Correlation between the development of phage resistance and the original antibiotic resistance of host bacteria under the co-exposure of antibiotic and bacteriophage.

Bacteriophages (phages) are viruses capable of regulating the proliferation of antibiotic resistant bacteria (ARB). However, phages that directly cause host lethality may quickly select for phage resistant bacteria, and the co-evolutionary trade-offs under varying environmental conditions, including the presence of antibiotics, remains unclear as to their impact on phage and antibiotic resistance. Here, we report the emergence of phage resistance in three distinct E. coli strains with varying resistance to ß-lactam antibiotics, treated with different ampicillin (AMP) concentrations. Hosts exhibiting stronger antibiotic resistance demonstrated a higher propensity to develop and maintain stable phage resistance. When exposed to polyvalent phage KNT-1, the growth of AMP-sensitive E. coli K12 was nearly suppressed within 18 h, while the exponential growth of AMP-resistant E. coli TEM and super-resistant E. coli NDM-1 was delayed by 12 h and 8 h, respectively. The mutation frequency and mutated colony count of E. coli NDM-1 were almost unaffected by co-existing AMP, whereas for E. coli TEM and K12, these metrics significantly decreased with increasing AMP concentration from 8 to 50 µg/mL, becoming unquantifiable at 100 µg/mL. Furthermore, the fitness costs of phage resistance mutation and its impact on initial antibiotic resistance in bacteria were further examined, through analyzing AMP susceptibility, biofilm formation and EPS secretion of the isolated phage resistant mutants. The results indicated that acquiring phage resistance could decrease antibiotic resistance, particularly for hosts lacking strong antibiotic resistance. The ability of mutants to form biofilm contributes to antibiotic resistance, but the correlation is not entirely positive, while the secretion of extracellular polymeric substance (EPS), especially the protein content, plays a crucial role in protecting the bacteria from both antibiotic and phage exposure. This study explores phage resistance development in hosts with different antibiotic resistance and helps to understand the limitations and possible solutions of phage-based technologies.

Heavy metals immobilization of ternary geopolymer based on nickel slag, lithium slag and metakaolin.

To solve heavy metals leaching problem in the utilization of various industrial solid wastes, this work investigated the heavy metals immobilization of ternary geopolymer prepared by nickel slag (NS), lithium slag (LS), and metakaolin (MK). Compressive strength was measured to determine the optimum and appropriate mix proportions. The leaching characteristics of typical heavy metals (Cu (Ⅱ), Pb (Ⅱ), and Cr (Ⅲ)) in acid, alkali, and salt environments were revealed by Inductively Coupled Plasma (ICP). The heavy metals immobilization mechanism was explored by Mercury Intrusion Porosimetry (MIP), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) tests. The experimental results show that the group with a mass ratio of NS, LS and MK of 1:1:8 exhibits the highest compressive strength, which reaches 69.1 MPa at 28 d. The ternary geopolymer possesses a desirable capacity for immobilizing inherent heavy metals, where the immobilization rates of Cu and Pb reach 96.69 %, and that of Cr reaches 99.97 %. The leaching concentrations of Cr and Pb increase when the samples are exposed to acidic and alkaline environments. Cu and Pb are mainly physically encapsulated in geopolymer. Additionally, immobilization of Cr mainly involves physical encapsulation and chemical bonding.

Effects of different planting distances and fertilizer use on the remediation of farmland contaminated with Cd by intercropping Cucurbita moschata and Amaranthus hypochondriacus L.

Selecting suitable agronomic measures can strengthen the application of intercropping in the remediation of cadmium (Cd)-contaminated soil. In this study, the effects of different planting densities and fertilizer applications on the crop growth and Cd absorption of a pumpkin (Cucurbita moschata)-Amaranthus hypochondriacus L. intercropping system was determined. The goal was to provide enhanced means and a scientific basis for the promotion and application of this intercropping system. The Cd content of pumpkin in different planting systems was lower than the national food safety standard (0.05 mg kg-1). In the IN-1 (4 pumpkin plants intercropped with 200 A. hypochondriacus plants) and IN-2 (4 pumpkin plants intercropped with 400 A. hypochondriacus plants) intercropping systems, the bioconcentration amount (BCA) per plant of Cd in A. hypochondriacus increased by 32.43% and 25.25%, respectively, compared with that of the monocropping system (P < 0.05). The IN-2 system had the highest equivalent ratio of heavy metal removal (3.08), indicating that this model had a substantial advantage for removing Cd. The land equivalent ratio of IN-1 (2.89) and IN-2 (2.60) was significantly higher than that of other intercropping systems, indicating that these two models had obvious yield advantages. In our study, chicken manure was the best at promoting the growth and yield of the two plants and sludge treatment significantly enhance Cd absorption of A. hypochondriacus. In general, intercropping four pumpkin plants with 400 A. hypochondriacus plants and applying chicken manure fertilizer can strengthen the application of this intercropping system in Cd-contaminated soil.

Exploration of the Compressive Strength and Microscopic Properties of Portland Cement Taking Attapulgite and Montmorillonite Clay as an Additive.

The effects of attapulgite and montmorillonite calcinated at 750 °C for 2 h as supplementary cementing materials (SCMs) on the working properties, mechanical strength, phase composition, morphology, hydration and heat release of ordinary Portland cement (OPC) were studied. The results show that pozzolanic activity increased with time after calcination, and with the increase in content of calcined attapulgite and calcined montmorillonite, the fluidity of cement paste exhibited a downward trend. Meanwhile, the calcined attapulgite had a greater effect on the decrease in the fluidity of cement paste than calcined montmorillonite, and the maximum reduction was 63.3%. Within 28 days, the compressive strength of cement paste with calcined attapulgite and montmorillonite was higher than that of the blank group in the later stage, and the optimum dosages of calcined attapulgite and montmorillonite were 6% and 8%, respectively. In addition, the compressive strength of these samples reached 85 MPa 28 days later. The introduction of calcined attapulgite and montmorillonite increased the polymerization degree of silico-oxygen tetrahedra in C-S-H gels during cement hydration, thereby contributing to accelerating the early hydration process. In addition, the hydration peak of the samples mixed with calcined attapulgite and montmorillonite was advanced, and the peak value was lower than that of the control group.

High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration.

Purpose: To elucidate the clinical and prognostic role of PDZ and LIM domain protein (PDLIM) genes and the association to epithelial-mesenchymal transition (EMT) and immune cell infiltration in patients with prostate cancer (PRAD). Methods: The data of RNA-seq, DNA methylation, and clinical features of PRAD patients were collected from The Cancer Genome Atlas (TCGA) database to define the prognostic value of PDLIM gene expression and the association with EMT and immune cell infiltration. A tissue microarray including 134 radical prostatectomy specimens was served as validation by immunohistochemistry (IHC) staining analysis. Results: The mRNA levels of PDLIM1/2/3/4/6/7 were significantly downregulated, while PDLIM5 was upregulated in PRAD (P < 0.05). High expression of PDLIM2 mRNA suggests poor progression free interval in PRAD patients. DNA methylation of PDLIM2 was correlated with its mRNA expression level, and that the cg22973076 methylation site in PDLIM2 was associated with shorter PFI (P < 0.05) in PRAD. Single-sample gene-set enrichment and gene functional enrichment results showed that PDLIM2 was correlated with EMT and immune processes. Spearman's test showed a significant correlation with six reported EMT signatures and several EMT signature-related genes. Tumor microenvironment analysis revealed that the PDLIM2 mRNA expression was positively correlated with the immune score, stromal score, and various tumor infiltrating immune cells. Additionally, the results showed that patients in the high-PDLIM2 mRNA expression group may be more sensitive to immune checkpoint blockade therapy. Finally, IHC analysis further implicated the protein level of PDLIM2 was upregulated in PRAD and acts as a novel potential biomarker in predicting tumor progression. Conclusion: Our study suggests that PDLIM family genes might be significantly correlated with oncogenesis and the progression of PRAD. PDLIM2 correlated with EMT and immune cell infiltration by acting as an oncogene in PRAD, which may serve as a potential prognostic biomarker for PRAD patients.

Expression and clinical significance of lncRNA BC041954 in ovarian cancer.

Ovarian cancer (OC) is a highly lethal disease among all gynecologic malignant tumor types. Accumulating studies have indicated that certain long non-coding RNAs (lncRNAs) serve important roles in the development and progression of OC. In a previous study by our group, lncRNA BC041954 was identified as one of the most upregulated lncRNAs in OC. In the present study, the clinical significance of lncRNA BC041954 in OC was evaluated. The expression of BC041954 was detected in OC and non-tumor tissue (NT) samples using reverse transcription-quantitative PCR. Furthermore, the association between BC041954 and clinicopathological variables was analyzed using the Chi-square test. Survival was determined using Kaplan-Meier analysis. The prognostic significance of BC041954 was evaluated using univariate and multivariate logistic regression analyses. MicroRNA (miRNA)-lncRNA and miRNA-mRNA pairs were used to construct the lncRNA-miRNA-mRNA competing endogenous RNA network with an in-house Perl script. BC041954 expression was increased in 103 OC tissues as compared with that in NT tissues. Upregulated BC041954 expression was significantly associated with the International Federation of Gynecology and Obstetrics stage and distant metastasis. Kaplan-Meier analysis demonstrated that patients with high BC041954 expression had lower overall survival (OS). In the multivariate logistic regression analysis, BC041954 was also identified as an independent poor prognostic factor for OS in patients with OC. The results suggested that overexpression of the lncRNA BC041954 is a poor prognostic indicator in patients with OC.

The Mediating Role of Placental Weight Change in the Association Between Prenatal Exposure to Thallium and Birth Weight: A Prospective Birth Cohort Study.

Background: Previous studies have demonstrated the embryotoxicity and fetotoxicity of thallium (Tl). However, the effects of prenatal exposure to Tl on birth weight and placental weight and the mediating role of placental weight in the association of Tl with birth weight remain unclear. Methods: We recruited 2,748 participants from the ongoing Prenatal Environment and Offspring Health Cohort (PEOH Cohort) study, which was initiated in 2016 in Guangzhou, China. The Tl concentrations in maternal urine samples collected during the first and third trimester were determined by inductively coupled plasma mass spectrometry. Birth weight and placental weight were extracted from maternal medical records. Results: Pregnant women exposed to the highest tertile of Tl in the first trimester (ß = -42.7 g, 95% CI: -82.3, -3.1 g) and third trimester (ß = -50.6 g, 95% CI: -99.0, -2.3 g) had babies with lower birth weights than those exposed to the lowest tertile. We also found significant negative associations of exposure to Tl concentrations in the first and third trimester with placental weight. Mediation analyses showed that 50.3% (95% CI: 15.9, 79.2%) and 33.5% (95% CI: 1.3, 80.3%) of the effects of Tl exposure in the first and third trimester on birth weight were mediated by decreased placental weight. Conclusion: Our results suggest that prenatal exposure to Tl is negatively associated with birth weight and that this association may be mediated by decreased placental weight.

The mediation effect of placental weight change in the association between prenatal exposure to selenium and birth weight: Evidence from a prospective birth cohort study in China.

Selenium (Se) is an essential element and also toxic at an excessive level for human body. However, few studies have investigated adverse effects of Se exposure on birth weight and placental weight. METHODS: All participants were selected from the Prenatal Environment and Offspring Health cohort conducted in 2016 in Guangzhou, China. Se in each participant was measured by inductively coupled plasma mass spectrometry in their urine samples. The urinary Se concentrations were corrected by creatinine and transformed by natural logarithm (ln-Se). Multiple-linear regression models were applied to estimate the associations among Se exposure levels, placenta weight, and birth weight. RESULTS: A total of 2758 mother-newborn pairs were included in this study. Each interquartile range (0.53 µg/g creatinine) increment in urine ln-Se concentration during the first trimester was associated with a mean 21.7 g (95% CI = -41.3g to -2.1g) decrease in birth weight and 3.6g (95% CI = -6.3g to -0.9g) decrease in placental weight. Compared with the lowest quartile (Q1) of ln-Se concentrations during the first trimester, significantly lower birth weight was found in the highest quartile (Q4) (ß = -45.7g; 95% CI = -90.7g to -0.7g). Similar dose-response associations with birthweight and placental weight were found for Se exposure during the third trimester. Mediation analyses showed that 44.2% and 18.2% of the effects of Se exposure in first and third trimester on birth weight were mediated by decreased placental weight, respectively. CONCLUSION: Maternal Se exposure during pregnancy was negatively associated with birth weight, the reduction of placental weight may partially mediate the association of prenatal Se exposure with birth weight.

Tim-3 suppresses autoimmune hepatitis via the p38/MKP-1 pathway in Th17 cells.

T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates T-cell suppression in various autoimmune diseases, such as chronic inflammatory liver disease. However, the regulatory effect of Tim-3 on Th17 cells in autoimmune hepatitis (AIH) is incompletely understood. Here, we studied the expression and function of Tim-3 in T cells in AIH patients and in a Con A (concanavalin A)-induced mouse AIH model. We report that the frequency of CD4+ Tim-3+ T cells in peripheral blood samples of AIH patients was lower than that in the control group. The p38/MKP-1 and p-JNK pathways were activated, and the expression of interleukin-17A protein was elevated in patients with AIH. Furthermore, the extent of pathological damage in the livers of mice with a blocked Tim-3 signaling pathway (anti-Tim-3 group) was markedly increased and correlated with elevated alanine aminotransferase and aspartate aminotransferase levels. In addition, the frequency of CD4+ IL-17+ T (Th17) cells in the anti-Tim-3 group was increased, while that in mice with blocked p38 activity was decreased. Finally, the expression of MKP-1 (p-p38) gradually increased in the control, Con A, and anti-Tim-3 groups, but the levels of interleukin-17A were decreased in the p38-blocked group. In summary, our results suggest that Tim-3 suppresses AIH by regulating Th17 cells through the p38/MKP-1 pathway.

Association between maternal thallium exposure and risk of gestational diabetes mellitus: Evidence from a birth cohort study.

BACKGROUND: The adverse effects of TI exposure on pregnant women are still unclear, especially regarding the risk of gestational diabetes mellitus (GDM) Objective: We explored the association between maternal urinary Tl burden and the risk of GDM. METHODS: A subsample of 1789 pregnant women were enrolled who provided spot urine samples before the diagnostic 75-g oral glucose tolerance test. Urinary Tl concentration was measured using inductively coupled plasma mass spectrometry. Logistic regression and covariance analysis were carried out to estimate the association between Tl exposure and GDM risk. RESULTS: The median of urinary Tl concentration was 0.382 µg/L or 0.525 µg/g creatinine (CC-Tl). There were 437 (24.4%) participants who were diagnosed with GDM, and the urinary CC-Tl concentrations of pregnant women with GDM were higher than that of pregnant women without GDM [0.548 (0.402, 0.788) vs 0.518 (0.356, 0.724), p = 0.014]. After adjusting for the relevant covariates, an association between urinary Tl concentrations and GDM was found. In comparison to the pregnant women in the lowest quartile of urinary CC-Tl concentration, the pregnant women in the highest quartile had a higher risk of GDM [OR (95% CI) = 1.44 (1.03, 2.02), p-trend = 0.055]. If limited to the pregnant women without family history of diabetes, the results were still robust [OR (95% CI) = 1.59 (1.11, 2.30), p-trend = 0.012]. CONCLUSION: Urinary CC-Tl concentration was associated with GDM among Chinese pregnant women. Our findings provide evidence that moderately high Tl exposure may be a novel risk factor for pregnant women health.

Association between maternal antimony exposure and risk of gestational diabetes mellitus: A birth cohort study.

BACKGROUND: A small number of epidemiological studies have suggested the association of antimony (Sb) exposure with type 2 diabetes risk. However, little is known about the relationship between Sb exposure during pregnancy and risk of gestational diabetes mellitus (GDM). OBJECTIVES: To investigate the associations of urinary Sb concentrations with GDM risk and blood glucose levels in pregnant women. METHODS: We analyzed the baseline data of 1789 pregnant women enrolled in the Birth Cohort Study on Prenatal Environments and Offspring Health (PEOH) in Guangzhou, China. Sb concentrations in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and analysis of covariance were used to evaluate associations of Sb exposure with GDM risk and blood glucose levels. RESULTS: A total of 437 (24.4%) women were diagnosed with GDM. The relative risk of GDM for women in the highest quartile of creatinine-corrected Sb (CC-Sb) concentrations was 1.55 [RR (95% CI) = 1.55 (1.12, 2.15), p-trend = 0.005], compared with women in the lowest quartile. Moreover, the women in the top quartile of CC-Sb levels had a 5.2% higher 1 h blood glucose and a 4.2% higher 2 h blood glucose than those in the bottom quartile. We also found an interactive effect between maternal age and CC-Sb on the risk of GDM (p-interaction < 0.001). CONCLUSION: This study suggested significant positive associations of Sb exposure with increased GDM risk and impaired blood glucose homeostasis in pregnant women, and the Sb-GDM association might be modified by maternal age.

Indwelling Intrauterine Foley Balloon Catheter for Intraoperative and Postoperative Bleeding in Cesarean Scar Pregnancy.

STUDY OBJECTIVE: Cesarean scar pregnancy (CSP) is a rare type of ectopic pregnancy, and a significant concern in the management of this condition is the control and prevention of bleeding. We aimed to determine the efficacy and value of an indwelling, intrauterine Foley balloon catheter in controlling and preventing intraoperative and postoperative bleeding in patients with CSP. DESIGN: Retrospective case series. SETTING: University-affiliated hospital. PATIENTS: Between January 1, 2015 and May 31, 2017, 70 patients presented with CSP. INTERVENTIONS: All patients underwent uterine curettage under hysteroscopic guidance and ultrasound monitoring. Patients were then assigned to 2 groups: the study group, with an indwelling Foley balloon catheter placed in the uterine cavity during surgery and retained for 24 to 48 hours, and the control group, without catheter placement. Data were collected to compare the 2 groups in terms of intraoperative and postoperative complications, surgical time, and status of menstruation resumption. MEASUREMENTS AND MAIN RESULTS: The average daily volume of postoperative blood loss during the first 3 postoperative days in the study group was 23.1 mL compared with 31.5 mL observed in the control group (p = .041). Moreover, the study group had significantly shorter average duration of bleeding (p = .027) and fewer menstruation abnormalities than the control group. Uterine ultrasonography performed after resumption of menstruation showed that none of the enrolled patients had any intrauterine abnormalities. CONCLUSIONS: The use of an indwelling, intrauterine Foley balloon catheter has positive results in the management of CSP.

Circadian misalignment alters insulin sensitivity during the light phase and shifts glucose tolerance rhythms in female mice.

Shift work and jet lag, characterized by circadian misalignment, can disrupt several physiological activities, but whether they affect the rhythm of glucose uptake and insulin sensitivity remain unclear. In the present study, female C57BL/6J mice were maintained for four weeks under the condition of 8-hour phase advance and delay every 3-4 days to mimic shift work. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were performed repeatedly at Zeitgeber time (ZT) 0, ZT6, ZT12, and ZT18. Glucose-stimulated insulin secretion (GSIS) test was performed at ZT6. We found that the average level of daily glucose tolerance did not decrease but the phase of glucose tolerance advanced by 2.27 hours and the amplitude attenuated by 20.4% in shift work mice. At ZT6, IPITT showed blood glucose at 30 min after insulin injection decreased faster in shift work mice (-3.50±0.74mmol/L, -61.58±7.89%) than that in control mice (-2.11±1.10mmol/L, -33.72±17.24%), but IPGTT and GSIS test showed no significant difference between the two groups. Food intake monitor showed that the feeding time of shift work mice continued to advance. Restricting feed to a fixed 12-hour period alleviated the increase of insulin sensitivity induced by shift-work. We also observed that an increase of blood glucose and liver glycogen at ZT0, as well as a phase advance of liver clock genes and some glucose metabolism-related genes such as forkhead box O1 (Foxo1) and peroxisome proliferator activated receptor alpha (Pparα) in shift work mice. Our results showed that light change-simulated shift work altered insulin sensitivity during the light phase and shifted glucose tolerance rhythms in female mice, suggesting a causal association between long-term shift work and type 2 diabetes.

Profile and validation of dysregulated long non­coding RNAs and mRNAs in ovarian cancer.

The dysregulation of long non­coding RNAs (lncRNAs) is associated with cancer development. The present study profiled differentially expressed lncRNAs in ovarian cancer (OC) versus normal ovarian tissues (NT) and investigated their potential functions in gene expression. OC tissues from 30 patients and NT specimens from 20 non­tumor patients were collected, and 5 cases of tumor and NT were subjected to lncRNA and mRNA microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to verify microarray data in all 30 cases. There were 2,870 differentially expressed lncRNAs (795 upregulated and 2,075 downregulated) and 2,658 differentially expressed mRNAs (1,014 upregulated and 1,644 downregulated) in OC. A total of 4 upregulated and 4 downregulated lncRNAs were validated using RT­qPCR. The data demonstrated that, with the exception of ENST00000453838 and ENST00000505048, the lncRNAs were consistent with the microarray data. Another differentially expressed lncRNA (BC041954) was assessed using independent tissue samples, and results further supported the microarray data. Moreover, GO analysis showed that the upregulated genes were involved in the 'development of the cell anatomical structure' (GO: 0048856; P=5.46x10­6), 'embryo and system development' and 'multicellular organismal development' in biological processes. By contrast, the downregulated genes were involved in 'gene expression' (GO: 0010476; P=1.81x10­6), 'nitrogen compound metabolic process', 'kidney development' and the 'cellular nitrogen compound metabolic process'. These differentially expressed lncRNAs could be classified into four classes, namely, the enhancer lncRNA nearby coding gene, HOX cluster, long­intergenic non­coding RNAs (lincRNAs) nearby coding gene and Rinn lincRNAs. Coding­non­coding gene co­expression network analysis showed the interregulation of lncRNAs and mRNAs in OC development. In conclusion, dysregulated lncRNA and mRNA expression could promote OC development. Further study may validate a number as OC markers and provide novel insights into ovarian cancer biology.

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis through the Cascade Pathway of MEKK2-p38 MAPK-IRF-1-TRADD-Caspase 8 in Rat Thy-1 Nephritis.

The apoptosis of glomerular mesangial cells (GMCs) in the early phase of rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis (MsPGN), is primarily triggered by sublytic C5b-9. However, the mechanism of GMC apoptosis induced by sublytic C5b-9 remains unclear. In this study, we demonstrate that expressions of TNFR1-associated death domain-containing protein (TRADD) and IFN regulatory factor-1 (IRF-1) were simultaneously upregulated in the renal tissue of Thy-1N rats (in vivo) and in GMCs under sublytic C5b-9 stimulation (in vitro). In vitro, TRADD was confirmed to be a downstream gene of IRF-1, because IRF-1 could bind to TRADD gene promoter to promote its transcription, leading to caspase 8 activation and GMC apoptosis. Increased phosphorylation of p38 MAPK was verified to contribute to IRF-1 and TRADD production and caspase 8 activation, as well as to GMC apoptosis induced by sublytic C5b-9. Furthermore, phosphorylation of MEK kinase 2 (MEKK2) mediated p38 MAPK activation. More importantly, three sites (Ser153/164/239) of MEKK2 phosphorylation were identified and demonstrated to be necessary for p38 MAPK activation. In addition, silencing of renal MEKK2, IRF-1, and TRADD genes or inhibition of p38 MAPK activation in vivo had obvious inhibitory effects on GMC apoptosis, secondary proliferation, and urinary protein secretion in rats with Thy-1N. Collectively, these findings indicate that the cascade axis of MEKK2-p38 MAPK-IRF-1-TRADD-caspase 8 may play an important role in GMC apoptosis following exposure to sublytic C5b-9 in rat Thy-1N.

Sublytic C5b-9 triggers glomerular mesangial cell apoptosis in rat Thy-1 nephritis via Gadd45 activation mediated by Egr-1 and p300-dependent ATF3 acetylation.

The apoptosis of glomerular mesangial cells (GMCs) is considered to be an important contributor to the initiation and development of rat Thy-1 nephritis (Thy-1N) and is accompanied by sublytic C5b-9 deposition. However, the mechanism by which sublytic C5b-9 triggers GMC apoptosis has not been elucidated. In this study, functional and histological examinations were performed on GMCs treated with sublytic C5b-9 (in vitro) and renal tissues of Thy-1N rats (in vivo). The in vitro studies found that sublytic C5b-9 could trigger GMC apoptosis through upregulating Egr-1, ATF3, and Gadd45 expression. Egr-1-mediated post-transcriptional modulation of ATF3, Egr-1/ATF3-enhanced Gadd45 promoter activity, and p300-mediated ATF3 acetylation were all involved in GMC apoptosis. More importantly, the effective binding elements for Egr-1 and ATF3 to Gadd45ß/γ promoters and the ATF3 acetylation site were identified. In vivo, silencing renal p300, Egr-1, ATF3, and Gadd45ß/γ significantly decreased GMC apoptosis, secondary GMC proliferation, and urinary protein secretion in Thy-1N rats. Together, these findings implicate that sublytic C5b-9-induced activation of Egr-1/p300-ATF3/Gadd45 axis plays a critical role in GMC apoptosis in Thy-1N rats.