Single-atom Mo-Co catalyst with low biotoxicity for sustainable degradation of high-ionization-potential organic pollutants.

Single-atom catalysts (SACs) are a promising area in environmental catalysis. We report on a bimetallic Co-Mo SAC that shows excellent performance in activating peroxymonosulfate (PMS) for sustainable degradation of organic pollutants with high ionization potential (IP > 8.5 eV). Density Functional Theory (DFT) calculations and experimental tests demonstrate that the Mo sites in Mo-Co SACs play a critical role in conducting electrons from organic pollutants to Co sites, leading to a 19.4-fold increase in the degradation rate of phenol compared to the CoCl2-PMS group. The bimetallic SACs exhibit excellent catalytic performance even under extreme conditions and show long-term activation in 10-d experiments, efficiently degrading 600 mg/L of phenol. Moreover, the catalyst has negligible toxicity toward MDA-MB-231, Hela, and MCF-7 cells, making it an environmentally friendly option for sustainable water treatment. Our findings have important implications for the design of efficient SACs for environmental remediation and other applications in biology and medicine.

Photo-Deactivation Strategy for Switchable ATRP with the Assistance of Molecular Switches.

Light irradiation is an external stimulus, rapidly developed in switchable atom transfer radical polymerization (ATRP) via photo-activation methods in recent years. Herein, a photo-deactivation strategy is introduced to regulate ATRP with the assistance of photoswitchable hexaarylbiimidozole (HABI). Under visible light irradiation and in the presence of HABI, ATRP is greatly decelerated or quenched depending on the concentration of HABI. Interestingly, with visible light off, ATRP can proceed smoothly and follow a first-order kinetics. Moreover, photo-switchable ATRP alternatively with light off and on is demonstrated. Besides, the mechanism of photo-deactivation ATRP involving radical quenching is proposed in the presence of HABI.

Tailoring Polymerization Controllability and Dispersity Through a Photoswitchable Catalyst Strategy.

Modulating on-demand polymerization is a challenge in synthetic macromolecules. Herein, tailoring polymerization controllability and dispersity during single-electron transfer mediated living radical polymerization (SET-LRP) of methyl methacrylate (MMA) is achieved. Hexaarylbiimidazole (HABI) is employed as a photoswitchable catalyst, allowing reversible control of catalytic activity between an active and inactive state. In the presence of HABI and with the light on (active state), control SET-LRP of MMA follows first-order kinetics, resulting in polymers with a narrow molecular weight distribution. In contrast, polymerization responds to light and reverts to their original uncontrolled state with light off (inactive state). Therefore, repeatable resetting polymerization can be easily performed. The key to photomodulating dispersity is to use an efficient molecular switch to tailor the breadths of dispersity. Besides, the mechanism of HABI-mediated SET-LRP with switchable ability is proposed.

Survival of patients with multidrug-resistant tuberculosis in Central China: a retrospective cohort study.

The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01-2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30-2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.

Gambogic Acid Efficiently Kills Stem-Like Colorectal Cancer Cells by Upregulating ZFP36 Expression.

BACKGROUND/AIMS: Gambogic acid (GA), the main active compound of Gamboge hanburyi, has been reported to be a potential novel antitumor drug. Whether GA inhibits putative cancer stem cells (CSCs), which are considered to be the major cause of cancer treatment failure, remains largely unknown. This study investigated whether GA inhibits the CSCs of colorectal cancer (CRC) and its possible mechanisms. METHODS: We performed CCK8 and tumor sphere formation assays, percentage analysis of both side population and CD133+CD44+ cells, and the detection of stem cells markers, in order to assess the role of GA in inhibiting the stem celllike features of CRC. An mRNA microarray was performed to identify the downstream gene affected by GA and rescue assays were performed to further clarify whether the downstream gene is involved in the GA induced decrease of the stem cell-like CRC population. CRC cells were engineered with a CSC detector vector encoding GFP and luciferase (Luc) under the control of the Nanog promoter, which were utilized to investigate the effect of GA on putative CSC in human tumor xenograft-bearing mice using in vivo bioluminescence imaging. RESULTS: Our results showed that GA significantly reduced tumor sphere formation and the percentages of side population and CD133+CD44+ cells, while also decreasing the expression of stemness and EMT-associated markers in CRC cells in vitro. GA killed stem-like CRC cells by upregulating the expression of ZFP36, which is dependent on the inactivation of the EGFR/ ERK signaling pathway. GFP+ cells harboring the PNanog-GFP-T2A-Luc transgene exhibited CSC characteristics. The in vivo results showed that GA significantly inhibited tumor growth in nude mice, accompanied by a remarkable reduction in the putative CSC number, based on whole-body bioluminescence imaging. CONCLUSION: These findings suggest that GA significantly inhibits putative CSCs of CRC both in vitro and in vivo by inhibiting the activation of the EGFR/ ERK/ZFP36 signaling pathway and may be an effective drug candidate for anticancer therapies.

The spatial response of carbon storage to territorial space composition and landscape pattern changes: A case study of the Fujian Delta urban agglomeration, China.

Understanding the impact mechanisms of territorial space composition and landscape pattern changes on carbon storage is critical to balance the development and utilization of territorial space and the conservation of the ecosystem. Thus, taking the Fujian Delta urban agglomeration (FDUA) of China as an example, this paper analyzed the impact of the transference in territorial space composition and the change in the coupling coordination degree (CCD) of landscape patterns on carbon storage based on the urban-rural gradient and grid scales. Results illustrated that the areas of agricultural, green, and blue spaces continued to decline, while the intensity of economic space expansion increased from 20.86 to 42.45% during 2000-2020. The grids with CCD change of landscape patterns declined mainly (accounting for 64.31%) in the first decade and rose mainly (accounting for 76.79%) in the second decade. The carbon loss of each under rural gradient was gradually serious. The percentage of grids with moderate and significant decrease in carbon storage escalated from 27.83 to 70.21%. Additionally, grids experiencing high carbon loss moved from the northeast coast to the southwest inland. The response of carbon storage change showed that the expansion of agricultural space occupied by economic space played a crucial role in the carbon loss in each urban-rural gradient. The carbon loss caused by supplementing agricultural space with green space increased from the urban to the field. Enhancing the CCD of landscape patterns can boost carbon storage, and the scattering expansion of economic space needs to be avoided. This paper provides a novel perspective to explore the spatial response of carbon storage change to the territorial space composition and landscape pattern evolution, which is important to optimize the territorial space pattern and improve the regional carbon sink capacity.

Dynamic simulation of land use change and habitat quality assessment under climate change scenarios in Nanchang, China.

Investigating habitat quality under different climate scenarios holds significant importance for sustainable land resource management and ecological conservation. In this study, considering Nanchang as a case study, a coupled patch-generating land use simulation (PLUS) and system dynamics (SD) model was employed in the simulation and prediction of land usage under shared socioeconomic pathway (SSP) and representative concentration pathway (RCP) scenarios. To assess the habitat quality in Nanchang from 2000 to 2020 and in 2030 under three diverse climate scenarios, we used the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model to analyze spatial and temporal changes. The findings indicate that the regions of forest land, cultivated land, and grassland in Nanchang City will dramatically decrease by 2030, the construction land will rapidly expand, and the fluctuations in the unutilized land and water area will be minimal. Additionally, the habitat quality declined from 2000 to 2020, and its spatial distributions changed. Zones having a high overall habitat quality were distributed in the mountains, hills, and lake areas, whereas those with relatively low quality were found in cultivated and urban areas. Under three climate scenarios, in 2030, the habitat quality index for Nanchang City will show a decreasing trend, mainly owing to areas with an index of 0.3-0.5 transitioning to <0.3. Considering each scenario, the degree of habitat degradation increased in the order SSP585>SSP245>SSP119. The findings of this study will inform high-quality development and biodiversity conservation in Nanchang City.

Gestational exposure to PM2.5 disrupts fetal development by suppressing placental trophoblast syncytialization via progranulin/mTOR signaling.

Recent epidemiological and animal studies have indicated that ambient fine particulate matter (PM2.5) exposure during pregnancy is closely associated with intrauterine growth restriction (IUGR). However, the underlying mechanisms remain to be revealed. In this study, we found that gestational exposure to PM2.5 significantly decreased fetal weight and crown-rump length in mice, accompanied by insufficient placental trophoblast syncytialization and increased expression of progranulin (PGRN) in mice placenta. Administering PGRN neutralizing antibody to pregnant mice alleviated growth restriction and insufficient placental trophoblast syncytialization caused by PM2.5, accompanied with suppressed activation of the mTOR signaling pathway. Furthermore, in vitro experiments using human placental BeWo cells showed that 10 µg·mL-1 PM2.5 activated PGRN/mTOR signaling and suppressed forskolin-induced cell fusion, which was blocked by knockdown of PGRN. Taken together, our results demonstrated that PM2.5 exposure during pregnancy inhibited placental trophoblast syncytialization by activating PGRN/mTOR signaling, leading to abnormal placental development and IUGR. This study reveals a novel mechanism underlying the developmental toxicity of PM2.5 exposure during pregnancy.

Interlaminar Properties of Prepregs Reinforced with Multiwalled Carbon Nanotubes/Graphene Oxide.

Carbon-fiber-reinforced polymer (CFRP) composites are widely used in industries such as aerospace due to their lightweight nature and high strength. However, weak interfacial bonding strength is one of the main problems of resin-based composites. In this study, a prepreg was prepared by melt mixing. By dispersing nanoreinforcement particles in the resin, the interlaminar shear strength of the CFRP was increased by approximately 23.6%. When only 0.5 wt% multiwalled carbon nanotube (MWCNT) was used for reinforcement, scanning electron microscopy (SEM) micrographs showed that cracks were hindered by the MWCNTs during propagation, causing crack deflection. At the same time, the mechanism of MWCNTs pulling out increased the energy required for crack propagation. When only 0.5 wt% graphene oxide (GO) was added, the reinforcement effect was inferior to that of using the same amount of MWCNTs. The laminar structure formed by GO and the resin matrix adhered to the carbon fiber surface, reducing the degree of destruction of the resin matrix, but its hindering effect on crack propagation was weak. When 0.5 wt% of MWCNT and GO mixture was added, the interlayer shear strength increased from 55.6 MPa in the blank group to 68.7 MPa. The laminar structure of GO provided a platform for the MWCNTs to form a mesh structure inside its matrix. At the same time, the tubular structure of the MWCNTs inhibited the stacking of GO, providing better dispersion and forming a synergistic enhancement effect.

Comparative ecological network pattern analysis: a case of Nanchang.

Urban-ecological landscape connectivity and pattern optimization can significantly enhance biodiversity and sustainable development capacity, which play an important role in continued ecosystem functioning. Previous studies identified ecological sources based on the area threshold method or combination with morphological spatial pattern analysis and the landscape connectivity index (CMSPACI) method, but few studies have compared the advantages, disadvantages, and applicability of the two methods. In this paper, taking Nanchang as the study area, we address the ecological sources via area threshold and the CMSPACI method. Then, the minimum cost distance method is used to generate potential corridors of different methods, and the differences in ecological networks are analyzed. Finally, the circuit theory is used to identify barriers, and we provide targeted recommendations for ecological network pattern optimization in the study area. The results show that (1) the ecological sources extracted by different methods are different. The ecological sources extracted by the area threshold are far away from the surrounding sources, and the landscape connectivity is low. The ecological sources identified by the CMSPACI method are closely related to the surrounding sources, and the landscape connectivity is high. (2) Compared with the area threshold method, the habitat quality of corridors under the CMSPACI method is better, and the interaction intensity between patches is larger. (3) There is little difference in the number of ecological barriers under different methods; all of them are located between patches or on the edge of patches, and most of them are roads or construction land. Overall, the area threshold method is simpler. Ecological sources can be effectively addressed through the CMSPACI method, and the landscape connectivity of the ecological network will be better. This study provides an important reference for the selection of ecological sources in the construction of ecological networks.

Outcomes of Laparoscopic Surgery for Mucinous Colorectal Adenocarcinoma.

Background: Mucinous colorectal adenocarcinoma (MAC) has a higher incidence of local extension, leading to lower overall resection rates. Few studies have investigated the outcomes of laparoscopic surgery for MACs to date. Therefore, we aimed to elucidate the validity of laparoscopic surgery for mucinous adenocarcinoma (MAC). Methods: This study analyzed short-term and long-term outcomes between laparoscopic and open surgery for MACs from 2008 to 2018. Multivariate analyses were used to define prognostic factors of overall survival (OS) and disease-free survival (DFS). Results: Patients in the laparoscopy (LAP) group had significantly less blood loss, fewer days to first flatus and to diet, and shorter length of hospital stay. The 3-year and 5-year DFS rates for all stages combined were 65.7% and 62.5% in the LAP group compared with 60.5% and 57.6% in the open (OPEN) surgery group (P = .521). The 3-year and 5-year OS rates for all stages combined were 72.3% and 67.3% in the LAP group compared with 72.6% and 67.8% in the OPEN group (P = .934). OS and DFS in stage II, stage III, and pathological T4 (pT4) stage patients who underwent laparoscopic surgery did not differ from patients who underwent open surgery. Multivariate analysis showed that stage pT4, pN2, and carcinoembryonic antigen (CEA) were significant predictors of OS. Independent factors, including intraoperative blood transfusion, stage pT4, pN2, CEA, and CA19-9, carbohydrate antigen 19-9, have a great effect on DFS. Conclusions: Laparoscopic surgery is a safe and feasible option for mucinous colorectal AC, which provides faster postoperative recovery and less intraoperative blood loss.

Risk Factors for Recurrence of Radically Resected Mucinous Colorectal Adenocarcinoma.

BACKGROUND: Mucinous adenocarcinoma (MA) is a subtype of colorectal cancer (CRC) associated with a higher incidence of local extension and worse survival compared to non-mucinous adenocarcinoma, but few studies have investigated surgery-related predictors for recurrence of MA. Therefore, we aimed to elucidate the predictors for local recurrence and remote metastasis of MA after surgery. PATIENTS AND METHODS: This study retrospectively analyzed 162 patients with mucinous colorectal adenocarcinoma (MAC) after radical resection. Analysis variables included demographics, clinical indicators, pathologic stage, surgical procedure, adjuvant therapy, and recurrence. Univariate and multivariate analyses were performed to investigate the risk factors for local and distant tumor relapse. RESULTS: A total of 162 patients (86 male) with a mean age of 58.26 years were included; 70.37% of patients had colonic tumors, and 29.63% had rectal tumors. The 5-year disease-free survival (DFS) rates for these patients were as follows: 100% for TNM stage I, 71.2% for stage II, and 47.8% for stage III. Five-year DFS rates of MAC, colonic and rectal MA were 62.0%, 65.8%, and 51.7%, respectively. Local recurrence occurred in 38 patients and distant metastasis in 33 patients. In univariate analysis, predictors for local recurrence of MAC were intraoperative blood loss, intraoperative transfusion, and N2 stage; and predictors for distant metastasis were male sex, CA199, CEA, intraoperative blood loss, T4 stage, and N2 stage. In multivariate analysis, predictors for local recurrence of MAC were intraoperative transfusion (P=0.04, OR=4.175) and N2 stage (P=0.000, OR=5.291), and predictors for distant metastasis were male sex (P=0.049, OR=2.410), CA199 (P=0.02, OR=1.003), and T4 stage (P=0.007, OR=4.006). CONCLUSION: Intraoperative transfusion and N2 stage were significant predictors for local recurrence. Male sex, CA199, and T4 stage were significant predictors for distant metastasis. Knowledge of the risk factors for postoperative recurrence provides a basis for logical approaches to treatment and follow-up of MAC.

γ-Fe2O3 nanoparticles stabilized by holey reduced graphene oxide as a composite anode for lithium-ion batteries.

Integrating nanoscale active materials on conductive holey reduced graphene oxide (RGO) framework is an effective strategy to synthesize composite electrode materials for advanced lithium-ion batteries. Herein, a composite of γ-Fe2O3 nanoparticles stabilized by the engineered holes on RGO was successfully synthesized by using a facile in-situ etching route, which exhibited high lithium storage performance. The fundamental insight of its enhancement mechanism was discussed. This work offers a newly route to synthesize the composite of holey RGO confined metal oxide nanoparticles for the applications in lithium ion batteries and beyond.

PD-L1 promotes colorectal cancer stem cell expansion by activating HMGA1-dependent signaling pathways.

PD-L1 is critical for tumor cell escape from immune surveillance by inhibiting T cell function via the PD-1 receptor. Accumulating evidence demonstrates that anti-PD-L1 monoclonal antibodies might potently enhance antitumor effects in various tumors, but the effect of PD-L1 on colorectal cancer stem cells (CSCs) remains unclear. We observed high PD-L1 expression in CD133+CD44+ colorectal CSCs and CSC-enriched tumorspheres. Altering PD-L1 expression promoted colorectal CSC self-renewal by increasing the expression of stemness genes, the CD133+CD44+ cell population sizes and the ability to form tumorspheres. Additionally, PD-L1 expression was markedly increased in chemoresistant colorectal cancer (CRC) cells in vitro and in vivo. More importantly, PD-L1 enhanced CRC cell tumorigenicity in nude mice; the inoculation of 1 × 104 cells resulted in high tumor formation efficiency. Mechanistically, PD-L1 directly interacted with HMGA1, and HMGA1 upregulation by PD-L1 activated HMGA1-dependent pathways, including the PI3K/Akt and MEK/ERK pathways, and promoted CSC expansion. HMGA1 downregulation rescued the PD-L1-induced phenotypes, highlighting the role of HMGA1 in PD-L1-mediated colorectal CSC self-renewal. Moreover, PD-L1 expression was correlated with the expression of CSC markers and HMGA1 in clinical CRC specimens. Thus, PD-L1 could crucially contribute to the maintenance of CSC self-renewal by activating HMGA1-dependent signaling pathways.

Long non­coding RNA 00152 functions as a competing endogenous RNA to regulate NRP1 expression by sponging with miRNA­206 in colorectal cancer.

Colorectal cancer (CRC) is the third most common type of cancer; however, the molecular mechanisms underlying colorectal tumor metastasis and growth remain elusive. Recently, accumulating evidence has indicated that long non­coding RNAs (lncRNAs) play a critical role in CRC progression and metastasis; however, the biological role and clinical significance of lncRNA 00152 (lnc00152) in CRC remains largely unknown. Thus, in this study, lnc00152 expression was measured in 80 human CRC tissue samples, 40 non­cancerous tissue samples, and 3 CRC cell lines (SW480, SW620 and LoVo) using RT­qPCR. We examined the effects of lnc00152 on CRC cells following transfection with lnc00152 overexpression plasmid or respective siRNA in vitro and in vivo. Luciferase assays revealed the mechanism driving competitive endogenous RNA (ceRNA). We identified that lnc00152 was aberrantly overexpressed in colorectal tumors and cancer cells and that lnc00152 was modulated by miRNA­206. lnc00152 overexpression enhanced the proliferative and invasive ability of CRC cells in vitro, promoted tumor growth in vivo, and was associated with the shorter overall survival of patients with CRC. In addition, lnc00152 overexpression promoted epithelial-mesenchymal transition (EMT) and increased neuropilin­1 (NRP1) expression in the CRC cells. By contrast, lnc00152 silencing exerted a counteractive effect. Collectively, these findings demonstrate the critical role of lnc00152 in tumor growth and progression in CRC, and identify a novel therapeutic target associated with CRC development and progression.

Dietary modulation of mitochondrial DNA deletions and copy number after chemotherapy in rats.

Mitochondrial DNA (mtDNA) is particularly susceptible to mutation by alkylating agents, and mitochondrial damage may contribute to the efficacy and toxicity of these agents. We found that folate supplementation decreased the frequency of the "common deletion" (4.8kb, bases 8103-12,936) in liver from untreated rats and from animals treated with cyclophosphamide but not 5-fluorouracil (5-FU). The relative abundance of mitochondrial DNA was greater after chemotherapy but there was no effect of diet. Rats fed with a purified diet had fewer mitochondrial deletions than those maintained on a cereal-based diet after chemotherapy. These results indicate that diet can modulate the extent of mitochondrial damage after cancer chemotherapy, and that folic acid supplementation may be protective against mitochondrial DNA deletions.

Nucleic acid deletions and copy number in rats.

Rats fed either a cereal-based or purified diet of variable folate content (deficient, replete, or supplemented) inadvertently were infected with sialodacryoadenitis virus, which resulted in an increased frequency of hepatic mitochondrial DNA (mtDNA) deletions that persisted for three weeks after the period of acute signs of disease. The amount of the "common deletion" (4.8 kb, bases 8103-12937) in liver was measured by quantitative co-amplification of the mitochondrial D-loop and the mitochondrial deletion, using a real-time quantitative polymerase chain reaction assay. The relative abundance of mtDNA was determined by co-amplifying mitochondrial D-loop versus the rat beta-actin gene. Virus-infected rats had more mtDNA deletions (P < 0.0001) and higher copy number (P < 0.0001) than did uninfected animals. There was no effect of diet on frequency of deletions. Diet affected mtDNA relative abundance in the infected, but not the uninfected rats. Relative abundance was higher (P = 0.004) in rats of the high folate group than in rats of the low-folate or folate-replete groups, and was significantly higher in rats of the cereal diet group than that in those of the purified diet group. In conclusion, sialodacryoadenitis virus infection in rats was associated with increased frequency of hepatic mtDNA deletions. Thus, sialodacryoadenitis virus infection mitigated biological processes in the liver of rats, and mtDNA damage was modulated by diet.

Effect of vitamin B12, folate, and dietary supplements on breast carcinoma chemotherapy--induced mucositis and neutropenia.

BACKGROUND: Although patients with malignant disease frequently use dietary supplements, the effects of these agents with regard to chemotherapy are unclear. Therefore, the authors investigated the influence of vitamin B12, folate, and nutritional supplements on chemotherapy-induced toxicity. METHODS: Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts. Toxicity was evaluated by measuring absolute neutrophil counts and the frequency and severity of oral mucositis. RESULTS: Of the 49 women who submitted questionnaires, 35 (71%) took a combined total of 165 supplements. Compared with patients in a previous study (performed in 1990), patients in the current study had dramatically increased serum folate levels. Initial neutrophil count, but not type of chemotherapy, patient age, or serum vitamin B12 level, was predictive of nadir absolute neutropenia and the decrease from initial neutrophil count to nadir (Nfall). After adjusting for initial neutrophil count, Nfall was found to be lower for women who were taking supplements compared with women who were not taking supplements (P = 0.01) and for women who were taking multivitamins (P = 0.01) or vitamin E (P = 0.03). Women with serum folic acid levels < 20 ng/mL had a smaller decrease in neutrophil count after chemotherapy than did women with higher folate levels (P = 0.04). No significant association between oral mucositis and initial neutrophil count, nadir neutrophil count, Nfall, age, vitamin B12 level, or folate level was found. CONCLUSIONS: The decrease in neutrophil count caused by chemotherapy was ameliorated by dietary supplementation with a multivitamin or vitamin E. In contrast, high serum folate levels were associated with the exacerbation of this decrease in neutrophil count.

Diet modulates the toxicity of cancer chemotherapy in rats.

The effects of diet and folate status on cyclophosphamide or 5-fluorouracil toxicity were studied in Fischer 344 rats maintained on either a cereal-based diet or a purified diet (AIN-93G). The rats fed the purified diet were divided into 3 groups: folate deficient (no dietary folic acid), folate replete (2 mg folic acid/kg diet), and high folate (2 mg folic acid/kg diet plus 50 mg/kg body weight folic acid intraperitoneally daily). The LD50 for cyclophosphamide was significantly higher for the cereal diet than for the purified diets, but there was no difference among the purified diets. Deaths were predicted by dose, diet, white blood cell count, and BUN on Day 4 after treatment. In the saline-treated rats fed the purified diet, hepatic total glutathione levels increased in the following order: folate deficient < folate replete < high folate. There was no significant difference in aldehyde dehydogenase activities or of microsomal P450 levels in livers from rats on the different diets. In the rats treated with 5-fluorouracil, the high folate rats developed more severe anemia, azotemia, and leukopenia than the other groups. Weight, white blood cell count, hematocrit, and BUN were important predictors of death. The kidneys from rats fed the cereal-based diet were histologically normal, but rats ingesting the purified diet had increasing renal pathology that correlated with folate intake. These results indicate that diet has an important influence on the toxicity of cyclophosphamide and 5-fluorouracil and that folate status modulates hepatic glutathione levels, which is a major cellular defense against oxidant and alkylating agent damage.