e14504 Background: Advanced melanoma remains therapeutically challenging due to drug resistance, metastasis, and an immunosuppressive tumor microenvironment (TME). Temozolomide (TMZ) has demonstrated antitumor effects in melanoma in combination regimes. MR001 is a CD4/TGF-β bispecific antibody, first-in-class and first-in-human drug (approved by NMPA, 2023LP01942), which simultaneously activates CD4⁺ T cells and inhibits TGF-β signaling, reprogramming TME by limiting Treg-mediated immunosuppression, facilitating antitumor immune response, and increasing drug permeability. Conventional PDX is a powerful translational tool, but it has a low success rate, a lengthy establishment time, and requires high cost. Our previous studies proved that Magnetically-Induced Cell (MagIC) technology can expedite the reconstruction of the TME and the establishment of PDX (MagIC-PDX). This study aims to assess the efficacy of MR001 + TMZ in advanced metastatic melanoma in MagIC-PDX models. Methods: Metastatic melanoma MagIC-PDX models were established using NSG mice (n = 12) from fresh sample donated by a multiple metastatic melanoma patient in our hospital. In parallel, a murine model with humanized CD4⁺ (hCD4) mice (n = 32) were randomized into four groups: control, TMZ, MR001, and MR001 + TMZ; according to the patient all mice were engrafted with magnetized GFP/luciferase-labeled B16F10-GL cells into bone, subcutaneous tissue, and peritoneum using MagIC technology. Treatment was administered for 2 weeks along with bioluminescence imaging. TME remodeling was analyzed by immunofluorescence and qPCR. Concordance between the MagIC-PDX model and the corresponding patient clinical features was assessed. Results: In MagIC murine metastasis models, tumors developed at (3.9 ± 1.79) days. In the MR001 + TMZ group, both metastatic tumor size, qPCR, and bioluminescence signal are significantly decreased compared with both monotherapy groups (P < 0.001) and the control group (P < 0.001). Pathological examination showed that immunofluorescence signals of type III collagen encapsulation and decreased tumoral cell presence in the MR001 + TMZ group (P < 0.001), consistent with an immunoreactive and drug-permeable TME. The MagIC-PDX model behavior corresponds to the patient tumor, and the response to the combination treatment showed similar results compared to the murine model. Conclusions: MR001 synergizes with TMZ to exert potent antitumor activity in the murine multiple metastatic melanoma model and MagIC-PDX model. The MagIC-PDX model accurately reproduced patient-like metastatic dissemination. These findings support further development of MR001 based combination therapies and highlight MagIC-PDX as a rapid, patient-relevant platform for preclinical testing and precision modeling.

Acute myeloid leukemia (AML) remains a therapeutic challenge due to drug resistance and relapse, which are often driven by the protective bone marrow (BM) niche. Conventional xenograft models fail to adequately recapitulate this niche-specific pathophysiology. To overcome this limitation, a novel magnetically targeted intramedullary (MagIC-TI) xenograft model was developed. Magnetically labeled doxorubicin (DOX)-resistant HL60 cells (Mag-Re) were injected into the femurs of NSG (nonobese diabetic [NOD] Cg-PrkdcscidIL2rgtm1Wjl/SzJ) mice using a patented microinjection syringe under localized magnetic guidance. With the MagIC-TI model, rapid (day 1) and specific (100% by day 7) leukemic engraftment was achieved within the femoral BM, whereas intravenous (IV) injection led to delayed (mean 23.67 ± 10.26 days) and disseminated engraftment. Bioluminescence imaging, histopathological analysis, flow cytometry, and molecular assays confirmed that disease was localized in the MagIC-TI model. In contrast, extramedullary infiltration, predominantly in the lungs, spleen, liver, and kidneys, was observed early in progression in the IV model. The MagIC-TI model discriminated drug responses, showing effective tumor burden reduction with homoharringtonine (HHT) and unequivocal DOX resistance, a distinction that was obscured in heterogeneous IV models. Furthermore, employing a semisolid decalcification (SSD) system preserved green fluorescent protein (GFP) fluorescence, enabling high-resolution visualization of engrafted cells within bone tissue. The MagIC-TI model enables BM-targeted, rapid, and efficient leukemic engraftment and allows discrimination of drug sensitivity and resistance. This model provides a robust and reproducible platform for modeling the leukemia BM niche and for preclinical evaluation of niche-directed therapies.

OBJECTIVES:To evaluate the efficacy of CD4/TGF-β bispecific antibody in a mouse model of peritoneal metastasis of melanoma. METHODS:For drug safety testing, 20 human CD4 transgenic C57BL/6J mice were randomized into 4 groups (n=5) for intravenous injections of PBS or 2.5, 5, or 10 mg/kg CD4/TGF‑β bispecific antibody, and the changes in general condition, body weight and body temperature were observed. Another 20 transgenic C57BL/6J mice were randomized into two groups to receive intraperitoneal injection of magnetized B16F10-GL melanoma cells expressing green fluorescent protein and luciferase with or without application of a magnet (3 mm in diameter) to the right abdominal skin before cell injection. Three days later, each group was further divided into two groups for treatment with PBS or CD4/TGF-β bispecific antibody (300 μg) twice a week. In vivo imaging was performed at different time points to assess fluorescence distribution and intensity. On day 14, the mice were euthanized and tumor burden and dissemination were evaluated by gross observation, histopathological analysis, immunofluorescence staining, and RT-qPCR. RESULTS:Injection of the antibody did not produce any significant adverse effects in the mice. In the tumor-bearing mice, the application of a magnet significantly accelerated tumor development (3.80±1.79 vs 9.20±2.17 days; P=0.003) and resulted in precise and consistent tumor formation in the parietal peritoneum. Magnet application did not significantly affect survival of the mice but significantly prolonged the therapeutic window (4.60±1.95 vs 10.00±1.73 days; P=0.002). The mice treated with CD4/TGF‑β bispecific antibody had significantly reduced tumor burden irrespective of the inoculation approach, and showed dense encapsulation of the tumor foci by type III collagen, whereas minimal type III collagen deposition and abundant tumor cells were observed in PBS-treated mice. Treatment with the antibody significantly downregulated the expression of melanoma-associated gene MITF, and the reduction was more pronounced in the magnet group. CONCLUSIONS:The CD4/TGF‑β bispecific antibody shows significant antitumor efficacy and good safety in the mouse model of peritoneal metastasis of melanoma.

Wearable microneedle patches offer significant promise for biomarker detection and drug delivery, particularly when coupled with electrochemical analysis. However, the reliance of conventional electrochemical detection on external power sources impedes device portability. To address this limitation, we developed a biofuel cell-based self-powered wearable microneedle patch for the non-invasive monitoring of lactic acid in interstitial fluid (ISF). A conductive microneedle array was fabricated by incorporating carbon nanotubes (CNTs) into an epoxy resin matrix. The microneedles were subsequently functionalized with lactic acid oxidase (LOx) at the anode and platinum nanoparticles (PtNPs) at the cathode. This configuration enabled real-time, in situ lactic acid monitoring. During operation, LOx catalyzes the oxidation of lactic acid to pyruvate, generating electrons at the anode, while PtNPs facilitate the reduction of oxygen to water at the cathode. Lactic acid quantification was achieved by measuring the resulting open-circuit potential (OCP) between the anode and cathode using an external potable potentiometer, with OCP data transmitted wirelessly to a smartphone via Bluetooth. The sensor demonstrated a strong linear relationship between OCP and lactic acid concentration across the physiologically relevant range of 0-10 mM, achieving quantitative detection within 2 min. Furthermore, the microneedle patch exhibited excellent mechanical integrity and electrical conductivity and delivered robust detection performance in a mouse model experiment. This work establishes a versatile platform for developing wearable sensors suitable for non-invasive, personalized home health monitoring.

An ideal bone metastasis animal model is critical and fundamental for mechanistic research and following development of new drug and treatment. Caudal artery (CA) injection allows bone metastasis in the hindlimb, while in-depth targeted and quantitative studies of bone metastasis require a new model to overcome its limitations. Here, we developed a targeted, quantitative, and highly consistent method for the modeling of bone metastasis with cell-based magnetic micro-living-motor (MLM) system created by effectively combining Fe3O4PDA-Au with biosafety. The MLM system can achieve efficient migration, target site colonization and control tumorigenesis in bone precisely with the application of a magnetic field. In vivo, day 3 post cell injection, tumor bone metastasis signals were observed locally in the injected femur among 82.76% mice of the MLM group as compared to the 56.82% in the CA group, and the signal intensity was 45.1 and 95.9 times stronger than that in the left and right lower limbs of the CA group, respectively. Post-injection day 28, metastasis in vital organs was reduced by approximately 90% in the MLM group compared to the CA group. Our innovative use of the MLM system in the field of tumor modeling opens a new avenue for exploring the mechanisms of tumor bone metastasis, recurrence and drug resistance.

Background: The chimeric antigen receptor T-cell (CAR-T) and artificial intelligence (AI) derived new drugs have significantly improved the survival rates of hematological malignancies (HM) patients, but many HM are still drug-resistant. More importantly, choosing the best drugs for individual patient with lower side effects remains a huge challenge. The personalized treatment becomes increasingly important, especially for the rapidly growing elderly patient population. Patient-derived xenograft (PDX) models are powerful tools for personalized treatment. However, traditional intravenous PDX models for HM often have low success rates (10%-40%), long establishment time (4-6 months), and do not adequately reflect patient's clinical characteristics. As a result, the traditional PDX remains largely a concept and fails to meet the clinical needs of most patients. Previous studies of us have proved that magnetically induced cells (MagIC) can promote the homing of various cells to the bone marrow, thereby facilitating the rapid reconstruction of the tumor microenvironment and the establishment of PDX (MagIC-PDX) models. Objective: To develop personalized therapy of drug-resistant HM patients, MagIC-PDX is combined with gene marking of malignant cells, creating an innovative and rapid technology for screening antitumor drugs. Methods: 1.1 Model Establishment: On day 0, mononuclear cells, including primary malignant cells and microenvironment-supporting cells, were isolated from the bone marrow of drug-resistant patients, then labeled overnight with recombinant lentiviral vectors carrying luciferase and GFP. On day 1, the cells were magnetized at 37 degree Celsius for 30min by the “magnetic nanomotors”, then the magnetized cells were injected into the right femur of NCG mice guided by a precise overnight magnetic field (MagIC-PDX group), a conventional IV-PDX (IV-PDX group) was established as a control by tail vein injection. 1.2 Conventional Drug Testing: Once the stable tumor signals were detected in MagIC-PDX group (within 1 week) , clinical chemotherapy drugs such as doxorubicin, cytarabine, bortezomib, and dexamethasone were tested. Further assessment of their efficacy in killing tumor cells are done by bioluminescence imaging, flow cytometry, and pathological techniques. IV-PDX group was used as control. 1.3 Second Round of AI Assistant Drug Screening: If the PDXs showed drug resistant to the 1stround drug screening, a 2nd round of drug screening will be performed based on the MICM information of the patient and AI pre-selected potential drugs. Bone marrow cells of multi-round-drugs' resistant mice were frozen in cell banks for further mechanism studies. Results: 2.1 Model Establishment: Most mice in MagIC-PDX group obtained stable and precise bioluminescent signals at the injection site on day 4, (95.3±6.5)% (n=5), and the signals expanded over time. All untreated mice in MagIC-PDX group developed HM significant clinical characters in the end. In comparison, the traditional IV-PDX group mice requires at least 3 weeks until the detection of unevenly distributed signals, and has a much shorter lifespan (28.4±2.7 vs 62.4±4.8)d, leading to a much smaller experimental window (14.4±2.7 vs 59.4±4.8)d than MagIC-PDX group. 2.2 Conventional Drug Testing and Second Round of Drug Screening: Based on the immediately diminished tumor load signals of myeloma in the MagIC group, bortezomib and dexamethasone treatment are chosen. However, those treated mice relapsed in 3 weeks, showing a developed resistance to the above mentioned treatments. Therefore, we implemented the second round of AI-designed CD4/TGF-β bi-specific antibody treatment, which showed good effect on inhibiting the development of bortezomib/dexamethasone-resistant myeloma. Conclusion: MagIC-PDX is a powerful new kind of PDX model, which allows fast drug screening and mechanism study. This research presents a pivotal tool for advancing personalized treatment.

Background: Organoids are crucial for tumor mechanism study and new drug development. Studies showed that Patient-derived xenograft (PDX) models are helpful for the subsequent construction of organoids. However, the fabrication of either PDXs and organoids remain challenging for hematological malignancies (HM). Traditional PDX fabrication through tail vein injection (IV-PDX) succeeds with probability 10%-40%, and needs 4-6 months. In order to solve this problem, we developed a new model of PDX, helping magnetically-induced-cells (MagIC) home to bone marrow (BM), which is named as MagIC-PDX. It shows clinical features of HM and only needs weeks to fabricate, after which we can easily harvest BM with expanded malignant cells. Objective: To explore the best experimental elements combination for constructing organoids of HM with the BM of MagIC-PDX Strategy. Methods: 1.1 Primary BM isolation and magnetization: Isolate the BM from drug-resistant HM (acute leukemia or multiple myeloma etc.), mononuclear cells were separated by Ficoll and labelled overnight with recombinant lentiviral vectors carrying luciferase and GFP, then the cells were non-specifically magnetized with the “magnetic nanomotors”for 30mins, at 37 ℃. 1.2 PDX modeling: the magnetized cells were inoculatedinto the right femur of 6-8 w NSG female mice by our patented needle (CN205460216U) under a precise magnetic field overnight to help the target homing of malignant cells to BM. The survival, peripheral blood count and weight of mice were monitored, and tumor load and metastasis were studied with bioluminescence at least once a week. BM puncture were performed weekly with the same patented needle, then studied by BM smears, flow cytometry, FISH and qPCR (MICM), the MICM information, and compared with the clinical data. 1.3 T-Trap treatment: CD4/TGF-βbi-specific antibody (T-Trap, Majory, China) were applied 300 µg p. to the mice 2 weeks before the BM harvesting, untreated mice were set as control group. 1.4 Organoids Construction: Extract BM on d28 and culture the cells with “magnetic nanorobots” for 30mins at 37℃, then the magnetized BM were cultured in the AMO Organoids culture system for the organoids with or without precise maegnetic fields, and the number of oganoids per million cells with a diameter more than 2.5mm (d>2.5mm) on d4 were recorded. 1.5 Grouping and data statasis: Four groups of experiments were compared, includes T-Trap, MagIC, T-Trap+MagIC and negative control group. Results: 2.1 The magnetization rate of BM cells are (87.8±8.1)%, n=5. The MagIC-PDX model can be fabricated within one week, with success rates (95.3±6.5)%, n=5, showing consistent and stable bioluminescent signals at the injection site, which expanded over time. The traditional IV-PDX requires at least 3 weeks until the detection of unevenly distributed signals, and has a much shorter lifespan (28.4±2.7 vs 62.4±4.8)d, leading to a much smaller experimental window (14.4±2.7 vs 59.4±4.8)d than MagIC-PDX group. 2.2 Organoids formation: The combination of T-Trap+MagIC in the AMO Organoids culture system performed the best: Every million cells, the number of d>2.5mm organoids on d4 among the four different groups (T-Trap+MagIC, MagIC, T-Trap, and negative control group (n=5)) are 22.6±16.4, 6.0±1.6, 2.0±1.9 and 0±0 respectively. The T-Trap+MagIC and MagIC group had significantly better results than pure T-Trap or negative groups (p<0.01). Discussion: The acceleration of PDX modeling and organoid construction from HM by T-Trap+MagIC technology could be attributed to the following mechanisms: a) The non-specific homing of HM cells in mouse bone marrow, b) rapid expansion of malignant cells facilitating organoid construction, and c) the increase of local collagen in BM by T-Trap, and the magnetic force integrating the cells by MagIC. Conclusion: MagIC-PDX Model combined with T-Trap is a new organoid-forming method of drug-resistant HM, which will facilitate the future new drugs' development, mechanisms study, and personalized medicine for malignancies.

Chronic graft-versus-host disease (cGVHD) involves multiple organs, but little is known about bone marrow (BM) alterations caused by cGVHD. In mice and humans, we found that cGVHD is associated with BM fibrosis resulting in T cell infiltration, IgG deposition, and hematopoietic dysfunction. Macrophages and Nestin+ mesenchymal stromal cells (MSCs) participated in the process of BM fibrosis during BM cGVHD development. BM macrophage numbers were significantly increased in mice and humans with BM fibrosis associated with cGVHD. Amplified macrophages produced TGF-β1, which recruited Nestin+ MSCs forming clusters, and Nestin+ MSCs later differentiated into fibroblasts, a process mediated by increased TGF-β/Smad signaling. TLR4/MyD88-mediated activation of endoplasmic reticulum (ER) stress in macrophages is associated with fibrosis by increasing Nestin+ MSC migration and differentiation into fibroblasts. Depletion of macrophages by clodronate-containing liposomes and inhibition of ER stress by 4-phenylbutyric acid reversed BM fibrosis by inhibiting fibroblast differentiation. These studies provide insights into the pathogenesis of BM fibrosis during cGVHD development.

Background aims: Bone marrow-derived hematopoietic stem cell transplantation/hematopoietic progenitor cell transplantation (HSCT/HPCT) is widely used and one of the most useful treatments in clinical practice. However, the homing rate of hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs) by rou-tine cell transfusion is quite low, influencing hematopoietic reconstitution after HSCT/HPCT.Methods: The authors developed a micro-living motor (MLM) strategy to increase the number of magnetically empowered bone marrow cells (ME-BMCs) homing to the bone marrow of recipient mice.Results: In the in vitro study, migration and retention of ME-BMCs were greatly improved in comparison with non-magnetized bone marrow cells, and the biological characteristics of ME-BMCs were well maintained. Differentially expressed gene analysis indicated that ME-BMCs might function through gene regulation. In the in vivo study, faster hematopoietic reconstitution was observed in ME-BMC mice, which demonstrated a better survival rate and milder symptoms of acute graft-versus-host disease after transplantation of alloge-neic ME-BMCs.Conclusions: This study demonstrated that ME-BMCs serving as MLMs facilitated the homing of HSCs/HPCs and eventually contributed to earlier hematopoietic reconstitution in recipients. These data might provide useful information for other kinds of cell therapies.(c) 2022 Published by Elsevier Inc. on behalf of International Society for Cell & Gene Therapy.

Overexpression of Wilms’ tumor (WT1) is frequently observed in myelodysplastic syndrome (MDS), which has been proposed as a prognostic marker. However, the prognostic role of WT1 expression in different contexts remains to be fully elucidated. We retrospectively assessed the relationships between WT1 levels and preexisting prognostic factors to further investigate its prognostic role under different contexts. In our study, WT1 expression was positively correlated with WHO 2016 classification and IPSS-R stratification. Lower WT1 expression was found in relation to TET2, TP53, CD101, or SRSF2 mutations, while mutant NPM1 patients possessed higher level. Notably, WT1 overexpression maintained its inferior prognostic effect on overall survival (OS) in TP53-wild patients but not in TP53-mutated group. In multivariate analysis, higher WT1 expression was a risk factors for OS in EB patients without TP53 mutations. Overall, WT1 expression was useful to predict prognosis for MDS and its prognostic role was impacted by some gene mutations.

The rapid and specific point-of-care (POC) analysis of virulent pathogenic strains plays a key role in ensuring food quality and safety. In this work, a paper-based fluorescent phage biosensor was developed for the detection of the virulent E. coli O157:H7 strain (as the mode of virulent pathogens) in food samples. Firstly, phages that can specifically combine with E. coli O157:H7 (E. coli) were stained with SYTO-13 dye to prepare a novel fluorescent probe (phage@SYTO). Simultaneously, a micro-porous membrane filter with a pore size of 0.45 μm was employed as a paper chip so as to retain the E. coli-phage@SYTO complex (>1.2 μm) on its surface. The phage@SYTO (200 nm in size) was able to pass through the pores of the chip, and the complex could be retained on the paper chip using the free phage@SYTO probes. The E. coli-phage@SYTO could emit a visual fluorescent signal (excited at 365 nm; emitted at 520 nm) onto the chip, which could be detected by a smartphone to reflect the concentration of E. coli. Under optimized conditions, the detection limit was as low as 50 CFU/mL (S/N = 3) and exhibited a wide linear range from 102 to 106 CFU/mL. The sensor has potential application value for the quick and specific POCT detection of virulent E. coli in foods.

Rapid and specific detection of virulent bacterial strains is a great challenge for food safety regarding large amounts of contaminated samples. Herein, a dual-mode hydrogel array biosensor was constructed to simultaneously rapidly screen and precisely quantitatively detect virulent Escherichia coli O157:H7 (E. coli O157:H7) based on a novel DNA-modified phage probe. First, E. coli O157:H7 was incubated with alginate to form the E. coli O157:H7/hydrogel premix complex. Subsequently, hydrogel formation by cross-linking upon the addition of calcium ions and phages for E. coli O157:H7 modified with a DNA primer (phage-DNA) was added to the alginate hydrogel. The DNA on the complex could trigger rolling circle amplification (RCA) to form a phage probe containing a long-chain DNA skeleton (phage@RCA-DNA). The RCA-DNA was then hybridized with the complementary DNA (cDNA) to form double-stranded DNA fragments (phage@RCA-dsDNA), which could be stained by the SYBR Green dye to emit visual green fluorescence (FL) and determined by a smartphone for rapid screening. Meanwhile, the unreacted cDNA in the supernatant could be quantitatively detected by microfluidic chip electrophoresis (MCE). The signal decrement was also proportional to the bacterial concentration. The detection limit values of E. coli O157:H7 were 50 CFU mL-1 by the FL signal and 6 CFU mL-1 by the MCE signal. The two results could be mutually corrected to decrease the false-positive results. This assay was also employed to detect virulent Salmonella Typhimurium (S. Typhimurium) using the corresponding S. Typhimurium phage@RCA-DNA probe. All these results demonstrated that the universal bioassay was suitable for simultaneous rapid screening and precisely quantitative detection of virulent bacterial strains.

OBJECTIVE:To investigate the effect of thrombospondin-1 (TSP-1) on apoptosis of human megakaryocytic leukemia cell line Meg-01 and its possible mechanism.METHODS:The expression of CD36 antigen in Meg-01 cells was detected by flow cytometry and immunocytochemistry. Meg-01 cells were cultured for 48 hours with TSP-1 and CD36 antibody FA6-152 at different concentrations. The early apoptosis and activity of caspase-3 were detected by flow cytometry. The effect of TSP-1 on the growth and differentiation of megakaryocytes was investigated by cell counting and CFU-MK culture.RESULTS:The flow cytometry and immunocytochemistry showed that CD36 antigen was expressed on the surface of Meg-01 cells. TSP-1 (5 μg/ml) inhibited the growth of Meg-01 cells, but had unobvious effect on M-07e cells. After addition of CD36 antibody FA6-152 (5, 10, and 25 μg/ml), the inhibition effect of TSP-1 was significantly reduced. TSP-1 (2.5, 5, and 7.5 μg/ml) increased the positive expression of Annexin V (P<0.01) and caspase-3 activity (P<0.01), which indicated that TSP-1 had a significant effect on inducing apoptosis. After addition of CD36 antibody FA6-152 (25 μg/ml), the apoptosis induced by TSP-1 in Meg-01 cells was significantly reduced. TSP-1 (5, 10, and 25 μg/ml) could significantly inhibit the formation of CFU-MK in mouse bone marrow cells, while β-TG could not. CD36 antibody FA6-152 (25 μg/ml) could significantly reduce the inhibition of TSP-1 on CFU-MK.CONCLUSION:TSP-1 may induce apoptosis of megakaryocytic leukemia cell line Meg-01 cells via CD36/caspase-3, which provides a potential new drug development and treatment target for clinical treatment of megakaryocytic leukemia.

Background: Thrombospondin 1 (TSP-1) is an extracellular matrix protein that interacts with a wide array of ligands including cell receptors, growth factors, cytokines, and proteases to regulate various physiological and pathological processes. TSP-1 induces apoptosis of endothelial and cancer cells via its receptor CD36. This study was to investigate the effect of TSP-1 on apoptosis of human megakaryocytic leukemia cell line Meg-01 and its possible mechanism.

Abstract Background Early hematopoietic reconstitution is essential for improving survival and reducing complications after hematopoietic stem/progenitor cell (HSC/HPC) transplantation (HSCT/HPCT). Increasing HSC/HPC homing to the bone marrow is a potential approach for promoting hematopoietic reconstitution. Methods We proposed the transplantation of HSCs/HPCs with a magnetism-induced cell-targeting transplantation (MagIC-TT) strategy. HSCs/HPCs were magnetized with CD45 microbeads. The biological characteristics (morphology, proliferation, viability, and ferroptosis) and target migration ability of these cells were studied in vitro. The hematopoietic reconstitution experiments were constructed in vivo in autologous and allogeneic bone marrow transplantation models with grouping showed as Table 1. The therapeutic effects were assessed by survival, donor chimerism, routine blood examination and histological analysis. We also performed transcriptomic sequencing for further mechanistic studies. Results The biological characteristics was found no significant difference between the MagIC-TT and non-MagIC-TT groups, while migration ability was greatly improved with MagIC-TT (Data not showed). The survival rate was higher in the MagIC-TT group and significantly different in the allogeneic model (P<0.05). Hematopoietic reconstitution of donor chimerism, WBCs, HGB, and PLTs was faster in the MagIC-TT groups (within 22 days) (Figure 1). Confocal observation showed that more donor cells (eGFP +) were retained in the injected femur of the MagIC-TT group than in the femur of the non-MagIC-TT group 7 days after transplantation (P<0.05) (Figure 2). The severity of aGVHD (Assessed by survival, body weight, back arching, fur losting, diarrhea etc.) was reduced in the MagIC-TT groups in the allogeneic model (P<0.05) (Data not showed). Transcriptome sequencing revealed differentially expressed genes (DEGs) involved in localization/locomotion and pathways, cytokine-cytokine receptor interactions and chemokine signaling pathways between the two groups (Figure 3). Conclusion The MagIC-TT strategy improves HSC/HPC homing, resulting in faster hematopoietic reconstitution in a murine bone marrow transplantation model. Key words Magnetism; Hematopoietic Stem Cell Transplantation (HSCT); Cell Homing; Hematopoietic Reconstitution; Ferroptosis Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

目的 医疗机构人员密度高,有必要建立监测和控制多种蚊媒传染病传播的方案.方法 在广州市某三甲医院部分建筑内以诱蚊灯法监测成蚊种类和密度,提取成蚊核酸,以多重定量PCR检测登革热、乙型脑炎等多种DNA和RNA病毒,根据检测结果以常规措施或额外措施灭蚊.结果 2019年5-11月医院共收治162例登革热患者,未发生院内感染.在30个蚊虫监测点共捕获成蚊14批次共4881只,其中库蚊3341只(68.45％),伊蚊725只(14.85％)及其他815只(16.70％).发现特定区域成蚊体内Ⅰ型登革热病毒和单纯疱疹病毒各1次阳性,采取额外灭蚊措施,无人员出现感染.结论 通过定期捕蚊和定量PCR检测成蚊体内多种蚊媒病毒,可调整灭蚊措施,防控院内蚊媒传染病的发生.

OBJECTIVE:To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS).METHODS:97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed.RESULTS:MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685).CONCLUSION:Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.

OBJECTIVE To investigate the correlation between U2AF1 gene mutation and clinical manifestations and prognosis in patients with myelodysplastic syndromes (MDS). METHODS The clinical data of 203 MDS patients who accepted Next Generation Sequencing (NGS) was retrospectively analyzed in Nanfang Hospital, Southern Medical University from December 2012 to October 2019. According to whether the patients had U2AF1 gene mutation, the patients were divided into U2AF1 mutated group and non-mutated group, and the relationship between gene mutation characteristics and clinical manifestations and prognosis was analyzed. Then according to the difference of the mutation site of U2AF1, the patients in U2AF1 mutated group were divided into U2AF1S34 mutated group and U2AF1Q157/R156 mutated group, and the correlation between gene mutation characteristics and prognosis was analyzed. RESULTS The incidence of U2AF1 mutation in MDS patients was approximately 11.3% (23/203), and the mutation frequency of U2AF1 allele was 32.5%. The male ratio in U2AF1 mutated group was significantly higher than that in U2AF1 non-mutated group (P=0.001). There was no patient who had complex karyotypes or TP53 gene mutation in U2AF1 mutated group. There were no significant differences in ages, blood parameters, bone marrow blasts, WHO 2016 classification, IPSS-R category, chromosomal abnormalities like del(5q), -7/del(7q), del(20q), +8, and gene mutation like ASXL1, DNMT3A, RUNX1, SF3B1, and SRSF2 mutation between U2AF1 mutated group and the non-mutated group. Compared with the non-mutated group, there was no significant difference in the overall survival time (P=0.377), the time of acute myeloid leukemia (AML) transformation (P=0.681), and the response rate to hypome- thylating agents in U2AF1 mutated group (P=0.556). Besides, no differences were observed in sex, diagnosis age, WHO 2016 classification, IPSS-R category, blood parameters, overall survival time, and AML transformation time between U2AF1S34 mutated group and U2AF1Q157/R156 mutated group. CONCLUSION The U2AF1 gene mutation dose not affect the survival time, AML transformation time, and response rate to hypomethylating agents in MDS patients. Besides, there are no statistical differences in the clinical characteristics and prognosis of MDS patients between U2AF1S34 mutated group and U2AF1Q157/R156 mutated group. Transplantation shows no significant benefit for patients with U2AF1 mutation.