Epstein-Barr virus-encoded BART9 and BART15 miRNAs are elevated in exosomes of cerebrospinal fluid from relapsing-remitting multiple sclerosis patients.

Epstein-Barr virus (EBV) infection is approved as the main environmental trigger of multiple sclerosis (MS). In this path, we quantified ebv-miR-BART9-3p and ebv-miR-BART15 in exosomes of cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients in comparison with the control group. Interestingly, patients displayed significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) expression in CSF exosomes. Moreover, the expression levels of hsa-miR-21-5p and hsa-miR-146a-5p were found to be significantly elevated in the CSF samples obtained from the patient group compared to those obtained from the HC group. The levels of Interferon-gamma (IFN-γ), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-ß), and tumor necrosis factor-alpha (TNF-α) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-ß (8.5-fold), followed by IL-23 (3.9-fold) in CSF exosomes. These findings are in agreement with the association between EBV infection and inflammatory cytokines induction. Furthermore, the ratios of TGF-ß: TNF-α and TGF-ß: IFN-γ attained values of 4 to 16.4 and 1.3 to 3.6, respectively, in the CSF exosomes of the patients, in comparison to those of the control group. These findings show EBV activity in RRMS patients is different from that of healthy ones. Elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines expression in CSF exosomes in RRMS patients provides a substantial link between EBV activity and the onset of the disease, as well as the transition from EBV infection to MS.

Exosome Content-Mediated Signaling Pathways in Multiple Sclerosis.

Exosomes are small extracellular vesicles with a complex lipid-bilayer surface and 30-150 nm diameter. These vesicles play a critical role in intercellular signaling networks during physiopathological processes through data trafficking and cell reprogramming. It has been demonstrated that exosomes are involved in a variety of central nervous system (CNS) disorders such as multiple sclerosis (MS). Exosome mediators' cell-to-cell communication is possibly by delivering their contents such as proteins, RNAs (coding and non-coding), DNAs (mitochondrial and genomic), and transposable elements to the target cells. Exosomal microRNAs (miRNAs) differ in their expression patterns in MS disease, thereby providing novel diagnostic and prognostic biomarkers and therapeutic options for better treatment of MS disease. Furthermore, these microvesicles are non-immunogenic and non-toxic therapeutic tools for transferring miRNAs across the blood-brain barrier (BBB). Collectively, exosomes could be used as novel drug delivery devices for the treatment of MS patients. This review summarized research regarding the exosomes from serum, plasma, PBMC, and other cells in MS patients and experimental models. We also provide a critical view of exosome content-mediated signaling pathways in MS, including TNF-α, TGF-ß, NF-κB, and Wnt pathways. The use of exosomes as a therapeutic potential in MS has also been discussed.

The effect of nanoparticle coating on biological, chemical and biophysical parameters influencing radiosensitization in nanoparticle-aided radiation therapy.

Nanoparticle-based composites have the potential to meet requirements for radiosensitization in both therapeutic and diagnostic applications. The radiosensitizing properties of nanoparticles could be reliant on the nature of their coating layer. Any gains in reduced toxicity and aggregation or improved delivery to tumor cells for coated nanoparticles must be weighed against the loss of dose enhancement. The radiosensitization potential of coated NPs is confirmed by numerous studies but in most of them, the coating layer is mostly applied to reduce toxicity of the NPs and for stability and biocompatibility aims. While the direct effects of the coating layer in radiosensitization-were ignored and not considered. This review provides an overview of double-edged impact of nanoparticle coating on the radiosensitization potential of nanostructures and discusses the challenges in choosing appropriate coating material in the aim of achieving improved radioenhancement. Coating layer could affect the radiosensitization processes and thereby the biological outcomes of nanoparticle-based radiation therapy. The physicochemical properties of the coating layer can be altered by the type of the coating material and its thickness. Under low-energy photon irradiation, the coating layer could act as a shield for nanoparticles capable of absorb produced low-energy electrons which are important levers for local and nanoscopic dose enhancement. Also, it seems that the coating layer could mostly affect the chemical process of ROS production rather than the physicochemical process. Based on the reviewed literature, for the irradiated coated nanoparticles, the cell survival and viability of cancer cells are decreased more than normal cells. Also, cell cycle arrest, inhibition of cell proliferation, DNA damage, cell death and apoptosis were shown to be affected by coated metallic nanoparticles under irradiation.

Effects of 14-days bismuth- and tetracycline-containing quadruple therapy with concomitant regimen for the first line Helicobacterpylori eradication.

Background: Helicobacter pylori (H. pylori) has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma. Methods: This study was performed in Mazandaran, Sari, situated in North of Iran. Three-hundred and twenty-eight adult patients with endoscopically approved gastric or duodenal ulcers or erosions and H. pylori infection were randomly divided into 2 groups to receive either 14 days PABT (Pantoprazole 40 mg, Amoxicillin 1 g, Bismuth 425 mg (all twice daily) and Tetracycline 500 mg four times a day) and PACM (Pantoprazole 40 mg, Amoxicillin 1g, Clarithromycin 500 mg, and Metronidazole 500 mg, all twice daily). To evaluate H. pylori eradication, fecal H. pylori antigen test was performed 8 weeks after treatment. Results: The eradication rates were 94.51% in the PABT and 91.46% in PACM group based on the intention to treat analysis. Moreover, the eradication rates were 95.58% and 92.72% according to per-protocol analysis, respectively. Also, both groups had very low rates of severe side effects. Conclusion: Regarding the ideal eradication rates achieved by both treatment groups and the low rates of severe side effects, both treatment protocols can be prescribed for H. pylori eradication in North of Iran.

Non-inferiority of reverse hybrid regimen versus standard concomitant regimen for H. pylori eradication in a randomized-controlled trial.

Background: Helicobacter pylori (H. pylori) infection is strongly related to peptic ulcer disease, chronic gastritis, and gastric malignancies. Therefore, H. pylori eradication is necessary in these cases. This study was aimed to compare the efficacy of 14-day reverse hybrid therapy with standard 14-day concomitant regimen for H. pylori eradication in Iran. Methods: Of the 317 patients with dyspepsia and H. pylori infection enrolled in the study, 153 and 164 patients were randomly assigned to reverse hybrid and concomitant groups, respectively. The reverse hybrid regimen containing pantoprazole, amoxicillin, clarithromycin, and metronidazole was taken every 12 hours in the first 7 days, however, Clarithromycin and Metronidazole were discontinued within the next 7 days. Patients in the concomitant group also received the same drugs for 14-day. Eradication confirmation tests were used 8 weeks after the end of treatments. Results: A crowd of 281 patients continued the trial until the end. H. pylori eradication rates based on intention to treat analysis were 71.2% (109/153) and 83.5% (137/164) in reverse hybrid and concomitant groups, respectively (P = 0.007). By the per-protocol analysis, rates of eradication were 85.8% (109/127) and 89% (137/154), respectively (P = 0.428). Severe side effects were few in both groups. More side effects were observed in concomitant group (p < 0.001), however, the severity of side effects was not statistically different between the two regimens (P = 0.314). Reverse hybrid regimen was better tolerated (98% vs. 91.5%, P = 0.009). Conclusion: Both 14-day reverse hybrid and concomitant regimens have a fair response rate in Iran.

A snapshot of miRNAs in oral squamous cell carcinoma: Difference between cancer cells and corresponding normal cells.

Oral squamous cell carcinoma (OSCC) constitutes the most aggressive tumors of the oral cavity and is one of the leading causes of cancer mortality worldwide. Although recent clinical treatment strategies have improved the survival rate, the outcome of OSCC patients still remains dismal because of the lack of efficient diagnostic and treatment tools. As one of the main actors of OSCC scenario, microRNAs (miRNAs) are involved in triggering, progression and metastasis through the regulation of various cancer-related signaling pathways. Identification followed by precise study of the biology and mechanism of action of miRNAs will greatly help to provide valuable insights regarding OSCC development and can be considered as an anti-OSCC target. In the current review, we have provided a focused summary of the latest published papers on the role of miRNAs in apoptosis, cell cycle, proliferation, EMT and metastasis of OSCC as well as the role of long noncoding RNAs in the modulation of miRNAs in OSCC.

Enhanced Maturation of 3D Bioprinted Skeletal Muscle Tissue Constructs Encapsulating Soluble Factor-Releasing Microparticles.

Several microfabrication technologies have been used to engineer native-like skeletal muscle tissues. However, the successful development of muscle remains a significant challenge in the tissue engineering field. Muscle tissue engineering aims to combine muscle precursor cells aligned within a highly organized 3D structure and biological factors crucial to support cell differentiation and maturation into functional myotubes and myofibers. In this study, the use of 3D bioprinting is proposed for the fabrication of muscle tissues using gelatin methacryloyl (GelMA) incorporating sustained insulin-like growth factor-1 (IGF-1)-releasing microparticles and myoblast cells. This study hypothesizes that functional and mature myotubes will be obtained more efficiently using a bioink that can release IGF-1 sustainably for in vitro muscle engineering. Synthesized microfluidic-assisted polymeric microparticles demonstrate successful adsorption of IGF-1 and sustained release of IGF-1 at physiological pH for at least 21 days. Incorporating the IGF-1-releasing microparticles in the GelMA bioink assisted in promoting the alignment of myoblasts and differentiation into myotubes. Furthermore, the myotubes show spontaneous contraction in the muscle constructs bioprinted with IGF-1-releasing bioink. The proposed bioprinting strategy aims to improve the development of new therapies applied to the regeneration and maturation of muscle tissues.

Structure-activity relationship of pyrazol-4-yl-pyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M4) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M4 positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M4 PET ligand that allows the non-invasive visualization of M4 in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [18F]12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/µmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [18F]12 for the M4-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [18F]12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [18F]12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [18F]12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M4 PET radioligand with promising attributes. The availability of a clinically validated M4 PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

Epidemiological, Endoscopic, Clinical, and Pathological Features of Patients with Celiac Diseases in Southern Littoral of Caspian Sea.

Background: Celiac disease is an autoimmune disorder resulting from gluten consumption in genetically predisposed individuals. The present study investigated the epidemiological, endoscopic, and clinicopathological features of patients with celiac disease in the southern littoral of the Caspian Sea. Methods: 140 patients with celiac disease were interviewed and examined regarding demographic characteristics, clinical symptoms, and serologic, endoscopic, and pathological findings. Results: 44 (31.4%) of the patients were male and 68.6% were female. The mean age of the patients at diagnosis was 27.13±13.4 years (ranging from 2 to 60 years). The most common gastrointestinal (GI) symptoms were bloating (47.8%), abdominal pain (47.1%) and diarrhea (30.7%), respectively. Also, 17 (12.1%) patients did not complain of any GI symptoms.18 (12.8%) patients had aphthous stomatitis, 10.7% had dermatitis herpetiformis, 3.6% suffered from itching without a rash, two (1.4%) mentioned psoriasis and one (0.7%) had lichen planus. 19 (19.7%) of the female patients complained of menstrual bleeding disorders, 4% mentioned infertility, and 2% experienced primary amenorrhea. The most common comorbid condition was hypothyroidism in 16 (11.4%) patients. The most common endoscopic finding was duodenal scalloping (37.25%). In addition, 7.8% of the patients had a normal endoscopic appearance. 43 (30.7%) patients were classified as Marsh IIIC, 25.7% Marsh IIIB, 17.8% Marsh IIIA, 12.8% Marsh II and 12.8% were classified as Marsh I. Conclusion: Since celiac disease can present with non-GI manifestations and the majority of our patients had Marsh III classification, it seems that celiac disease must be considered as a routine screening test in GI clinics, and also, it should be kept in mind as a differential diagnosis in other specialty fields.

Endothelial-Smooth Muscle Cell Interactions in a Shear-Exposed Intimal Hyperplasia on-a-Dish Model to Evaluate Therapeutic Strategies.

Intimal hyperplasia (IH) represents a major challenge following cardiovascular interventions. While mechanisms are poorly understood, the inefficient preventive methods incentivize the search for novel therapies. A vessel-on-a-dish platform is presented, consisting of direct-contact cocultures with human primary endothelial cells (ECs) and smooth muscle cells (SMCs) exposed to both laminar pulsatile and disturbed flow on an orbital shaker. With contractile SMCs sitting below a confluent EC layer, a model that successfully replicates the architecture of a quiescent vessel wall is created. In the novel IH model, ECs are seeded on synthetic SMCs at low density, mimicking reendothelization after vascular injury. Over 3 days of coculture, ECs transition from a network conformation to confluent 2D islands, as promoted by pulsatile flow, resulting in a "defected" EC monolayer. In defected regions, SMCs incorporated plasma fibronectin into fibers, increased proliferation, and formed multilayers, similarly to IH in vivo. These phenomena are inhibited under confluent EC layers, supporting therapeutic approaches that focus on endothelial regeneration rather than inhibiting proliferation, as illustrated in a proof-of-concept experiment with Paclitaxel. Thus, this in vitro system offers a new tool to study EC-SMC communication in IH pathophysiology, while providing an easy-to-use translational disease model platform for low-cost and high-content therapeutic development.

Efficacy of 14-day concomitant quadruple therapy and 14-day high-dose dual therapy on H. pylori eradication.

Aim: We compared the efficacy of two different regimens for H. pylori eradication in areas with high antibiotic resistance. Background: Helicobacter pylori (H. pylori) is a gram-negative bacillus that has a strong association with chronic gastritis and peptic ulcer disease. Different regimens with varying degrees of effectiveness have been used for H. pylori eradication. Methods: The current randomized controlled trial (RCT) randomly assigned 217 patients who had indications for H. pylori eradication therapy to two groups. One group were administered concomitant quadruple therapy (pantoprazole 40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) for 14 days, and the second group received 14 days of high-dose dual therapy, consisting of esomeprazole 40 mg BID and amoxicillin 1g TDS. H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rates by PP analysis for 14 days concomitant quadruple therapy and high-dose dual therapy were 88.6% (95% CI, 80.3-92.8) and 82.2% (95% CI, 74.8-89.5), respectively (p = 0.19). According to intention-to-treat (ITT) analysis, the eradication rates were 81.6% (95% CI, 74.5-88.6) and 80.6% (95% CI, 73-88.1), respectively (p = 0.58). Overall drug side effects were 20.8% in high-dose dual therapy and 49.6% in concomitant quadruple therapy (p < 0.001). Conclusion: Fourteen days concomitant quadruple therapy can be considered as a relatively acceptable regimen for H. pylori eradication in areas with high clarithromycin and metronidazole resistance. It seems that high-dose dual therapy could be a promising alternative regimen in these areas.

Fatty acids of type 2 diabetic serum decrease the stemness properties of human adipose-derived mesenchymal stem cells.

In type 2 diabetes, dyslipidemia and increased serum free fatty acids (FFAs) exacerbate the development of the disease through a negative effect on insulin secretion. Adipose-derived mesenchymal stem cells (AdMSCs) play a key role in regenerative medicine, and these cells can potentially be applied as novel therapeutic resources in the treatment of diabetes. In this study, AdMSCs were treated with diabetic or nondiabetic serum FFAs isolated from women of menopausal age. Serum FFAs were analyzed using gas-liquid chromatography. The expression level of the stemness markers CD49e and CD90 and the Wnt signaling target genes Axin-2 and c-Myc were evaluated using real-time PCR. The proliferation rate and colony formation were also assessed using a BrdU assay and crystal violet staining, respectively. The level of glutathione was assessed using cell fluorescence staining. Compared to nondiabetic serum, diabetic serum contained a higher percentage of oleate (1.5-fold, p < 0.01). In comparison with nondiabetic FFAs, diabetic FFAs demonstrated decreasing effects on the expression of CD90 (-51%, p < 0.001) and c-Myc (-48%, p < 0.05), and proliferation rate (-35%, p < 0.001), colony formation capacity (-50%, p < 0.01), and GSH levels (-62%, p < 0.05). The negative effect of the FFAs of diabetic serum on the stemness characteristics may impair the regenerative capabilities of AdMSCs.

The porcupine inhibitor WNT974 provokes ectodermal lineage differentiation of human embryonic stem cells.

Porcupine (Porcn) enzyme plays an essential role in Wnt signaling activation. Stearoyl-CoA desaturase-1 (SCD1) is required to provide Porcn substrates. The aim of this study was to determine the effect of a novel Porcn inhibitor on the fate of human embryonic stem cells (hESCs) and the reliance of Porcn on SCD1 activity. hESCs were cultured on a feeder layer or Matrigel-coated plates. Small molecules WNT974 (LGK-974) and CAY10566 were used to inhibit Porcn and SCD1 activity, respectively. We assessed the effect of Porcn inhibition on viability, expression of Wnt signaling targets, pluripotency markers, proliferation, differentiation, and protein fatty acylation. hESCs' conditioned medium (CM) containing secreted Wnt proteins were applied in rescue experiments. To examine the catalytic dependency of Porcn on SCD1, the results of combined inhibitor treatment were compared with the SCD1 inhibitor alone. LGK-974 at the selected concentrations showed mild effects on hESCs viability, but significantly reduced messenger RNA and protein expression of Wnt signaling targets (Axin-2 and c-Myc) and pluripotency markers (OCT-4 and SOX-2) (p < .05). Adding 1 µM of Porcn inhibitor reduced proliferation (p = .03) and enhanced differentiation capacity into ectodermal progenitors (p = .02), which were reverted by CM. Click chemistry reaction did not show significant alteration in protein fatty acylation upon LGK-974 treatment. Moreover, combined inhibitor treatment caused no further substantial reduction in Wnt signaling targets, pluripotency markers, and protein fatty acylation relative to CAY10566-treated cultures. The substrate availability for Porcn activity is regulated by SCD1 and targeting Porcn by LGK-974 prompts the transition of hESCs from self-renewal state to ectodermal lineage.

A proposed fractional dynamic system and Monte Carlo-based back analysis for simulating the spreading profile of COVID-19.

This paper presents a dynamic system for estimating the spreading profile of COVID-19 in Thailand, taking into account the effects of vaccination and social distancing. For this purpose, a compartmental network is built in which the population is divided into nine mutually exclusive nodes, including susceptible, insusceptible, exposed, infected, vaccinated, recovered, quarantined, hospitalized, and dead. The weight of edges denotes the interaction between the nodes, modeled by a series of conversion rates. Next, the compartmental network and corresponding rates are incorporated into a system of fractional partial differential equations to define the model governing the problem concerned. The fractional degree corresponding to each compartment is considered the node weight in the proposed network. Next, a Monte Carlo-based optimization method is proposed to fit the fractional compartmental network to the actual COVID-19 data of Thailand collected from the World Health Organization. Further, a sensitivity analysis is conducted on the node weights, i.e., fractional orders, to reveal their effect on the accuracy of the fit and model predictions. The results show that the flexibility of the model to adapt to the observed data is markedly improved by lowering the order of the differential equations from unity to a fractional order. The final results show that, assuming the current pandemic situation, the number of infected, recovered, and dead cases in Thailand will, respectively, reach 4300, 4.5 × 10 6 , and 36,000 by the end of 2021.

Advances in microfabrication technologies in tissue engineering and regenerative medicine.

BACKGROUND: Tissue engineering provides various strategies to fabricate an appropriate microenvironment to support the repair and regeneration of lost or damaged tissues. In this matter, several technologies have been implemented to construct close-to-native three-dimensional structures at numerous physiological scales, which are essential to confer the functional characteristics of living tissues. METHODS: In this article, we review a variety of microfabrication technologies that are currently utilized for several tissue engineering applications, such as soft lithography, microneedles, templated and self-assembly of microstructures, microfluidics, fiber spinning, and bioprinting. RESULTS: These technologies have considerably helped us to precisely manipulate cells or cellular constructs for the fabrication of biomimetic tissues and organs. Although currently available tissues still lack some crucial functionalities, including vascular networks, innervation, and lymphatic system, microfabrication strategies are being proposed to overcome these issues. Moreover, the microfabrication techniques that have progressed to the preclinical stage are also discussed. CONCLUSIONS: This article aims to highlight the advantages and drawbacks of each technique and areas of further research for a more comprehensive and evolving understanding of microfabrication techniques in terms of tissue engineering and regenerative medicine applications.

Cold Climate Impact on Air-Pollution-Related Health Outcomes: A Scoping Review.

In cold temperatures, vehicles idle more, have high cold-start emissions including greenhouse gases, and have less effective exhaust filtration systems, which can cause up to ten-fold more harmful vehicular emissions. Only a few vehicle technologies have been tested for emissions below -7 °C (20 °F). Four-hundred-million people living in cities with sub-zero temperatures may be impacted. We conducted a scoping review to identify the existing knowledge about air-pollution-related health outcomes in a cold climate, and pinpoint any research gaps. Of 1019 papers identified, 76 were selected for review. The papers described short-term health impacts associated with air pollutants. However, most papers removed the possible direct effect of temperature on pollution and health by adjusting for temperature. Only eight papers formally explored the modifying effect of temperatures. Five studies identified how extreme cold and warm temperatures aggravated mortality/morbidity associated with ozone, particles, and carbon-monoxide. The other three found no health associations with tested pollutants and temperature. Additionally, in most papers, emissions could not be attributed solely to traffic. In conclusion, evidence on the relationship between cold temperatures, traffic-related pollution, and related health outcomes is lacking. Therefore, targeted research is required to guide vehicle regulations, assess extreme weather-related risks in the context of climate change, and inform public health interventions.

Engineering solutions for biological studies of flow-exposed endothelial cells on orbital shakers.

Shear stress is extremely important for endothelial cell (EC) function. The popularity of 6-well plates on orbital shakers to impose shear stress on ECs has increased among biologists due to their low cost and simplicity. One characteristic of such a platform is the heterogeneous flow profile within a well. While cells in the periphery are exposed to a laminar and high-velocity pulsatile flow that mimics physiological conditions, the flow in the center is disturbed and imposes low shear stress on the cells, which is characteristic of atheroprone regions. For studies where such heterogeneity is not desired, we present a simple cell-patterning technique to selectively prevent cell growth in the center of the well and facilitate the exclusive collection and analysis of cells in the periphery. This guarantees that cell phenotypes will not be influenced by secreted factors from cells exposed to other shear profiles nor that interesting results are obscured by mixing cells from different regions. We also present a multi-staining platform that compartmentalizes each well into 5 smaller independent regions: four at the periphery and one in the center. This is ideal for studies that aim to grow cells on the whole well surface, for comparison with previous work and minimal interference in the cell culture, but require screening of markers by immunostaining afterwards. It allows to compare different regions of the well, reduces antibody-related costs, and allows the exploration of multiple markers essential for high-content screening of cell response. By increasing the versatility of the 6-well plate on an orbital shaker system, we hope that these two solutions motivate biologists to pursue studies on EC mechanobiology and beyond.

Particulate emissions of real-world light-duty gasoline vehicle fleet in Iran.

Fine particulate matter cause profound adverse health effects in Iran. Road traffic is one of the main sources of particulate matter (PM) in urban areas, and has a large contribution in PM2.5 and organic carbon concentration, in Tehran, Iran. The composition of fine PM vehicle emission is poorly known, so this paper aims to determine the mixed fleet source profile by using the analysed data from the two internal stations and the emission factor for PM light-duty vehicles emission. Tunnels are ideal media for extraction vehicle source profile and emission factor, due to vehicles are the only source of pollutant in the urban tunnels. In this study, PM samples were collected simultaneously in two road tunnel stations and at a background site in Niyayesh tunnel in Tehran, Iran. The tunnel samples show a large contribution for some elements and ions, such as Fe (0.23 µg µg-1 OC), Al (0.02 µg µg-1 OC), Ca (0.055 µg µg-1 OC), SO4 (0.047 µg µg-1 OC), Docosane (0.0017 µg µg-1 OC), Triacontane (0.016 µg µg-1 OC), Anthracenedione (0.0003 µg µg-1 OC) and Benzo-perylene (0.0002 µg µg-1 OC). In overall, on-road gasoline vehicle fleets source profile extracted in this study is similar to composite profiles derived from roadside tunnel measurment performed in other countries during the last decades. The PM2.5 emission factor for Tehran's light-duty vehicle fleet has been extracted 16.23 mg km-1. vehicle-1and 0.09 g kg-1. The profile would be used for Chemical Mass Balance Model studies for Iran and other countries with a similar road traffic fleet mix. Also, it would be very suitable for use in emission inventories improvement. The results of this study can be used for choosing the best management strategies and provide comperhensive insight to fine PM traffic emission in Tehran.