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In recent years, there has been an increasing lack of social responsibility, such as low credibility of information disclosure, product quality defects, food safety, and other issues. This has had a certain impact on supply chain performance and has become an important topic of sustainable supply chain research. This study considers the relationship between logistics corporate social responsibility and supply chain performance. Structural equation models were built to explore the relationship between logistics corporate social responsibility, supply chain collaboration, and supply chain performance, and the bootstrap method was used to build path models to explore whether there is a mediation effect between logistics corporate social responsibility and supply chain performance. The results show that logistics corporate social responsibility has a significant positive impact on supply chain coordination, and logistics corporate social responsibility and supply chain coordination also have a significant positive impact on supply chain performance. Supply chain coordination plays an intermediary role between logistics corporate social responsibility and supply chain performance. Based on these results, it is suggested that logistics enterprises improve their awareness of fulfilling corporate social responsibility, improve transparency, strengthen supply chain collaboration, and accept the role of supervision and management at the government level.

Cuproptosis is an unusual form of cell death caused by copper accumulation in mitochondria. Cuproptosis is associated with hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) have been shown to be effective prognostic biomarkers, yet the link between lncRNAs and cuproptosis remains unclear. We aimed to build a prognostic model of lncRNA risk and explore potential biomarkers of cuproptosis in HCC. Pearson correlations were used to derive lncRNAs co-expressed in cuproptosis. The model was constructed using Cox, Lasso, and multivariate Cox regressions. Kaplan–Meier survival analysis, principal components analysis, receiver operating characteristic curve, and nomogram analyses were carried out for validation. Seven lncRNAs were identified as prognostic factors. A risk model was an independent prognostic predictor. Among these seven lncRNAs, prostate cancer associated transcript 6 (PCAT6) is highly expressed in different types of cancer, activating Wnt, PI3K/Akt/mTOR, and other pathways; therefore, we performed further functional validation of PCAT6 in HCC. Reverse transcription–polymerase chain reaction results showed that PCAT6 was aberrantly highly expressed in HCC cell lines (HepG2 and Hep3B) compared to LO2 (normal hepatocytes). When its expression was knocked down, cells proliferated and migrated less. PCAT6 might be a potential biomarker for predicting prognosis in HCC.

The TiO2/Mn0.2Cd0.8S hollow heterojunction with Mn/Cd bimetallic synergy is prepared via a continuous chemical-hydrothermal-etching method. There, the TiO2 shell and Mn0.2Cd0.8S nanoparticles were deposited by continuous chemical-hydrothermal method on the surface of SiO2 template, and subsequently the SiO2 template was etched via a chemical method. Evaluated by HER, the as-prepared TiO2/Mn0.2Cd0.8S hollow heterojunction exhibits an obvious photocatalytic enhancement to about ~5822.94 μmol/g∙h(~40 folds of TiO2, ~7 folds of Mn0.2Cd0.8S), which can be mainly ascribed to that, the narrow band gap of Mn0.2Cd0.8S can increase the visible light energy utilization, the TiO2/Mn0.2Cd0.8S heterojunction and Mn/Cd bimetallic synergy can separate/transfer the photo-generated charge carriers efficiently, and the sufficient specific surface areas and actives from 3D hollow structure can promote the charge carrier diffusing into water quickly for achieving H2 generation. Additionally, the hollow 3D structure can provide a decent physical-chemical stability to improve the photocatalytic stability.

A CoxP QDs-MoS2 nanosheets@Ni3S2 nanoarrays/NF with electrocatalytic overall water splitting is fabricated via a simple hydrothermal-electrodeposition method. There, the MoS2@Ni3S2/NF is prepared by a hydrothermal method on the surface of NF, and subsequently the CoxP QDs are deposited by an electrodeposition method on the surface of MoS2 nanosheets. As demonstrated, the as-prepared CoxP QDs-MoS2@Ni3S2/NF presents low overpotentials of 54 mV(HER) at 10 mA cm−2 and 207 mV(OER) at 100 mA cm−2 in 1.0 M KOH, and exhibits a decent overall water splitting performance, including the overpotential of 1.39 V(vs RHE) at 10 mA cm−2, which can be mainly ascribed to the hierarchical nanostructure can increase MoS2 nanosheets and CoxP QDs efficiently for increasing the HER/OER active sites. Additionally, the extra HER active sites of edge S atoms from MoS2 nanosheets, the extra OER active sites induce by the presence of Ni3+/Ni2+ and Co3+/Co2+ mixed state, and low overpotential of Ni3S2, MoS2 and CoxP QDs are also important reasons.

Acute promyelocytic leukemia (APL) patients with progressive leukocytosis are more likely to have various complications and poor outcomes. However, the regulatory roles of microRNAs in the leukocytosis of APL have not been clarified. Our study aims to evaluate the effects of miRNAs on leukocytosis during induction therapy of APL patients and explore its potential mechanisms. During induction treatment, patients with white blood cell count higher than 10 × 109/L were divided into leukocytosis group and others were nonleukocytosis group. Using microarray assays, we found that miR-139-5p was significantly downregulated in the leukocytosis group. Elevated expression of miR-139-5p inhibited the proliferation of NB4 cells by arresting the cell cycle and inducing apoptosis. We further identified that MNT was a target of miR-139-5p. miR-139-5p significantly inhibited the proliferation, invasion, and migration function of NB4 cells through targeting MNT. Strategies for regulating miR-139-5p or MNT expression might provide new therapeutic approaches for progressive leukocytosis in APL.

This study aimed to evaluate treatment response, survival, safety profiles, and predictive factors to chimeric antigen receptor T cell (CAR-T) therapy in Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL). 39R/R B-ALL patients who underwent CAR-T therapy were included. Baseline data were collected from patients’ electronic medical records. Patients’ peripheral bloods, bone marrow aspirates, and biopsies were obtained for routine examination, and treatment response and survival profiles as well as adverse events were evaluated. The rates of complete remission (CR), CR with minimal residual disease (MRD) negative/positive, and bridging to hematopoietic stem-cell transplantation (HSCT) were 92.3%, 76.9%, 15.4%, and 43.6%, respectively. The median event-free survival (EFS) was 11.6 months (95% confidence interval (CI): 4.0–19.2 months) and median overall survival (OS) was 14.0 months (95% CI: 10.9–17.1 months). Bridging to HSCT independently predicted better EFS and OS, while high bone marrow blasts level independently predicted worse EFS. The incidence of cytokine release syndrome (CRS) was 97.4%, and refractory disease as well as decreased white blood cell independently predicted higher risk of severe CRS. Other common adverse events included hematologic toxicities (grade I: 5.1%, grade II: 7.7%, grade III: 17.9%, grade IV: 69.2%), neurotoxicity (28.2%), infection (38.5%), and admission for intensive care unit (10.3%). In conclusion, CAR-T therapy presents with promising treatment response, survival and safety profiles, and higher disease burden predicts worse survival as well as increased risk of severe CRS in Chinese R/R B-ALL patients.

In recent years, how to further enhance the efficiency of photocatalytic hydrogen generation has become a research hotspot. At present, the metal-organic-frameworks (MOF) has attracted much attention in the field of catalysis due to its special physical and chemical properties. Herein, the hollow core-shell Co3O4/TiO2 heterojunction is prepared by deposition and annealing method with ZIF-67 as self-sacrificial templates and metal precurous. The characterzation of XRD, SEM, and TEM indicate that the hollow core-shell Co3O4/TiO2 heterojunction is synthesized successfully. The characterzation of UV, PL indicate that the Co3O4/TiO2 show superior photoelectric performance. By evaluation, the Co3O4/TiO2 heterogeneous catalyst exhibits a remarkable photocatalytic hydrogen production performance, which is ∼11 and ∼14 times higher than that of pure Co3O4 and TiO2. Studies prove that the formation of heterojunction can promote charge carriers separation, the hollow structure can raise the solar efficiency, offer more surface areas and active sites, all these are beneficial for photocatalytic performance.

Limin Li,* Xiaoqian Zhang,* Hongjuan Yu, Mingwen Zhang, Mengyuan Xu, Jie Liu, Yueyue Fu, Hongbin Meng, Chengfang Lyu, Xiaoxia Li, Jin Zhou Department of Hematology, Institute of Hematology and Oncology of Heilongjiang Province, Hematology and Oncology Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Background: Relapsed and refractory acute myeloid leukemia (RR-AML) still poses major treatment concerns. Current treatments include high doses of cytarabine or fludarabine in combination with cytarabine and G-CSF (FLAG), but provide mixed results. Low-dose decitabine, a hypomethylating drug, in combination with aclarubicin and cytarabine (DAC) has shown safety and efficacy in the treatment of AML; however, clinical data are limited for the treatment of RR-AML.Methods: In this study, we retrospectively compared the response and safety of DAC vs FLAG for RR-AML patients.Results: For the 35 patients with RR-AML enrolled in this study, the overall response rates reached 100% and 55.6% in the DAC group and FLAG group, respectively (P=0.002). Complete response rates after DAC and FLAG treatment were 64.7% and 33.3%, respectively (P=0.002). Median overall survival (95% CI) of the DAC treatment group was significantly higher than for the FLAG group (median not achieved vs 16.8 months, P=0.021).Conclusion: DAC treatment was also more effective in those patients with poor prognosis, suggesting that DAC resulted in a better outcome for RR-AML treatment. In conclusion, in our study, DAC therapy provided more safety and effectiveness and lower toxicity in the treatment of RR-AML compared to FLAG therapy. Keywords: AML, refractory diseases, relapsed diseases, decitabine, chemotherapy

Background/Aims: Pulmonary arterial endothelial plexiform lesions are a basic pathological change associated with pulmonary vascular remodeling and are characterized by the formation of tumorlets as a result of over-growth of endothelial cells. Accumulating evidence suggests that platelet-derived growth factor (PDGF) participates in regulating the progression of pulmonary arterial hypertension. However, whether PDGF promotes the survival of pulmonary arterial endothelial cells (PAECs), as well as the specific molecular mechanisms that underlie its actions, remains unknown. Methods: MTT assays, caspase-3 and caspase-9 activity assays and western blot analysis were performed. Results: We found that both the mRNA and protein expression of PDGF-B was induced by hypoxia and that the inhibitory effects exerted by hypoxia on apoptosis were attenuated by inhibitors of PDGF beta. Moreover, PDGF-B inhibited apoptosis in a dose-dependent manner by stimulating the phosphorylation of both Akt and Stat3, and the PI3K/AKT pathway serves as an up-stream participant in the Stat3 activation stimulated by PDGF-B. Additionally, the anti-apoptotic effects of PDGF-B were abolished when PAECs were treated with either an inhibitor or small interfering RNA targeting Stat3. Conclusions: These observations suggest that PDGF-B is induced by hypoxia and protects against apoptosis via the PI3K/Akt/Stat3 signaling pathway.

Background Coagulopathy is a major cause of early death when arsenic trioxide (As2O3) therapy fails. In addition to the procoagulant properties of blast cells, the cytotoxic therapy may contribute to the coagulation disorders. The aim of the present study was to evaluate the possible impact of As2O3 on membrane alterations, including phosphatidylserine (PS) exposure and microparticle generation, and the consequent procoagulant properties of endothelial cells. Methods Procoagulant activity (PCA) of human umbilical vein endothelial cells (HUVECs) was assessed by measuring clotting time and through purified coagulation complex assays. PS exposure on HUVEC membrane was observed by confocal microscopy and quantified with flow cytometry. In addition, counts and PCA of endothelial microparticles were determined by flow cytometry and plasma coagulation assay. Results As2O3 increased the ability of HUVECs to accelerate coagulation process and promote formation of coagulation complexes. Procoagulant activity corresponded to PS exposed on HUVECs. In coincidence with the PS externalization, As2O3 increased the production of PS-bearing microparticles, which then accelerated fibrin strand formation significantly. By blocking PS, lactadherin was able to inhibit over 90% of the intrinsic tenase/prothrombinase activity of As2O3-treated HUVECs, and restored coagulation times of As2O3–treated cells and microparticles to control levels. Conclusions As2O3 increases PCA of HUVECs through PS exposure and PS-bearing microparticle generation, which might cause thrombosis and act as a contributing factor in As2O3 therapy-related coagulopathy.

Abstract 5185 Administration of various chemotherapeutic agents is associated with an increased risk of thrombotic events. Although vascular endothelium plays a predominant role in blood coagulation and fibrinolysis, the effect of cytotoxic drugs on the procoagulant activity (PCA) of endothelial cells has not been well evaluated. Our study aims to investigate the possibility that daunorubicin, a chemotherapeutic agent, exerts prothrombotic effect on endothelial cells. We tested the impact of daunorubicin on phosphatidylserine (PS) exposure, endothelial microparticles (EMPs) release and consequent PCA. Human umbilical vein endothelial cells (HUVECs) were treated with daunorubicin (0.1, 0.2, 0.5, 1, 2 μ M) for 24 h. PCA of HUVECs was measured using clotting time and purified coagulation complex assays. Counts and PCA of EMPs were evaluated by flow cytometry and clotting time assay, respectively. Lactadherin was used as a novel probe for detection of PS exposure and EMPs release. We found that daunorubicin dose-dependently increased the PS exposure and consequent PCA of HUVECs. Moreover, daunorubicin treatment also enhanced the release of EMPs which were highly procoagulant. This increment was especially significant at 0.2 μ M of daunorubicin or over. Blockade of PS with lactadherin inhibited over 90% of HUVECs and EMPs PCA. However, anti-TF antibody had no significant inhibition effect. Our results demonstrate that daunorubicin treatment enhanced PCA of HUVECs through PS exposure and shedding of procoagulant EMPs. Lactadherin acts as an efficient anticoagulant in this process. Disclosures: No relevant conflicts of interest to declare.

Previous studies have highlighted that the transforming growth factor‑β1 (TGF‑β1) pathway may be activated by hypoxic conditions. TGF‑β1 also participates in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. Furthermore, TGF‑β1 has been reported to participate in the regulation of the progression of pulmonary arterial hypertension (PAH). However, the effect of TGF‑β1 on pulmonary arterial smooth muscle cells (PASMCs) and the corresponding molecular mechanisms remain unclear. The present study aimed to determine whether TGF‑β1 protects against cell apoptosis in PASMCs, and identify the underlying molecular mechanisms. Western blotting, MTT and lactate dehydrogenase activity assays were performed, and the activity of caspase‑3 and caspase‑9 was detected in order to investigate the hypothesis. It was determined that TGF‑β1 may facilitate cell growth in a dose‑dependent manner in serum‑starved PASMCs. Furthermore, it was observed that apoptosis in serum‑starved PASMCs was inhibited by TGF‑β1 via regulation of the expression levels of mitochondrial membrane proteins. Additionally, the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt) pathway was found to be activated by TGF‑β1 in PASMCs, while the inhibition of PI3K/Akt signaling also prevented the apoptosis‑limiting effects of TGF‑β1. These observations suggest that TGF‑β1 protects PASMCs from apoptosis and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway.

Background: Explore the impact of second-generation bisphosphonate drugs pamidronate on proliferation and apoptosis of human multiple myeloma cell line in vitro. Verify the synergistic effect of combination of pamidronate and melphalan on apoptosis of myeloma cells and demonstrate that lactadherin is the most effective probe for apoptosis detection. Method: (1) Myeloma cells were treated with pamidronate or combination of melphalan and pamidronate at different concentrations. The cells were divided into 12 groups and treated with the drugs at intervals of 24 hours for 48 hours. After 48 hours treatment, inhibition rate of cell growth in different group were measured by MTT. (2) Two groups were treated with PBS buffer. PS exposure of the cells treated with drugs was detected using FITC-Annexin-V and FITC-lactadherin by flow cytometry. Result: The increase of the proliferation and effect of apoptosis by pamidronate on multiple myeloma cells was parallel as the increase of pamidronate dose. In combination with melphalan, the effect of apoptosis induction was stronger than single drug group. PS exposure detected by lactadherin was significantly increased as the increase of amidronate concentration. PS exposure in treated group is more than that of control group. Conclusion: Pamidronate exerts effects of growth inhibition and apoptosis induction on multiple myeloma cell in a dose-dependent way; Combination therapy increases apoptosis and exerts a synergistic effect; Lactadherin is the most effective probe in detecting myeloma cell apoptosis.

SummaryThe development of thrombosis in polycythaemia vera (PV) involves multifactorial processes including pathological activation of blood cells. Release of microparticles (MPs) by activated cells in diseases is associated with thrombotic risk, but relatively few data are available in PV. The aim of the present study was to investigate the increase in MP release and exposure of phosphatidylserine (PS) on the outer membrane of MP-origin cells in patients with PV, and to analyse their procoagulant activity (PCA). PS-positive MPs and cells were detected by flow cytometry, while PCA was assessed with clotting time and purified coagulation complex assays. We found that PV patients had elevated circulating lactadherin+ MPs, which mostly originating from erythrocytes, platelets, granulocytes, and endothelial cells, as well as increased PS exposing erythrocytes/platelets as compared to secondary polycythaemia patients or healthy controls. These PS-bearing MPs and cells were highly procoagulant. Moreover, lactadherin competed factor V and VIII to PS and inhibited about 90% of the detected PCA in a dose-response manner while anti-TF antibody did no significant inhibition. Treatment with hydroxyurea is associated with a decrease in PS exposure and lactadherin+ MP release of erythrocytes/platelets. Our data demonstrate that PV patients are characterised by increased circulating procoagulant MPs and PS exposing erythrocytes/platelets, which could contribute to the hypercoagulable state in these patients.

Abstract 3782 Neutrophils, also called polymorphonuclear leukocytes (PMN's) have a half-life of only 6 hours in the blood. Inflammation can further shorten the circulating life-time. A large fraction of the bone marrow capacity is committed to ongoing production of these short-lived cells but the manner of their clearance from the circulation is less well understood. We have previously demonstrated that PMN's are cleared by liver macrophages. However, the details of PMN adhesion-induced PMN clearance in the liver are unknown. The aim of this study is to evaluate a pathway of PMNs clearance by endothelial cells, which are not ordinarily considered phagocytes. Lactadherin is a glycoprotein of milk fat globules and is also secreted by stimulated macrophages. Lactadherin binds phosphatidylserine on apoptotic cells via tandem lectin-homology domains with homology to factor VIII and binds αvβ3 and αvβ5 integrins on phagocytic cells via an RGD sequence in an epithelial growth factor domain. Lactadherin aids in engulfment of senescent lymphocytes by splenic macrophages and mediates an anti-inflammatory response. We utilized lactadherin as a probe to detect phosphatidylserine exposure on aging PMN's and evaluated the lactadherin-dependent engulfment of these PMN's by endothelial cells. Cultured human PMNs from healthy donors, with 95% purity, were 40% and 96% PS-exposure positive at 9 and 24 h, respectively. They displayed a parallel increase in procoagulant supporting, activity related to the PS exposure. Coculture of the aging PMNs and human umbilical vein endothelial cells resulted in phagocytosis of the PMN's, observed by confocal microscopy and electron microscopy. Exogenous lactadherin increased phagocytosis by 3–5 fold during 120 minutes of observation. An anti-lactadherin RGD antibody and an anti-lactadherin C2 domain antibody inhibited phagocytosis to approx 1/2 the background level suggesting that lactadherin secreted by PMN's or neutrophils contributes to the base level of phagocytosis. Clearance of the senescent neutrophils by endothelial cells decreased procoagulant activity >70% and blockade of neutrophil PS with lactadherin reduced procoagulant activity by > 90% indicating the potential role of neutrophil uptake in limiting prothrombotic activity. In a rat model of neutrophil homeostasis we injected low dose lipopolysaccharide (LPS) and gadolinium chloride intravenously to increase the number circulating PMN's and block clearance by Kupffer cells. This allowed observation of PMN adhesion and sequestration in the liver. The number of PMNs peaked at 9 h and decreased to the normal range at 24 h after blockade of Kupffer cells. Blocking the endothelial P-selectin significantly delayed PMN's removal in the liver. Injection of lactadherin promoted the PMNs accumlation and removal. The current results suggest that ECs contribute to maintaining the homeostasis of PMNs in the circulation and a possible role of lactadherin in the EC-mediated clearance. Our results also indicate that lactadherin-mediated clearance may limit procoagulant or prothrombotic activity of senescent PMN's. Disclosures: No relevant conflicts of interest to declare.

Abstract 3150 Poster Board III-87 Background Phosphatidylserine (PS) can support coagulant reactions. However, it is uncertain how the location and extent of PS exposure to the membranes of stored platelets affect such reactions. We compared annexin V with lactadherin as a way of detecting how of PS exposure influences the procoagulant properties of stored platelets in platelet concentrates (PCs). Method PS exposure and the relevant procoagulant activity (PCA) of platelets in 5 different PCs were investigated by flow cytometry, confocal microscopy, coagulation time analysis and enzymatic assays. PS exposure was separately measured using annexin V and lactadherin, respectively. Results Exposure of PS to stored platelets promoted thrombin formation. A progressive increase in PS exposure was detected by flow cytometry. Moreover, using lactadherin, we identifed higher levels of PS exposure on the platelets and platelet-derived microparticles (PMPs) compared to detection using annexin V. The percentage of PS-positive cells was 0.02 % by annexin V versus 0.3 % by lactadherin on day 0, 7.5 % by annexin V versus 12.3 % by lactadherin on day 5, and 29 % by annexin V versus 44.3 % by lactadherin on day 9. Rare microparticles (MPs) were released from fresh platelets, and, the number of PMPs increased approximately 2-fold on day 5 and further progressively increased. Using lactadherin and platelets in the earlier stage of storage, confocal microscopy revealed earlier and localized PS exposure based on plasma membrane staining. For later storage platelets, increased levels of PS-positive platelets and PMPs were clearly detected by both annexin V and lactadherin. Thirty-two nM lactadherin or annexin V prolonged coagulation time 2.4 fold versus 2 fold. The productions of thrombin and intrinsic/extrinsic factor Xase were approximately inhibited 85 % and 60 % by lactadherin and annexin V, respectively. Conclusion PS exposure was localized to the cellular rims, blebbing vesicles and thin elongated filopodia-like areas on banked platelets. Furthermore, lactadherin provides a more accurate measurement of PS exposure and the relevant with PCA, which is an important factor to consider for transfusion medicine. Our findings of elevated PS-positive platelets and PMPs indicate that platelets should not be stored for extended periods of time. Disclosures No relevant conflicts of interest to declare.