LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin.

RATIONALE: Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long noncoding RNAs was identified to produce functional polypeptides. However, the functional impact and regulatory mechanisms of long noncoding RNAs in VSMCs phenotype switching remain to be fully elucidated. OBJECTIVES: To illustrate the biological function and mechanism of a VSMC-enriched long noncoding RNA and its encoded peptide in VSMC phenotype switching and vascular remodeling. RESULTS: We identified a VSMC-enriched transcript encoded by a previously uncharacterized gene, which we called phenotype switching regulator (PSR), which was markedly upregulated during vascular remodeling. Although PSR was annotated as a long noncoding RNA, we demonstrated that the lncPSR (PSR transcript) also encoded a protein, which we named arteridin. In VSMCs, both arteridin and lncPSR were necessary and sufficient to induce phenotype switching. Mechanistically, arteridin and lncPSR regulate downstream genes by directly interacting with a transcription factor YBX1 (Y-box binding protein 1) and modulating its nuclear translocation and chromatin targeting. Intriguingly, the PSR transcription was also robustly induced by arteridin. More importantly, the loss of PSR gene or arteridin protein significantly attenuated the vascular remodeling induced by carotid arterial injury. In addition, VSMC-specific inhibition of lncPSR using adeno-associated virus attenuated Ang II (angiotensin II)-induced hypertensive vascular remodeling. CONCLUSIONS: PSR is a VSMC-enriched gene, and its transcript IncPSR and encoded protein (arteridin) coordinately regulate transcriptional reprogramming through a shared interacting partner, YBX1. This is a previously uncharacterized regulatory circuit in VSMC phenotype switching during vascular remodeling, with lncPSR/arteridin as potential therapeutic targets for the treatment of VSMC phenotype switching-related vascular remodeling.

Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis.

Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 µg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 µM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 µM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.

Association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography.

OBJECTIVE: Many previous studies reported the relationship between lipoprotein(a) and cardiovascular disease, but the conclusions were controversial. The aim of our study was to retrospectively investigate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. METHODS: We collected and compared clinical information of patients hospitalized for coronary angiography. Multivariable hierarchical logistic regression was used to evaluate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. RESULTS: There were no significant differences in gender, hypertension, APOA1, smoking, hyperuricemia, obesity, acute myocardial infarction (AMI), cardiac insufficiency, family history of diabetes, or family history of hyperlipidemia among the four groups of lipoprotein(a). Elevated lipoprotein(a) does not increase the risk of hypertriglyceridemia, while elevated lipoprotein(a) increases the risk of high total cholesterol and high low-density lipoprotein cholesterol (LDL-c). Elevated lipoprotein(a) increases the risk of diabetes and premature coronary artery disease (CAD). Elevated lipoprotein(a) increases the incidence of CAD, multivessel lesions, and percutaneous coronary intervention (PCI). Multivariate logistic regression analysis further showed that elevated lipoprotein(a) increases the incidence of high total cholesterol, high LDL­c, diabetes, CAD, premature CAD, multivessel lesions, and PCI. CONCLUSION: The findings indicated that elevated lipoprotein(a) had no obvious relationship with hypertension and obesity. Elevated lipoprotein(a) increases the risk of high total cholesterol, high LDL­c, and premature CAD, and increases the occurrence and severity of coronary heart disease.

The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis.

OBJECTIVE: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment. METHODS: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively. RESULTS: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs). CONCLUSION: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

Prenatal Lipopolysaccharides Exposure Induces Transgenerational Inheritance of Hypertension.

BACKGROUND: Adverse environmental exposure during the prenatal period can lead to diseases in the offspring, including hypertension. Whether or not the hypertensive phenotype can be transgenerationally transmitted is not known. METHODS: Pregnant Sprague Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) on gestation days 6, 8, 10, and 12 to generate the prenatal LPS exposure model. Blood pressure was monitored by both telemetry and tail-cuff method. RNA sequencing was performed to analyze transcriptome alteration in the kidney of the third generation. Tempol and spironolactone were used to test the potential preventative and therapeutic effect of targeting reactive oxygen species and mineralocorticoid receptor signaling, respectively. Molecular biological experiments were performed to illustrate the mechanism of epigenetic and transcription regulation. RESULTS: Prenatal LPS exposure can impair the ability to excrete a salt load and induce hypertension from the first to the third generations, with the fourth and fifth generations, inducing salt-sensitive hypertension. Compared with control pups, the transcriptome in the kidney of the hypertensive third-generation prenatal LPS-exposed offspring have upregulation of the Ras-related C3 botulinum toxin substrate 1 (Rac1) gene and activation of mineralocorticoid receptor signaling. Furthermore, we found that LPS exposure during pregnancy triggered oxidative stress that upregulated KDM3B (histone lysine demethylase 3B) in the oocytes of first-generation female rats, leading to an inheritable low level of H3K9me2 (histone H3 lysine 9 dimethylation), resulting in the transgenerational upregulation of Rac1. Based on these findings, we treated the LPS-exposed pregnant rats with the reactive oxygen species scavenger, tempol, which successfully prevented hypertension in the first-generation offspring and the transgenerational inheritance of hypertension. CONCLUSIONS: These findings show that adverse prenatal exposure induces transgenerational hypertension through an epigenetic-regulated mechanism and identify potentially preventive and therapeutic strategies for hypertension.

Hierarchical Nanoarchitectonics of Ultrathin 2D Organic Nanosheets for Aqueous Processed Electroluminescent Devices.

Ultrathin 2D organic nanosheets (2DONs) with high mobility have received tremendous attention due to thickness of few molecular layers. However, ultrathin 2DONs with high luminescence efficiency and flexibility simultaneously are rarely reported. Here, the ultrathin 2DONs (thickness: 19 nm) through the modulation of tighter molecular packing (distance: ≈3.31 Å) achievable from the incorporation of methoxyl and dipenylamine (DPA) groups into 3D spirofluorenexanthene (SFX) building blocks is successfully prepared. Even with closer molecular stacking, ultrathin 2DONs still enable the suppression of aggregation quenching to exhibit higher quantum yields of blue emission (ΦF  = 48%) than that on amorphous film (ΦF  = 20%), and show amplified spontaneous emission (ASE) with a mediate threshold (332 mW cm-2 ). Further, through drop-casting method, the ultrathin 2DONs are self-organized into large-scale flexible 2DONs films (1.5 × 1.5 cm) with the low hardness (H: 0.008 Gpa) and low Young's modulus (Er : 0.63 Gpa). Impressively, the large-scale 2DONs film can realize electroluminescence performances with a maximum luminance (445 cd m-2 ) and low turn on voltage (3.7 V). These ultrathin 2DONs provide a new avenue for the realization of flexible electrically pumping lasers and intelligent quantum tunneling systems.

Effect of GRK4 on renal gastrin receptor regulation in hypertension.

OBJECTIVE: To investigate whether GRK4 regulates the phosphorylation and function of renal CCKBR. METHODS: GRK4 A142V transgenic mice were used as an animal model of enhanced GRK4 activity, and siRNA was used to silence the GRK4 gene to investigate the regulatory effect of GRK4 on CCKBR phosphorylation and function. Finally, the co-localization and co-connection of GRK4 and CCKBR in RPT cells were observed by laser confocal microscopy and immunoprecipitation to explore the mechanism of GRK4 regulating CCKBR. RESULTS: Gastrin infusion significantly increased urinary flow and sodium excretion rates in GRK4 WT mice (P < .05). GRK4 siRNA did not affect CCKBR protein expression in WKY RPT cells and SHR RPT cells, but remarkably reduced CCKBR phosphorylation in WKY and SHR RPT cells (P < .05). The inhibitory effect of gastrin on Na+-K+ -ATPase activity in WKY RPT cells was further enhanced by the reduction of GRK4 expression (P < .05), while GRK4 siRNA restored the inhibitory effect of gastrin on Na+-K+ -ATPase activity in SHR RPT cells. Laser confocal and Co-immunoprecipitation results showed that GRK4 and CCKBR co-localized in cultured RPT cells' cytoplasm. CONCLUSION: GRK4 participates in the development of hypertension by regulating the phosphorylation of renal CCKBR leading to impaired CCKBR function and water and sodium retention. Knockdown of GRK4 restored the function of CCKBR. The enhanced co-connection between GRK4 and CCKBR may be an important reason for the hyperphosphorylation of GRK4 and CCKBR involved in the pathogenesis of hypertension.

G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation.

Activation of the angiotensin II type 2 receptor (AT2R) induces diuresis and natriuresis. Increased expression or/and activity of G-protein-coupled receptor kinase 4 (GRK4) or genetic variants (e.g., GRK4γ142V) cause sodium retention and hypertension. Whether GRK4 plays a role in the regulation of AT2R in the kidney remains unknown. In the present study, we found that spontaneously hypertensive rats (SHRs) had increased AT2R phosphorylation and impaired AT2R-mediated diuretic and natriuretic effects, as compared with normotensive Wistar-Kyoto (WKY) rats. The regulation by GRK4 of renal AT2R phosphorylation and function was studied in human (h) GRK4γ transgenic mice. hGRK4γ142V transgenic mice had increased renal AT2R phosphorylation and impaired AT2R-mediated natriuresis, relative to hGRK4γ wild-type (WT) littermates. These were confirmed in vitro; AT2R phosphorylation was increased and AT2R-mediated inhibition of Na+-K+-ATPase activity was decreased in hGRK4γ142V, relative to hGRK4γ WT-transfected renal proximal tubule (RPT) cells. There was a direct physical interaction between renal GRK4 and AT2R that was increased in SHRs, relative to WKY rats. Ultrasound-targeted microbubble destruction of renal GRK4 decreased the renal AT2R phosphorylation and restored the impaired AT2R-mediated diuresis and natriuresis in SHRs. In vitro studies showed that GRK4 siRNA reduced AT2R phosphorylation and reversed the impaired AT2R-mediated inhibition of Na+-K+-ATPase activity in SHR RPT cells. Our present study shows that GRK4, at least in part, impairs renal AT2R-mediated diuresis and natriuresis by increasing its phosphorylation; inhibition of GRK4 expression and/or activity may be a potential strategy to improve the renal function of AT2R.

Neutrophil extracellular traps contribute to tissue plasminogen activator resistance in acute ischemic stroke.

Circulating neutrophil extracellular traps (NETs) resistant to t-PA have not been studied completely although NETs in thrombi may contribute to tissue plasminogen activator (t-PA) resistance. This research intended to elucidate whether circulating NETs are associated with t-PA resistance and the underlying mechanism. The levels of NETs were detected in the circulating neutrophils, ischemic brain tissue of acute ischemic stroke (AIS) patients, and transient middle cerebral artery occlusion (tMCAO) models. NET formation in blood, thrombi, and ischemic brain tissue of mice were analyzed by immunofluorescence. Exposed phosphatidylserine (PS) was assessed using flow cytometry and confocal microscopy. Procoagulant activity (PCA) was evaluated using fibrin formation assays, thrombin, and purified coagulation complex. The plasma levels of NETs in AIS patients were significantly higher than those in healthy individuals. After thrombolysis, a significant increase was noted in NET markers in no-improvement patients, while the changes in improvement patients were not significant. Importantly, NETs were decorated with von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) in the blood and thrombi, which could reverse the fibrinolytic effects. In addition, NETs activated platelets (PLTs) and endothelial cells (ECs), stimulating a procoagulant phenotype and facilitating vWF and PAI-1 release. DNase I, activated protein C (APC), and sivelestat markedly inhibited these effects. Furthermore, targeting NETs protected mice from tMCAO-induced cerebral ischemia, possibly by regulating vWF and PAI-1. In summary, NETs may contribute to t-PA resistance in AIS through activation of PLTs and ECs. Strategies against NETs may present a promising therapeutic approach to improve the thrombolysis efficiency of t-PA in AIS patients.

Arsenic trioxide inhibits angiogenesis of hepatocellular carcinoma after insufficient radiofrequency ablation via blocking paracrine angiopoietin-1 and angiopoietin-2.

OBJECTIVES: Angiogenesis occurs during tumor progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). Arsenic trioxide (ATO) shows promising therapeutic potential in advanced HCC. Whether ATO regulates angiogenesis and can be used to prevent tumor progression in HCC after insufficient RFA is still unknown. METHODS: Insufficient RFA was simulated using a water bath. MTT assay and tube formation assay were used to evaluate the effects of ATO on viability and proangiogenic abilities of SMMC7721 and HepG2 cells after insufficient RFA in vitro. The molecular changes with the treatment of ATO were evaluated through Western blot. An ectopic nude mice model was used to evaluate the effect of ATO on the tumor of SMMC7721 cells in vivo after insufficient RFA. RESULTS: In this study, HepG2 and SMMC7721 cells after insufficient RFA (named HepG2-H and SMMC7721-H, respectively) showed higher proliferation than the untreated cells and promoted tube formation of endothelial cells in a paracrine manner. ATO eliminated the difference in proliferation between untreated and RFA-treated cells and suppressed angiogenesis induced by HCC cells after insufficient RFA through the Ang-1 (angiopoietin-1)/Ang-2 (angiopoietin-2)/Tie2 pathway. Hif-1α overexpression abolished the inhibitory effect of ATO on angiogenesis in HCC after insufficient RFA. ATO inhibited tumor growth and angiogenesis in HCC after insufficient RFA. CONCLUSIONS: Our results demonstrate that ATO blocks the paracrine signaling of Ang-1 and Ang-2 by inhibiting p-Akt/Hif-1α and further suppresses the angiogenesis of HCC after insufficient RFA.

Does electroacupuncture benefit mixed urinary incontinence? A systematic review and meta-analysis with trial sequential analysis.

INTRODUCTIN AND HYPOTHESIS: Mixed urinary incontinence (MUI) comprises a combination of urgency and stress. The efficacy and safety of electroacupuncture (EA) for the treatment of MUI remain unclear. OBJECTIVE: To assess the efficacy and safety of EA in treating MUI. METHODS: We searched PubMed, CENTRAL, Embase, Web of Science, four Chinese databases, clinical research registration platforms, grey literature, and the reference lists of the selected studies. Risk of bias and quality were evaluated using the Revman 5.4 and Jadad scores. Meta-analysis was performed using Stata 15.1 software. Trial sequential analysis (TSA) was used to assess the stability of the results. RESULTS: Eight randomized controlled trials comprising 847 patients were included. The meta-analysis results showed that compared with antimuscarinic drugs plus pelvic floor muscle training, EA resulted in significantly less pad weight on the 1-h pad test and statistically significantly lower severity scores on the International Consultation on Incontinence Questionnaire Short Form. The change in the 72-h incontinence episode frequency difference was not statistically significant, and there was no outcome of overall response rate and quality of life in this meta-analysis. Few adverse events occurred in the EA group. The TSA results suggested that the result of change from baseline in the 1-h pad test was stable and the evidence was conclusive. CONCLUSIONS: EA could be a potential treatment option for MUI and is relatively safe. Nevertheless, because of the limitations of this study, our conclusions should be interpreted with caution, and further studies are needed to confirm the comprehensive clinical efficacy and placebo effect of EA.

Toward near-white-light electroluminescence from n-ZnO nanocrystals/n-Si isotype heterojunctions via an AZO spectral scissor.

A strategy to realize ZnO-based near-white-light electroluminescence (EL) was proposed by utilizing and regulating the intrinsic defect-related emissions of solution-processed ZnO nanocrystals (NCs). Prototype near-white light-emitting diodes (LEDs) based upon this strategy were demonstrated by using n-ZnO NCs/n-Si isotype heterojunctions. The emission color of the n-ZnO NCs/n-Si isotype heterojunction LEDs was tuned toward near white by using an Al-doped ZnO (AZO) spectral "scissor" which can tailor the green light more severely, rather than the blue or red light. Moreover, quantum size effect was clearly observed in both the photoluminescence (PL) and EL spectra via the redshift of the near-band-edge UV emission of the ZnO NCs. The strategy using AZO spectral "scissors" to regulate the VO-related green emission of ZnO may present a promising pathway to realize ZnO-based white-light LEDs.

The Protective and Immunomodulatory Effects of Fucoidan Against 7,12-Dimethyl benz[a]anthracene-Induced Experimental Mammary Carcinogenesis Through the PD1/PDL1 Signaling Pathway in Rats.

Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively. We found that fucoidan treatment decreased the tumor incidence and mean tumor weight and prolonged the tumor latency. Flow cytometric analyses revealed that the number of blood natural killer cells was higher after fucoidan treatment and that the proportions of CD4 and CD8 T cells were also increased. The serum levels of interleukin (IL)-6, IL-12p40, and interferon (IFN)-γ were higher in the rats treated with fucoidan compared to those of model rats. Moreover, the percentage of CD3+ Foxp3+ regulatory T cells in the blood and the levels of IL-10 and transforming growth factor ß in the serum were lower in the rats treated with fucoidan. Furthermore, fucoidan treatment decreased the expression of Foxp3 and programmed cell death 1 ligand 1 (PDL1) in tumor tissues. The levels of p-phosphatidyl inositol kinase 3 and p-AKT in tumor tissues were also lower than those of model rats. These results suggest that a fucoidan-supplemented diet can inhibit DMBA-induced tumors in rats. This study provides experimental evidence toward elucidating the immune enhancement induced by fucoidan through the programmed cell death 1/PDL1 signaling pathway. The immunomodulatory effect is one of the possible mechanisms of the protective effect of fucoidan against mammary carcinogenesis.

An attempt to confirm the contribution to ORR activity of different N-species in M-NC (M = Fe, Co, Ni) catalysts with XPS analysis.

M-NC catalysts were prepared by a combination of the electrospinning method and thermal treatment. For the first time, the contribution of N-species to the ORR (oxygen reduction reaction) of the M-NC was analysed using XPS (X-ray photoelectron spectroscopy). The obtained relations were verified by VASP (Vienna Ab-initio Simulation Package).

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, the process of formation of new blood vessels, is required for cancer cells to obtain nutrients and oxygen. HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth, progression, invasion, and metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR), and are considered effective strategies for HCC, particularly advanced HCC. However, because the survival benefits conferred by these anti-angiogenic therapies are modest, new anti-angiogenic targets must be identified. Several recent studies have determined the underlying molecular mechanisms, including pro-angiogenic factors secreted by HCC cells, the tumor microenvironment, and cancer stem cells. In this review, we summarize the roles of pro-angiogenic factors; the involvement of endothelial cells, hepatic stellate cells, tumor-associated macrophages, and tumor-associated neutrophils present in the tumor microenvironment; and the regulatory influence of cancer stem cells on angiogenesis in HCC. Furthermore, we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC. A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

Complete mitochondrial DNA sequence of Tupaia belangeri yaoshanensis (Wang, 1987) from Dayao Mountains in China.

The tree shrew (Tupaia belangeri) is currently placed in the order Scandentia. Owing to their unique characteristics, such as small body size, high brain-to-body mass ratio, short reproductive cycle and life span, and low maintenance costs in laboratory conditions, tree shrews have been proposed as alternative experimental animals to primates in biomedical research. In this study, we determined the complete mitochondrial genome of the subspecies Tupaia belangeri yaoshanensis (T.b. yaoshanensis). The mitochondrial DNA (mtDNA) is 16,777 bp long and contains 13 protein-coding genes (PCGs), two ribosomal RNA genes (12S and 16S), and 22 transfer RNA (tRNA) genes. The base composition of the mitogenome was A (32.28%), T (26.82%), G (14.79%), and C (26.11%). For the 13 PCGs, 1405 variable sites were found between T.b. yaoshanensis and T.b. chinensis (JN800724), of which 916 were synonymous and 489 were nonsynonymous. The frequency of mutations significantly varied among the different genes, with the highest value in the mt-NAD5 gene of tree shrews. Phylogenetic analysis based on the amino acid sequences of 13 PCGs revealed a closer relationship between the species of Scandentia and Lagomorpha. To the best of our knowledge, this is the first study to report the complete mitochondrial genome sequence of T.b. yaoshanensis.

Prediction of DNA rejoining kinetics and cell survival after proton irradiation for V79 cells using Geant4-DNA.

PURPOSE: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. METHODS: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. RESULTS: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. CONCLUSION: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

Implementation of the EPICS2017 database for photons in Geant4.

This paper describes in detail the implementation of Geant4 Livermore electromagnetic physics models based on the EPICS2017 database for the low energy transport of photons. These models describe four photon processes: gamma conversion, Compton scattering, photoelectric effect and Rayleigh scattering. New parameterizations based on EPICS2017 were performed for scattering functions of Compton effect, subshell cross-sections of the photoelectric effect and form factors of Rayleigh scattering, in order to improve the precision of fitted values compared to tabulated values. Comparisons between new and old parameterizations were also carried out to evaluate the precision of the new parameterizations. The models were tested through a comparative study, in which the mass attenuation coefficient was calculated for both total photon interaction and each process using Geant4 simulations based on EPICS2017 and EPDL97 respectively. The results obtained from the simulations were found in good agreement with the XCOM reference data.

A Geant4 simulation of X-ray emission for three-dimensional proton imaging of microscopic samples.

PURPOSE: Proton computed microtomography is a technique that reveals the inner content of microscopic samples. The density distribution of the material (in g·cm-3) is obtained from proton transmission tomography (STIM: Scanning Transmission Ion Microscopy) and the element content from X-ray emission tomography (PIXE: Particle Induced X-ray Emission). A precise quantification of chemical elements is difficult for thick samples, because of the variations of X-ray production cross-sections and of X-ray absorption. Both phenomena are at the origin of an attenuation of the measured X-ray spectra, which leads to an underestimation of the element content. Our aim is to quantify the accuracy of a specific correction method that we designed for thick samples. METHODS: In this study, we describe how the 3D variations in the mass density were taken into account in the reconstruction code, in order to quantify the correction according to the position of the proton beam and the position and aperture angle of the X-ray detector. Moreover, we assess the accuracy of the reconstructed densities using Geant4 simulations on numerical phantoms, used as references. RESULTS: The correction process was successfully applied and led, for the largest regions of interest (little affected by partial volume effects), to an accuracy ≤ 4% for phosphorus (compared to about 40% discrepancy without correction). CONCLUSION: This study demonstrates the accuracy of the correction method implemented in the tomographic reconstruction code for thick samples. It also points out some advantages offered by Geant4 simulations: i) they produce projection data that are totally independent of the inversion method used for the image reconstruction; ii) one or more physical processes (X-ray absorption, proton energy loss) can be artificially turned off, in order to precisely quantify the effect of the different phenomena involved in the attenuation of X-ray spectra.

A review of recent strategies to improve the physical stability of phycocyanin.

There is an increasing demand for more healthy and sustainable diets, which led to an interest in replacing synthetic colors with natural plant-based ones. Phycocyanin, which is commonly extracted from Spirulina platensis, has been explored as a natural blue pigment for application in the food industry. It is also used as a nutraceutical in food, cosmetic, and pharmaceutical products because of its potentially beneficial biological properties, such as radical scavenging, immune modulating, and lipid peroxidase activities. The biggest challenges to the widespread application of phycocyanin for this purpose are its high sensitivity to chemical degradation when exposed to heat, light, acids, high pressure, heavy metal cations, and denaturants. Consequently, it is of considerable importance to improve its chemical stability, which requires a thorough knowledge of the relationship between the structure, environment, and chemical reactivity of phycocyanin. To increase the application of this natural pigment and nutraceutical within foods and other products, the structure, biological activities, and factors affecting its stability are reviewed, as well as strategies that have been developed to improve its stability. The information contained in this article is intended to stimulate further studies on the development of effective strategies to improve phycocyanin stability and performance.