Biomimetic lizard robot for adapting to Martian surface terrain.

The exploration of the planet Mars still is a top priority in planetary science. The Mars surface is extensively covered with soil-like material. Current wheeled rovers on Mars have been occasionally experiencing immobilization instances in unexpectedly weak terrains. The development of Mars rovers adaptable to these terrains is instrumental in improving exploration efficiency. Inspired by locomotion of the desert lizard, this paper illustrates a biomimetic quadruped robot with structures of flexible active spine and toes. By accounting for spine lateral flexion and its coordination with four leg movements, three gaits of tripod, trot and turning are designed. The motions corresponding to the three gaits are conceptually and numerically analyzed. On the granular terrains analog to Martian surface, the gasping forces by the active toes are estimated. Then traversing tests for the robot to move on Martian soil surface analog with the three gaits were investigated. Moreover, the traversing characteristics for Martian rocky and slope surface analog are analyzed. Results show that the robot can traverse Martian soil surface analog with maximum forward speed 28.13 m s-1turning speed 1.94° s-1and obstacle height 74.85 mm. The maximum angle for climbing Martian soil slope analog is 28°, corresponding slippery rate 76.8%. It is predicted that this robot can adapt to Martian granular rough terrain with gentle slopes.

Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/ß-catenin pathway.

As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the ß-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/ß-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/ß-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.

Development of a Lizard-Inspired Robot for Mars Surface Exploration.

Exploring Mars is beneficial to increasing our knowledge, understanding the possibility of ancient microbial life there, and discovering new resources beyond the Earth to prepare for future human missions to Mars. To assist ambitious uncrewed missions to Mars, specific types of planetary rovers have been developed for performing tasks on Mars' surface. Due to the fact that the surface is composed of granular soils and rocks of various sizes, contemporary rovers can have difficulties in moving on soft soils and climbing over rocks. To overcome such difficulties, this research develops a quadruped creeping robot inspired by the locomotion characteristics of the desert lizard. This biomimetic robot features a flexible spine, which allows swinging movements during locomotion. The leg structure utilizes a four-linkage mechanism, which ensures a steady lifting motion. The foot consists of an active ankle and a round pad with four flexible toes that are effective in grasping soils and rocks. To determine robot motions, kinematic models relating to foot, leg, and spine are established. Moreover, the coordinated motions between the trunk spine and leg are numerically verified. In addition, the mobility on granular soils and rocky surface are experimentally demonstrated, which can imply that this biomimetic robot is suitable for Mars surface terrains.

Continuous air purification by aqueous interface filtration and absorption.

The adverse impact of particulate air pollution on human health1,2 has prompted the development of purification systems that filter particulates out of air3-5. To maintain performance, the filter units must inevitably be replaced at some point, which requires maintenance, involves costs and generates solid waste6,7. Here we show that an ion-doped conjugated polymer-coated matrix infiltrated with a selected functional liquid enables efficient, continuous and maintenance-free air purification. As the air to be purified moves through the system in the form of bubbles, the functional fluid provides interfaces for filtration and for removal of particulate matter and pollutant molecules from air. Theoretical modelling and experimental results demonstrate that the system exhibits high efficiency and robustness: its one-time air purification efficiency can reach 99.6%, and its dust-holding capacity can reach 950 g m-2. The system is durable and resistant to fouling and corrosion, and the liquid acting as filter can be reused and adjusted to also enable removal of bacteria or odours. We anticipate that our purification approach will be useful for the development of specialist air purifiers that might prove useful in a settings such as hospitals, factories and mines.

Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study.

BACKGROUND: To date, there is no approved blood-based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. METHODS: We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre-treatment serum SEMA4C levels, measured using optimized in-house enzyme-linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. RESULTS: We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900-0.941) and 0.932 (95%CI: 0.911-0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early-stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916-0.946) and 0.879 (95%CI: 0.832-0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. CONCLUSIONS: Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

Cow dung-derived biochars engineered as antibacterial agents for bacterial decontamination.

Disposal of the pollutants arising from farming cattle and other livestock threatens the environment and public safety in diverse ways. Herein, we report on the synthesis of engineered biochars using cow dung as raw material, and investigating these biochars as antibacterial agents for water decontamination. By coating the biochars with N-halamine polymer and loading them with active chlorine (i.e., Cl+), we were able to regulate them on demand by tuning the polymer coating and bleaching conditions. The obtained N-halamine-modified biochars were found to be extremely potent against Escherichia coli and Staphylococcus aureus. We also investigated the possibility of using these N-halamine-modified biochars for bacterial decontamination in real-world applications. Our findings indicated that a homemade filter column packed with N-halamine-modified biochars removed pathogenic bacteria from mining sewage, dairy sewage, domestic sewage, and artificial seawater. This proposed strategy could indicate a new way for utilizing livestock pollutants to create on-demand decontaminants.

The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening.

AIM: We aimed to explore the application of PAX1 methylation and human papillomavirus (HPV) E6/E7 mRNA detection in cervical cancer screening and to compare the efficacy with high-risk (HR)-HPV detection. PATIENTS AND METHODS: The cervical exfoliative cytology samples of 337 patients were collected, including 70 cases of cervical inflammation, 72 cases of low-grade squamous intraepithelial lesions, 97 cases of high-grade squamous intraepithelial lesions, and 98 cases of cervical carcinoma. The PAX1 gene methylation (PAX1) status was detected by multiple quantitative PCR, HPV E6/E7 mRNA (E6/E7) was detected by QuantiVirus detection, and HR-HPV (HPV) was detected by the Cobas 4800 detection system. The sensitivities, specificities, and accuracies were validated in the testing set. RESULTS: The sensitivities of the HPV, HPV E6/E7, and PAX1 testing were 89.23%, 84.10%, and 86.67%, respectively, which all maintained a high level. In contrast, the specificities of the HPV, E6/E7, and PAX1 testing were only 19.10%, 37.32%, and 97.18% (in pairwise comparisons, p = 0.000). The AUC of PAX1 (0.919) was significantly larger than that of HPV (0.541) and E6/E7 detection (0.607) (p < 0.0001). In addition, the AUC areas of all combined parallel testing were lower than that of single PAX1 test (p < 0.05). CONCLUSION: The diagnostic efficacy of E6/E7 detection and PAX1 detection was better than that of HPV detection, especially for PAX1 detection.

Bisphosphine-Stabilized Gold Nanoclusters with the Crown/Birdcage-Shaped Au11 Cores: Structures and Optical Properties.

To estimate the effect of bisphosphine ligands on the formation of the isomeric core structures of gold nanoclusters, the different ligation of bisphosphine ligands is usually used to participate in the construction of gold nanoclusters. Here, the selection of the different bisphosphine ligands, DPEphos and Xantphos, is performed to construct two novel gold nanoclusters, [Au11(DPEphos)4Cl2]Cl (1) and [Au11(Xantphos)4Cl2]Cl(2), which have been characterized by IR, 1H and 31P NMR, ESI-MS, XRD, SEM, XPS, TG, UV-vis, and X-ray crystal structure analysis. The structural analyses indicate that the ligation of bisphosphine ligands play a crucial role in the formation of the fascinating Au11 cores: gold nanocluster 1 includes a birdcage-shaped Au11 core with eight electrons, while gold nanocluster 2 contains a crown-shaped Au11 core with eight electrons. Meanwhile, DOS and PDOS studies indicate that the Au11 cores have a strong effect on the composition of HOMO and LUMO orbitals of gold nanoclusters. Furthermore, the different Au11 core structures lead to different optical absorption characteristics (1: 456 nm; 2: 427 nm). All these demonstrate that the ligation of bisphosphine ligands may have an important influence on constructing the stability of the isomeric core structures of gold nanoclusters.

Molecular method for rapid detection of the red tide dinoflagellate Karenia mikimotoi in the coastal region of Xiangshan Bay, China.

The species Karenia mikimotoi is a common nearshore red tide alga that can secrete hemolytic exotoxin and ichthyotoxin, which can induce the death of fish and shellfish, causing severe economic losses. In this study, loop-mediated isothermal amplification (LAMP) was employed in combination with the lateral flow dipstick (LFD) visual detection method to establish the LAMP-LFD rapid detection method for K. mikimotoi. The internal transcribed spacer ITS1-5.8S-ITS2 of K. mikimotoi was used as the target sequence and was amplified with specific primers designed in this study. The results indicated that the amplification optimal reaction conditions for LAMP in this paper were for 20 min at 65 °C. Moreover, LAMP had excellent specificity, showing negative results for other common red tide causing algal species. In field samples, we successfully reduced the total time, with only 23 min needed from LAMP amplification to LFD result display, which was shorter than that of conventional PCR. Consequently, LAMP-LFD should be useful for rapid field detection of low-density K. mikimotoi and for the early prevention of red tide induced by such algae.

Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer.

Semaphorins are a large family of evolutionarily conserved morphogenetic molecules that are associated with repelling axonal guidance. Intriguingly, recent researches indicate that semaphorins are involved in cancer progression. Semaphorin 4C (SEMA4C) has long been considered a neuronal migration gene, but we detected that it is also highly expressed in many malignant human cancers. During an investigation of subcutaneous tumor models, we found that SEMA4C expression promoted tumor growth and progression. We discovered that SEMA4C was involved in maintaining tumor cell self-renewal, likely by regulating the p53 pathway. Inhibiting the expression of endogenous SEMA4C in tumor cells impaired growth and induced senescence and cell-cycle arrest in the G2-phase. In addition, we found that SEMA4C induced the production of angiogenin and colony-stimulating factor-1 (CSF-1) in tumor cells by activating the NF-κB pathway in a plexinB2-dependent manner. In conclusion, SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis. Thus, inhibition of SEMA4C activity may be a novel therapeutic strategy for human breast cancer. IMPLICATIONS: In breast cancer, therapeutic targeting of the SEMA4C pathway may prevent tumor growth, angiogenesis, metastasis, and progression.

[A novel mutation in the ETFDH gene of an infant with multiple acyl-CoA dehydrogenase deficiency].

This article reports the results of tandem mass spectrometry and the mutation features of the ETFDH gene for an infant with multiple acyl-CoA dehydrogenase deficiency. The results of tandem mass spectrometry showed that C14 : 1, C8, C6, C10, and C12 increased. Exon sequencing was performed on this infant and his parents and revealed double heterozygous mutations in the ETFDH gene of the infant: c.992A>T and c.1450T>C. The former was inherited from his mother, and the latter was inherited from his father. c.1450T>C was shown to be the pathogenic mutation in the HGMD database. PolyPhen2, SIFT, and PROVEAN all predicted that the novel mutation c.992A>T might be pathogenic, and the mutant amino acids were highly conserved across various species. The findings expand the mutation spectrum of the ETFDH gene, and provide molecular evidence for the etiological diagnosis of the patient with multiple acyl-CoA dehydrogenase deficiency as well as for the genetic counseling and prenatal diagnosis in the family.

Smad4 deletion in blood vessel endothelial cells promotes ovarian cancer metastasis.

SMAD4 is a critical co-smad in signal transduction pathways activated in response to transforming growth factor-ß (TGF-ß)-related ligands, regulating cell growth and differentiation. The roles played by SMAD4 inactivation in tumors highlighted it as a tumor-suppressor gene. Herein, we report that loss of SMAD4 expression in vascular endothelial cells promotes ovarian cancer invasion. SiRNA transfer of this gene in the HUVEC reduced SMAD4 protein expression and function. Although it reduced the vessel endothelial cell tubule formation in vitro and in vivo, it did not affect the tumor growth significantly in vivo. However, it weakened the barrier integrity in endothelial cells and increased vessel permeability and the ovarian cancer liver metastasis. We documented reduced angiogenesis and increased invasion histologically and by intravital microscopy, and gained mechanistic insight at the messenger and gene level. Finally, we found a negative reciprocal regulation between SMAD4 and FYN. FYN is one of the Src family kinases (SFK), activation of which can cause dissociation of cell-cell junctions and adhesion, resulting in paracellular hypermeability. Upon SMAD4 deletion, we detected high expression levels of FYN in vessel endothelial cells, suggesting the mechanism of the ovarian tumor cells cross the endothelial barrier and transform to an invasive phenotype.

The role of the ATM/Chk/P53 pathway in mediating DNA damage in hand-foot syndrome induced by PLD.

Pegylated liposomal doxorubicin (PLD) has been approved to treat patients with various types of cancers because it rarely caused side effects, such as cardiotoxicity, in comparison to doxorubicin, but it frequently results in hand-foot syndrome (HFS). This may affect the quality of life and require a reduction in the PLD dose. The pathophysiology of HFS was not well understood. This study was aimed at exploring the mechanism of HFS induced by PLD. We compared the effects of different doses of PLD on the proliferation inhibition and apoptosis in vitro in HaCaT cells and analyzed the skin changes and skin cell DNA damage in vivo using a zebrafish model. The results suggested that very low doses of PLD show a proliferation inhibition (cell cycle arrest at G2/M phase) and an apoptosis phenotype characterized by the ATM/Chk/P53 pathway that mediates DNA damage in vitro in HaCaT cells. In addition, PLD enhanced zebrafish skin pigmentation from the head to the trunk and induced DNA damage (phospho-H2AX staining) and cell death in the skin of zebrafish. The results of the present study suggested potential applications to provide a better understanding of the apoptosis of PLD-treated skin cells and described a simple methodology for detecting a PLD-induced DNA damage response in zebrafish, which may be helpful in preventing and treating HFS.

Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C.

PURPOSE: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis. EXPERIMENTAL DESIGN: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs. RESULTS: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane-bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2-MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells. CONCLUSIONS: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214-24. ©2016 AACR.

Smad4 is required for the development of cardiac and skeletal muscle in zebrafish.

Transforming growth factor-beta (TGF-beta) regulates cellular functions and plays key roles in development and carcinogenesis. Smad4 is the central intracellular mediator of TGF-beta signaling and plays crucial roles in tissue regeneration, cell differentiation, embryonic development, regulation of the immune system and tumor progression. To clarify the role of smad4 in development, we examined both the pattern of smad4 expression in zebrafish embryos and the effect of smad4 suppression on embryonic development using smad4-specific antisense morpholino-oligonucleotides. We show that smad4 is expressed in zebrafish embryos at all developmental stages examined and that embryonic knockdown of smad4 results in pericardial edema, decreased heartbeat and defects in the trunk structure. Additionally, these phenotypes were associated with abnormal expression of the two heart-chamber markers, cmlc2 and vmhc, as well as abnormal expression of three makers of myogenic terminal differentiation, mylz2, smyhc1 and mck. Furthermore, a notable increase in apoptosis was apparent in the smad4 knockdown embryos, while no obvious reduction in cell proliferation was observed. Collectively, these data suggest that smad4 plays an important role in heart and skeletal muscle development.

ATP1B3: a virus-induced host factor against EV71 replication by up-regulating the production of type-I interferons.

Enterovirus 71 (EV71) infection can cause severe diseases, and is becoming increasingly common in children. In the current study, we carried out yeast two-hybrid assays to screen human proteins that could interact with 3A protein of EV71. Human ß3 subunit of Na(+)/K(+)-ATPase (ATP1B3) protein was demonstrated to interact with the 3A protein of EV71. Although 3A protein had no effect on the expression of ATP1B3, EV71 infection resulted in elevated expression of ATP1B3 in RD cell line, both on messenger RNA (mRNA) and protein levels. Interestingly, knockdown of ATP1B3 could significantly increase the replication of EV71, whereas overexpression of ATP1B3 significantly suppressed the replication of EV71 in RD cells. Furthermore, we demonstrated that the expression of ATP1B3 could induce the production of type-I interferons. Our study demonstrated that ATP1B3 inhibit EV71 replication by enhancing the production of type-I interferons, which could act as a potential therapeutic target in EV71 infection.

Prospective cohort study to evaluate the efficacy of taxane plus platinum and CPT-11plus platinum regimes and to identify prognostic risk factors in cervical cancer patients.

OBJECTIVE: This study was designed to evaluate the response, toxicity and survival of taxanes plus platinum (TP) and CPT-11plus platinum (CP) as neoadjuvant chemotherapies with previously untreated cervical cancer, and to identify prognostic risk factors in these patients. METHODS: A cohort study was performed to evaluate the result of TP and CP regimes in the treatment of cervical cancer patients. RESULTS: The study included 567 patients with locally advanced cervical cancer (LACC) staged as FIGO IB-IIB in our clinical departments. Clinical response was found in 76.1% and 78% of patients in the TP and CP arms, respectively, and no treatment-related deaths were reported. During the follow-up period, disease-free survival (DFS) and overall survival (OS) for the TP and CP arms were not different (P = 0.384 for DFS, P = 0.800 for OS). The CP regime showed higher survival rate for endophytic growth style (P = 0.013 for DFS, P = 0.027 for OS). The CP regime also showed higher DFS and OS for G2 tumor (P = 0.027 for DFS, P = 0.032 for OS). In multivariate cox's proportional hazards regression model, the average death rates were much greater in the non-responder group (HR, 2.68), in the older (> 44 years) group (HR, 2.51), and in the FIGO stage II b patients (HR, 2.84). CONCLUSIONS: The CP regime showed higher survival rate for endophytic growth style or G2 tumor. Clinical response, age and FIGO stage were independent prognostic risk factors in this study for both DFS and OS.

Effect of BRCA2 mutation on familial breast cancer survival: A systematic review and meta-analysis.

Reports of BRCA2 genetic mutations on the prognosis of familial breast cancer (BC) patients have been contradictory. True difference in survival, if it exists, would have important implications for genetic counseling and in treatment of hereditary BC. The purpose of this study was to compare overall survival rate (OSR) among BRCA2 mutation carriers, non-carriers and sporadic BC patients. We searched the PUBMED and EMBASE databases and retrieved 4529 articles using keywords that included breast cancer, BRCA, prognosis and survival. Nine articles were selected for systematic review and among them 6 were included in our meta-analysis. We used the fixed and random effect models to calculate the summary odds ratio (OR) and corresponding 95% confidence interval (CI). BRCA2 mutation carriers had significantly higher long-term OSR than non-carriers (OR=0.69 [95% CI=0.5-0.95]), while both short-term and long-term OSR of BRCA2 mutation carriers did not differ from those of patients with sporadic disease (OR=1.11 [95% CI=0.74-1.65]; 0.85 [95% CI=0.38-1.94], respectively). For BC-specific survival rate (BCSSR), BRCA2 mutation carriers had a similar BCSSR to the non-carriers (OR=0.61 [95% CI=0.28-1.34]). There was no significant difference in disease-free survival (DFS) between BRCA2 mutation carriers and patients with sporadic disease. Our results suggest that BRCA2 mutation increases long-term OSR in hereditary BC, which reminds us a new prospect of management of the disease.

GGPPS, a new EGR-1 target gene, reactivates ERK 1/2 signaling through increasing Ras prenylation.

Cigarette smoke activates the extracellular signal-regulated kinase (ERK) 1/2 mitogen activated-protein kinase pathway, which, in turn, is responsible for early growth response gene-1 (EGR-1) activation. Here we provide evidence that EGR-1 activation can also reactivate ERK 1/2 mitogen activated-protein kinase through a positive feedback loop through its target gene (geranylgeranyl diphosphate synthase) GGPPS. For the first time, the GGPPS gene is identified as a target of EGR-1, as EGR-1 can directly bind to the predicted consensus-binding site in the GGPPS promoter and regulate its transcription. Long-term observations show that there are two ERK 1/2 phosphorylation peaks after cigarette smoke extract stimulation in human lung epithelial Beas-2B cells. The first peak (at 10 minutes) is responsible for EGR-1 accumulation, and the second (at 4 hours) is diminished after the disruption of EGR-1 transcriptional activity. EGR-1 overexpression enhances Ras prenylation and membrane association in a GGPPS-dependent manner, and it augments ERK 1/2 activation. Likewise, a great reduction of the second peak of ERK 1/2 phosphorylation is observed during long-term cigarette smoke extract stimulation in cells where GGPPS is disrupted. Thus, we have uncovered an intricate positive feedback loop in which ERK 1/2-activated EGR-1 promotes ERK 1/2 reactivation through promoting GGPPS transcription, which might affect cigarette smoke-related lung pathological processes.