Inhibiting Demetalation of Fe─N─C via Mn Sites for Efficient Oxygen Reduction Reaction in Zinc-Air Batteries.

Demetalation caused by the electrochemical dissolution of metallic Fe atoms is a major challenge for the practical application of Fe─N─C catalysts. Herein, an efficient single metallic Mn active site is constructed to improve the strength of the Fe─N bond, inhibiting the demetalation effect of Fe─N─C. Mn acts as an electron donor inducing more delocalized electrons to reduce the oxidation state of Fe by increasing the electron density, thereby enhancing the Fe─N bond and inhibiting the electrochemical dissolution of Fe. The oxygen reduction reaction pathway for the dissociation of Fe─Mn dual sites can overcome the high energy barriers to direct O─O bond dissociation and modulate the electronic states of Fe─N4 sites. The resulting FeMn─N─C exhibits excellent ORR activity with a high half-wave potential of 0.92 V in alkaline electrolytes. FeMn─N─C as a cathode catalyst for Zn-air batteries has a cycle stability of 700 h at 25 °C and a long cycle stability of more than 210 h under extremely cold conditions at -40 °C. These findings contribute to the development of efficient and stable metal-nitrogen-carbon catalysts for various energy devices.

Polarized Ultrathin BN Induced Dynamic Electron Interactions for Enhancing Acidic Oxygen Evolution.

Developing ruthenium-based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect-rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180 mV (at 10 mA cm-2) and long-term operational stability (350 h) are achieved, suggesting potential practical applications. In situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron-rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O-terminal and B-terminal edge establishes electronic back-donation, effectively suppressing the over-oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface.

Electron scale coherent structure as micro accelerator in the Earth's magnetosheath.

Turbulent energy dissipation is a fundamental process in plasma physics that has not been settled. It is generally believed that the turbulent energy is dissipated at electron scales leading to electron energization in magnetized plasmas. Here, we propose a micro accelerator which could transform electrons from isotropic distribution to trapped, and then to stream (Strahl) distribution. From the MMS observations of an electron-scale coherent structure in the dayside magnetosheath, we identify an electron flux enhancement region in this structure collocated with an increase of magnetic field strength, which is also closely associated with a non-zero parallel electric field. We propose a trapping model considering a field-aligned electric potential together with the mirror force. The results are consistent with the observed electron fluxes from ~50 eV to ~200 eV. It further demonstrates that bidirectional electron jets can be formed by the hourglass-like magnetic configuration of the structure.

Lewis Acid Driving Asymmetric Interfacial Electron Distribution to Stabilize Active Species for Efficient Neutral Water Oxidation.

Neutral oxygen evolution reaction (OER) with unique reactive environments exhibits extremely slow reaction kinetics, posing significant challenges in the design of catalysts. Herein, a built-in electric field between the tungstate (Ni-FeWO4 ) with adjustable work function and Lewis acid WO3 is elaborately constructed to regulate asymmetric interfacial electron distribution, which promotes electron accumulation of Fe sites in the tungstate. This decelerates the rapid dissolution of Fe under the OER potentials, thereby retaining the active hydroxyl oxide with the optimized OER reaction pathway. Meanwhile, Lewis acid WO3 enhances hydroxyl adsorption near the electrode surface to improve mass transfer. As expected, the optimized Ni-FeWO4 @WO3 /NF self-supporting electrode achieves a low overpotential of 235 mV at 10 mA cm-2 in neutral media and maintains stable operation for 200 h. Furthermore, the membrane electrode assembly constructed by such self-supporting electrode exhibits robust stability for 250 h during neutral seawater electrolysis. This work deepens the understanding of the reconstruction of OER catalysts in neutral environments and paves the way for development of the energy conversion technologies.

Switching the Oxygen Evolution Mechanism on Atomically Dispersed Ru for Enhanced Acidic Reaction Kinetics.

Designing stable single-atom electrocatalysts with lower energy barriers is urgent for the acidic oxygen evolution reaction. In particular, the atomic catalysts are highly dependent on the kinetically sluggish acid-base mechanism, limiting the reaction paths of intermediates. Herein, we successfully manipulate the steric localization of Ru single atoms at the Co3O4 surface to improve acidic oxygen evolution by precise control of the anchor sites. The delicate structure design can switch the reaction mechanism from the lattice oxygen mechanism (LOM) to the optimized adsorbate evolution mechanism (AEM). In particular, Ru atoms embedded into cation vacancies reveal an optimized mechanism that activates the proton donor-acceptor function (PDAM), demonstrating a new single-atom catalytic pathway to circumvent the classic scaling relationship. Steric interactions with intermediates at the anchored Ru-O-Co interface played a primary role in optimizing the intermediates' conformation and reducing the energy barrier. As a comparison, Ru atoms confined to the surface sites exhibit a lattice oxygen mechanism for the oxygen evolution process. As a result, the delicate atom control of the spatial position presents a 100-fold increase in mass activity from 36.96 A gRu(ads)-1 to 4012.11 A gRu(anc)-1 at 1.50 V. These findings offer new insights into the precise control of single-atom catalytic behavior.

Valence Oscillation of Ru Active Sites for Efficient and Robust Acidic Water Oxidation.

The continuous oxidation and leachability of active sites in Ru-based catalysts hinder practical application in proton-exchange membrane water electrolyzers (PEMWE). Herein, robust inter-doped tungsten-ruthenium oxide heterostructures [(Ru-W)Ox ] fabricated by sequential rapid oxidation and metal thermomigration processes are proposed to enhance the activity and stability of acidic oxygen evolution reaction (OER). The introduction of high-valent W species induces the valence oscillation of the Ru sites during OER, facilitating the cyclic transition of the active metal oxidation states and maintaining the continuous operation of the active sites. The preferential oxidation of W species and electronic gain of Ru sites in the inter-doped heterostructure significantly stabilize RuOx on WOx substrates beyond the Pourbaix stability limit of bare RuO2 . Furthermore, the asymmetric Ru-O-W active units are generated around the heterostructure interface to adsorb the oxygen intermediates synergistically, enhancing the intrinsic OER activity. Consequently, the inter-doped (Ru-W)Ox heterostructures not only demonstrate an overpotential of 170 mV at 10 mA cm-2 and excellent stability of 300 h in acidic electrolytes but also exhibit the potential for practical applications, as evidenced by the stable operation at 0.5 A cm-2 for 300 h in PEMWE.

Ultrafast Combustion Synthesis of Robust and Efficient Electrocatalysts for High-Current-Density Water Oxidation.

The scalable production of inexpensive, efficient, and robust catalysts for oxygen evolution reaction (OER) that can deliver high current densities at low potentials is critical for the industrial implementation of water splitting technology. Herein, a series of metal oxides coupled with Fe2O3 are in situ grown on iron foam massively via an ultrafast combustion approach for a few seconds. Benefiting from the three-dimensional nanosheet array framework and the heterojunction structure, the self-supporting electrodes with abundant active centers can regulate mass transport and electronic structure for prompting OER activity at high current density. The optimized Ni(OH)2/Fe2O3 with robust structure can deliver a high current density of 1000 mA cm-2 at the overpotential as low as 271 mV in 1.0 M KOH for up to 1500 h. Theoretical calculation demonstrates that the strong electronic modulation plays a crucial part in the hybrid by optimizing the adsorption energy of the intermediate, thereby enhancing the efficiency of oxygen evolution. This work proposes a method to construct cheap and robust catalysts for practical application in energy conversion and storage.

Rapid complete reconfiguration induced actual active species for industrial hydrogen evolution reaction.

Rational regulation of electrochemical reconfiguration and exploration of activity origin are important foundations for realizing the optimization of electrocatalyst activity, but rather challenging. Herein, we potentially develop a rapid complete reconfiguration strategy for the heterostructures of CoC2O4 coated by MXene nanosheets (CoC2O4@MXene) during the hydrogen evolution reaction (HER) process. The self-assembled CoC2O4@MXene nanotubular structure has high electronic accessibility and abundant electrolyte diffusion channels, which favor the rapid complete reconfiguration. Such rapid reconfiguration creates new actual catalytic active species of Co(OH)2 transformed from CoC2O4, which is coupled with MXene to facilitate charge transfer and decrease the free energy of the Volmer step toward fast HER kinetics. The reconfigured components require low overpotentials of 28 and 216 mV at 10 and 1000 mA cm-2 in alkaline conditions and decent activity and stability in natural seawater. This work gives new insights for understanding the actual active species formation during HER and opens up a new way toward high-performance electrocatalysts.

A stochastic mathematical model of two different infectious epidemic under vertical transmission.

In this study, considering the effect of environment perturbation which is usually embodied by the alteration of contact infection rate, we formulate a stochastic epidemic mathematical model in which two different kinds of infectious diseases that spread simultaneously through both horizontal and vertical transmission are described. To indicate our model is well-posed and of biological significance, we prove the existence and uniqueness of positive solution at the beginning. By constructing suitable Lyapunov functions (which can be used to prove the stability of a certain fixed point in a dynamical system or autonomous differential equation) and applying Itô's formula as well as Chebyshev's inequality, we also establish the sufficient conditions for stochastic ultimate boundedness. Furthermore, when some main parameters and all the stochastically perturbed intensities satisfy a certain relationship, we finally prove the stochastic permanence. Our results show that the perturbed intensities should be no greater than a certain positive number which is up-bounded by some parameters in the system, otherwise, the system will be surely extinct. The reliability of theoretical results are further illustrated by numerical simulations. Finally, in the discussion section, we put forward two important and interesting questions left for further investigation.

Boosting Oxygen Reduction Activity of Manganese Oxide Through Strain Effect Caused By Ion Insertion.

Transition-metal oxides with a strain effect have attracted immense interest as cathode materials for fuel cells. However, owing to the introduction of heterostructures, substrates, or a large number of defects during the synthesis of strain-bearing catalysts, not only is the structure-activity relationship complicated but also their performance is mediocre. In this study, a mode of strain introduction is reported. Transition-metal ions with different electronegativities are intercalated into the cryptomelane-type manganese oxide octahedral molecular sieves (OMS-2) structure with K ions as the template, resulting in the octahedral structural distortion of MnO6 and producing strains of different degrees. Experimental studies reveal that Ni-OMS-2 with a high compressive strain (4.12%) exhibits superior oxygen reduction performance with a half-wave potential (0.825 V vs RHE) greater than those of other reported manganese-based oxides. This result is related to the increase in the covalence of MnO6 octahedral configuration and shifting down of the eg band center caused by the higher compression strain. This research avoids the introduction of new chemical bonds in the main structure, weakens the effect of eg electron filling number, and emphasizes the pure strain effect. This concept can be extended to other transition-metal-oxide catalysts.

Flippases play specific but distinct roles in the development, pathogenicity, and secondary metabolism of Fusarium graminearum.

The membrane trafficking system is important for compartmentalization of the biosynthesis pathway and secretion of deoxynivalenol (DON) mycotoxin (a virulence factor) in Fusarium graminearum. Flippases are transmembrane lipid transporters and mediate a number of essential physiological steps of membrane trafficking, including vesicle budding, charging, and protein diffusion within the membrane. However, the roles of flippases in secondary metabolism remain unknown in filamentous fungi. Herein, we identified five flippases (FgDnfA, FgDnfB, FgDnfC1, FgDnfC2, and FgDnfD) in F. graminearum and established their specific and redundant functions in the development and pathogenicity of this phytopathogenic fungus. Our results demonstrate that FgDnfA is critical for normal vegetative growth while the other flippases are dispensable. FgDnfA and FgDnfD were found crucial for the fungal pathogenesis, and a remarkable reduction in DON production was observed in ΔFgDNFA and ΔFgDNFD. Deletion of the FgDNFB gene increased DON production to about 30 times that produced by the wild type. Further analysis showed that FgDnfA and FgDnfD have positive roles in the regulation of trichothecene (TRI) genes (TRI1, TRI4, TRI5, TRI6, TRI12, and TRI101) expression and toxisome reorganization, while FgDnfB acts as a negative regulator of DON synthesis. In addition, FgDnfB and FgDnfD have redundant functions in the regulation of phosphatidylcholine transport, and double deletion of FgDNFB and FgDNFD showed serious defects in fungal development, DON synthesis, and virulence. Collectively, our findings reveal the distinct and specific functions of flippase family members in F. graminearum and principally demonstrate that FgDnfA, FgDnfD, and FgDnfB have specific spatiotemporal roles during toxisome biogenesis.

Plasmapause surface wave oscillates the magnetosphere and diffuse aurora.

Energy circulation in geospace lies at the heart of space weather research. In the inner magnetosphere, the steep plasmapause boundary separates the cold dense plasmasphere, which corotates with the planet, from the hot ring current/plasma sheet outside. Theoretical studies suggested that plasmapause surface waves related to the sharp inhomogeneity exist and act as a source of geomagnetic pulsations, but direct evidence of the waves and their role in magnetospheric dynamics have not yet been detected. Here, we show direct observations of a plasmapause surface wave and its impacts during a geomagnetic storm using multi-satellite and ground-based measurements. The wave oscillates the plasmapause in the afternoon-dusk sector, triggers sawtooth auroral displays, and drives outward-propagating ultra-low frequency waves. We also show that the surface-wave-driven sawtooth auroras occurred in more than 90% of geomagnetic storms during 2014-2018, indicating that they are a systematic and crucial process in driving space energy dissipation.

Double-Stranded DNA in Exosomes of Malignant Pleural Effusions as a Novel DNA Source for EGFR Mutation Detection in Lung Adenocarcinoma.

Background: Exosomes are cell-derived vesicles and bear a specific set of nucleic acids including DNA (exoDNA). Thus, this study is to explore whether exoDNA in malignant pleural effusions (MPEs) could be a novel DNA source for mutation detection of epidermal growth factor receptor (EGFR). Methods: In this study, 52 lung adenocarcinoma patients were enrolled, and EGFR mutation status was detected with tumor tissues as well as cell blocks and exosomes in MPEs. The sensitivity, specificity and consistency of EGFR detection using exosomes were evaluated, compared with gene detection using tumor tissues and cell blocks. And the clinical response of patients who were detected as EGFR mutation in exosomes and treated with EGFR tyrosine kinase inhibitor (EGFR-TKI) was explored. Results: Gene detection using exosomes showed sensitivity of 100%, specificity of 96.55% and coincidence rate of 98.08% (Kappa = 0.961, P < 0.001), compared with detection using tumor tissues and cell blocks. After EGFR-TKI treatment, patients detected as EGFR mutation by exosomes showed efficacy rate of 83% and disease control rate of 100%. And patients who were detected as wild type in tumor tissues or cell blocks but EGFR mutation in exosomes turned up as PR or SD. Conclusions: These results demonstrated that exoDNA in MPEs could be used as a DNA source for EGFR detection in lung adenocarcinoma.

Molecular dysexpression in gastric cancer revealed by integrated analysis of transcriptome data.

Gastric cancer (GC) is often diagnosed in the advanced stages and is associated with a poor prognosis. Obtaining an in depth understanding of the molecular mechanisms of GC has lagged behind compared with other cancers. This study aimed to identify candidate biomarkers for GC. An integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between GC and normal tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed to identify the functions of the DEGs. Furthermore, a protein-protein interaction (PPI) network of the DEGs was constructed. The expression levels of the DEGs were validated in human GC tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A set of 689 DEGs were identified in GC tissues, as compared with normal tissues, including 202 upregulated DEGs and 487 downregulated DEGs. The KEGG pathway analysis suggested that various pathways may play important roles in the pathology of GC, including pathways related to protein digestion and absorption, extracellular matrix-receptor interaction, and the metabolism of xenobiotics by cytochrome P450. The PPI network analysis indicated that the significant hub proteins consisted of SPP1, TOP2A and ARPC1B. RT-qPCR validation indicated that the expression levels of the top 10 most significantly dysexpressed genes were consistent with the illustration of the integrated analysis. The present study yielded a reference list of reliable DEGs, which represents a robust pool of candidates for further evaluation of GC pathogenesis and treatment.

KRAS and BRAF mutations in serum exosomes from patients with colorectal cancer in a Chinese population.

The efficacy of epidermal growth factor receptor- targeted therapy is significantly associated with Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-raf serine/threonine kinase proto-oncogene (BRAF) mutation in patients with colorectal cancer (CRC), for which the standard gene testing is currently performed using tumor tissue DNA. The aim of the present study was to compare the presence of KRAS and BRAF mutations in the serum exosome and primary tumor tissue from patients with CRC. Genomic DNA were extracted from the tumor tissues of 35 patients with histologically-confirmed CRC and exosomal mRNA were obtained from peripheral blood, which were collected from the corresponding patients prior to surgery. Three mutations in the KRAS gene (codons 12, 13 and 61) and a mutation in the BRAF gene (codon 600) were detected using a polymerase chain reaction-based sequencing method and their presence were compared between tumor tissues and the matched serum exosomes. The KRAS mutation rates in tumor tissues and the matched serum exosomes were 57.6 and 42.4%, respectively, which was not significantly different (P=0.063). The detection rate of the BRAF mutation was 24.2 and 18.2% in tumor tissues and the matched serum exosomes, respectively, and there was no significant difference (P=0.500). The patients with CRC that had a KRAS mutation of codon 12 in exon 2 in their tumor tissues and serum exosomes were significantly older compared with those without this mutation (tumor tissue, P=0.002; serum exosome, P=0.022). The sensitivity of KRAS and BRAF mutation detection using exosomal mRNA was 73.7 and 75%, respectively. The specificity of the detected mutations exhibited an efficiency of 100%, and the total consistency rate was 94.9 and 93.9% for KRAS and BRAF mutations, respectively. These results suggested that serum exosomal mRNA may be used as a novel source for the rapid and non-invasive genotyping of patients with CRC.

Effectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis.

Circulating tumor DNA (ctDNA) can be identified in the peripheral blood of patients and harbors the genomic alterations found in tumor tissues, which provides a noninvasive approach for detection of gene mutations. We conducted this meta-analysis to investigate whether ctDNA can be used for monitoring KRAS gene mutations in colorectal cancer (CRC) patients. Medline, Embase, Cochrane Library and Web of Science were searched for the included eligible studies in English, and data were extracted for statistical analysis according to the numbers of true-positive (TP), true-negative (TN), false-positive (FP) and false-negative (FN) cases. Sensitivity, specificity and diagnostic odds ratio (DOR) were calculated, and the area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. After independent searching and reviewing, 21 studies involving 1,812 cancer patients were analyzed. The overall sensitivity, specificity and DOR were 0.67 (95% confidence interval [CI] =0.55-0.78), 0.96 (95% CI =0.93-0.98) and 53.95 (95% CI =26.24-110.92), respectively. The AUROC was 0.95 (95% CI =0.92-0.96), which indicated the high diagnostic accuracy of ctDNA. After stratified analysis, we found the higher diagnostic accuracy in subgroup of patients detected in blood sample of plasma. The ctDNA may be an ideal source for detection of KRAS gene mutations in CRC patients with high specificity and diagnostic value.

A transcriptome profile in hepatocellular carcinomas based on integrated analysis of microarray studies.

BACKGROUND: Despite new treatment options for hepatocellular carcinomas (HCC) recently, 5-year survival remains poor, ranging from 50 to 70%, which may attribute to the lack of early diagnostic biomarkers. Thus, developing new biomarkers for early diagnosis of HCC, is extremely urgent, aiming to decrease HCC-related deaths. METHODS: In the study, we conducted a comprehensive characterization of gene expression data of HCC based on a bioinformatics method. The results were confirmed by real time polymerase chain reaction (RT-PCR) and TCGA database to prove the credibility of this integrated analysis. RESULTS: After integrating analysis of seven HCC gene expression datasets, 1167 differential expressed genes (DEGs) were identified. These genes mainly participated in the process of cell cycle, oocyte meiosis, and oocyte maturation mediated by progesterone. The results of experiments and TCGA database validation in 10 genes was in full accordance with findings in integrated analysis, indicating the high credibility of our integrated analysis of different gene expression datasets. ASPM, CCT3, and NEK2 was showed to be significantly associated with overall survival of HCC patients in TCGA database. CONCLUSION: This method of integrated analysis may be a useful tool to minish the heterogeneity of individual microarray, hopefully outputs more accurate HCC transcriptome profiles based on large sample size, and explores some potential biomarkers and therapy targets for HCC.

Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene.

BACKGROUND: Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC. METHODS: We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell. RESULTS: The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P < 0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line. CONCLUSION: MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.

[Histone deacetylase inhibitor MS-275 treatment alters immune molecule content and categories in hepatocarcinoma exosomes].

OBJECTIVE: To investigate the effects of the histone deacetylase inhibitor, MS-275, on the immune molecule content and categories in hepatocarcinoma exosomes. METHODS: Exosomes were isolated from the human hepatocarcinoma cell lines, HepG2 and Hep3b, and purified by a combination technique of ultrafiltration centrifugation and sucrose gradient ultracentrifugation. The expressions of heat shock protein (HSP)70, human leukocyte antigen (HLA)-I, HLA-DR, cluster of differentiation (CD) 80 and NY-ESO-1 on exosomes were analyzed with immunoelectron microscopy and Western blotting before and after MS-275 treatment. Intergroup differences were statistically analyzed by the Student's paired t-test. RESULTS: MS-275 treatment of both HepG2 and Hep3b cell types significantly increased the numbers of exosomes, their total protein content, and expression of HSP70, HLA-I and CD80 (per 100 exosomes), as compared to non-treated cells (all, P less than 0.01). MS-275 was also found to induce de novo expression of HLA-DR, but had no significant effect on NY-ESO-1 expression (P more than 0.05). The findings from immunoelectron microscopy confirmed those from Western blotting. CONCLUSION: The histone deacetylase inhibitor, MS-275, can significantly alter the immune molecule content and categories in exosomes of hepatocarcinoma cells. The differential expression profile may reflect an anti-cancer immune response and represent molecular targets for novel anti-hepatoma therapeutic or preventative strategies.

Transcriptional control of Flt3 ligand targeted by fluorouracil-induced Egr-1 promoter in hematopoietic damage.

BACKGROUND: Ionizing radiation (IR) activate the early growth response-1 (Egr-1) promoter by production of radical oxygen intermediates (ROIs). Egr-EF, an expression vector pCIneo containing Egr-1 promoter cloned upstream of the cDNA for Flt3 ligand, was used to treat hematopoietic damage. 5-fluorouracil, a commonly used chemotherapeutic agent, cause tumor cell death by producing DNA damage and generating ROIs. We therefore hypothesized that clinically employed chemotherapeutic agents that increase ROIs could also be employed to activate Egr-EF in a chemoinducible gene therapy strategy. The goal of this study was to explore the effect of Flt3 Ligand gene transcription regulated by fluorouracil-induced Egr-1 promoter on hematopoietic recovery. METHODS: Human Flt3 Ligand (FL) cDNA and enhanced green fluorescent protein (EGFP) cDNA were linked together with IRES and inserted into the expression vector pCI-neo under control of the Egr-1 promoter (Egr-EF). The vector was transfected into the HFCL human bone marrow stromal cell line, and these cells were exposed to 5-FU, a chemotherapeutic drug. Expression of FL by HFCL/EF cells after 5-FU treatment was determined with ELISA, western blot and RT-PCR assays. In addition, the effect of FL from HFCL/EF cell culture supernatants on growth of CD34+ cells from cord blood was also studied. HFCL/EF cells were injected into CB-17 combined immunodeficient (SCID) mice with B16 melanoma. 5-FU was given three days after injection of the HFCL/EF cells. In the recipient mice, white blood cell levels in peripheral blood and expression of EGFP and FL in human stromal cells were measured. Tumor volumes in tumor-bearing mice were also measured. RESULTS: 5-FU treatment increased EGFP levels and secreted FL levels in HFCL/EF cells. Supernatants from HFCL/EF cell cultures treated with 5-FU increased CD34+ cell growth significantly. HFCL/EF exhibited an increase in the number of white blood cells after chemotherapy. CONCLUSION: The data presented here support the use of transcriptional control mediated by chemoinducible gene therapy to reduce hematopoietic injury associated with 5-FU.