSV during February-April, 2020. CONCLUSIONS: In this study, we found that outpatient visits and respiratory tract infections in children significantly decreased during COVID-19 outbreak. Adequate protective measures and isolation in children may help to prevent respiratory virus infections in children.

[Research advances in the biomarkers of brain damage in preterm infants].

While the survival rate of preterm infants has continually increased with the development of perinatal and neonatal monitoring techniques, the incidence of brain injury in preterm infants has been increasing, resulting in varying degrees of cognitive impairment and movement disorders. Measuring the biomarkers of brain damage is an important means to diagnose brain injury. The biomarkers can be divided into neuroglial damage markers, neuronal damage markers and other markers according to the features of injured cells. The biomarkers widely used in clinical practice include S100B protein, myelin basic protein and neuron-specific enolase. Recent studies have newly discovered a collection of markers that can suggest potential brain injury in preterm infants, such as glial fibrillary acidic protein, neurofilament light chain protein, α-II spectrin breakdown products, chemokines, melatonin and urinary metabolomics. These biomarkers can contribute to the early diagnosis and treatment of preterm brain injury, essential for improving neural development and prognosis. This article reviews the latest research advances in the biomarkers of preterm brain injury, in order to provide evidence for the early diagnosis and treatment of this condition.

Design of a high-numerical-aperture extreme ultraviolet lithography illumination system.

High-numerical-aperture (NA) anamorphic imaging projection objectives are the industrial choice for extreme ultraviolet lithography under the advanced technology node. The illumination system has to match the elliptical entrance pupil of the high-NA projector. In this paper, an illumination system suitable for a high-NA anamorphic projection objective is designed. The two-mirror relay system of the illumination system is designed by a two-stage process. The first-order initial configuration with spherical surfaces is calculated by a method based on matrix optics. Then after tilting and decentering the two spherical surfaces to eliminate obscuration, the two mirror surfaces are fitted into conic surfaces. To realize many different illumination modes, a facet mirror matching method based on combinatorial optimization is proposed to allocate the mapping relationship between the field and pupil facets under different illumination modes. Simulation results of the system illumination uniformity show the system can achieve high uniformity on the reticle under different illumination modes.

Sensitive and selective detection of Cu(II) ion: A new effective 1,8-naphthalimide-based fluorescence 'turn off' sensor.

The present study reports the development of a new 1,8-naphthalimide-based fluorescent sensor V for monitoring Cu(II) ions. The sensor exhibited pH independence over a wide pH range 2.52-9.58, and indicated its possible use for monitoring Cu(II) ions in a competitive pH medium. The sensor also showed high selectivity and sensitivity towards the Cu(II) ions over other competitive metal ions in DMSO-HEPES buffer (v/v, 1:1; pH 7.4) with a fluorescence 'turn off' mode of 79.79% observed. A Job plot indicated the formation of a 1:1 binding mode of the sensor with Cu(II) ions. The association constant and detection limit were 1.14 × 106  M-1 and 4.67 × 10-8 M, respectively. The fluorescence spectrum of the sensor was quenched due to the powerful paramagnetic nature of the Cu(II) ions. Potential application of this sensor was also demonstrated when determining Cu(II) ion levels in two different water samples.

Characterization of a highly Al3+ -selective fluorescence probe based on naphthalimide-Schiff base and its application to practical water samples.

A new fluorescent Al3+ -probe, N-allyl-4-[3,3'-((2-aminoethyl)azanediyl)-bis(N´-(2-hydroxybenzylidene)propanehy-drazide)]-1,8-naphthalimide (L), was designed and synthesized based on 1,8-naphthalimide. The probe L contains 1,8-naphthalimide moiety as the fluorophore and a Schiff base as the recognition group. The structure of L was determined by single crystal X-ray. L emission at 526 nm increased on addition of Al3+ under excitation wavelength at 350 nm. L exhibited high selectivity and sensitivity fluorescence emission towards to Al3+ in ethanol/Tris-HCl buffer solution (1:1, v/v, pH = 7.2) as compared with other tested metal ions. A good linearity with a correlation coefficient (R2 ) of 0.99 was observed in the concentration range 2-10 µM. The binding constant and the detection limit of L for Al3+ were calculated to 2.6 × 104  M-1 and 0.34 µM, respectively. The results of experiments that including Job plot, ultraviolet-visible (UV-Vis) light titration, fluorescence titration, ESI-MS and 1 H NMR titration, indicated a 1:1 stoichiometric complex between L and Al3+ . L was highly effective in monitoring Al3+ in real-life Yellow River and tap water samples.

Clinical characteristic comparison of low birth weight and very low birth weight preterm infants with neonatal necrotizing enterocolitis: a single tertiary center experience from eastern China.

PURPOSE: This study aims to understand the clinical characteristics of preterm neonatal necrotizing enterocolitis (NEC) to improve the medical management level. METHODS: The clinical characteristics of preterm NEC infants with low birth weight (LBW, ≥ 1500 g) and very low birth weight (VLBW, < 1500 g) were compared. Then, clinical information, including demographics, surgical interventions and morbidity, were collected. RESULTS: A total of 149 preterm NEC infants (60 with VLBW and 89 with LBW) were enrolled. Their median birth weight and gestational age were 1600 g and 31 weeks, respectively. Respiratory support and surfactant therapy were more frequent in VLBW infants (90% vs. 38% and 75% vs. 21.3%) than in LBW infants. In addition, 70.5% of these infants were fed by formula before the NEC occurred. Prematurity-associated morbidities were significantly higher in VLBW infants. Furthermore, 12.8% of all NEC infants died at discharge, and mortality was more prevalent in VLBW infants (21.7% vs. 6.7%). The most frequently received surgeries were enterostomy (n = 58), primary anastomosis (n = 42), and peritoneal drainage (n = 2). Multifocal, localized and pan-intestinal disease occurred in 77.5%, 19.6% and three infants, respectively. Furthermore, postoperative complications occurred more frequently in VLBW infants. CONCLUSION: The overall mortality was 12.8% for infants who had a larger mean gestational age and birth weight, when compared to that in developed countries. Higher rate of formula feeding might be an important risk factor for NEC development. Furthermore, mortality and morbidities, especially nutrition-associated complications, were more frequent in VLBW infants.

A Highly Selective and Sensitive Fluorescent Turn-on Probe for Al3+ Based on Naphthalimide Schiff Base.

A simple and highly selective aluminium ion fluorescent probe (N-n-butyl-4-[3,3'-((2-aminoethyl)azanediyl)bis(N'-(2-hydroxy-3-methoxybenzylidene)-propanehydrazide)]-1,8-naphthalimide) (P-1) employing 1,8-naphthalimide as the fluorophore group and Schiff base as the recognition group has been successfully synthesized and systemically characterized. The structure of probe P-1 has been established by single crystal X-ray. The photophysical properties of probe P-1 revealed that the values of the fluorescence quantum yield are higher in non-polar solvents than in polar solvents. Compared with the free P-1, the fluorescence intensity of P-1 shows a significant fluorescence enhancement in the presence of Al3+ without any significant interference from other cations and anions. In addition, from the UV-vis titration, fluorescence titration,Job's plot and 1H NMR spectra analysis, we could primarily confirm that three important coordinative sites of P-1 for Al3+ were from imine nitrogen and tertiary amine nitrogen and formed a 1:1 complex. The fluorescence intensity for the (P-1) showed a good linearity with the concentration of Al3+ in the range of 3.0-10.0 µM, with a detection limit of 8.65 × 10-8 M and a binding constant (Kb) of 4.95 × 104 M-1. It is worthy of note that the probe P-1 was successfully applied in detection of Al3+ in Yellow River and tap water samples.

Role of Lipocalin-2 in Thrombin-Induced Brain Injury.

BACKGROUND AND PURPOSE: Thrombin and lipocalin-2 (LCN2) contribute to intracerebral hemorrhage-induced brain injury. Thrombin-induced brain damage is partially through a thrombin receptor, protease-activated receptor-1. LCN2 is involved in cellular iron transport and neuroinflammation. This study investigated the role of LCN2 in thrombin-induced brain injury. METHODS: There were 3 parts in this study. First, male adult C57BL/6 wild-type or LCN2 knockout (LCN2 KO) mice had an intracaudate injection of thrombin (0.4 U) or saline. Second, LCN2 KO mice had an injection of thrombin (0.4 U) with recombinant mouse LCN2 protein (1 µg) into the right caudate. Third, protease-activated receptor-1 KO or wild-type mice had an intracaudate injection of thrombin or saline. All mice had T2-weighted magnetic resonance imaging and behavioral tests. Brains were used for histology, immunohistochemistry, and Western blotting. RESULTS: Intracerebral thrombin injection caused LCN2 upregulation and brain injury in mice. Thrombin-induced brain swelling, blood-brain barrier disruption, neuronal death, and neurological deficits were markedly less in LCN2 KO mice (P<0.05) and were exacerbated by exogenous LCN2 coinjection. In addition, thrombin injection resulted in less LCN2 expression and brain injury in protease-activated receptor-1 KO mice. CONCLUSIONS: Thrombin upregulates LCN2 through protease-activated receptor-1 activation and causes brain damage.

Role of Erythrocyte CD47 in Intracerebral Hematoma Clearance.

BACKGROUND AND PURPOSE: Enhancing hematoma clearance through phagocytosis may reduce brain injury after intracerebral hemorrhage. In the current study, we investigated the role of cluster of differentiation 47 (CD47) in regulating erythrophagocytosis and brain injury after intracerebral hemorrhage in nude mice. METHODS: This study was in 2 parts. First, male adult nude mice had an intracaudate injection of 30 µL saline, blood from male adult wild-type (WT) mice, or blood from CD47 knockout mice. Second, mice had an intracaudate injection of 30 µL CD47 knockout blood with clodronate or control liposomes. Clodronate liposomes were also tested in saline-injected mice. All mice then had magnetic resonance imaging to measure hematoma size and brain swelling. Brains were used for immunohistochemistry and Western blot. RESULTS: Erythrophagocytosis occurred in and around the hematoma. Injection of CD47 knockout blood resulted in quicker clot resolution, less brain swelling, and less neurological deficits compared with wild-type blood. Higher brain heme oxygenase-1 levels and more microglial activation (mostly M2 polarized microglia) at day 3 were found after CD47 knockout blood injection. Co-injection of clodronate liposomes, to deplete phagocytes, caused more severe brain swelling and less clot resolution. CONCLUSIONS: These results indicated that CD47 has a key role in hematoma clearance after intracerebral hemorrhage.