TnpB homologues exapted from transposons are RNA-guided transcription factors.

Transposon-encoded tnpB and iscB genes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination1-4. These widespread gene families were repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas12 (refs. 5,6). We set out to test the hypothesis that TnpB nucleases may have also been repurposed for novel, unexpected functions other than CRISPR-Cas adaptive immunity. Here, using phylogenetics, structural predictions, comparative genomics and functional assays, we uncover multiple independent genesis events of programmable transcription factors, which we name TnpB-like nuclease-dead repressors (TldRs). These proteins use naturally occurring guide RNAs to specifically target conserved promoter regions of the genome, leading to potent gene repression in a mechanism akin to CRISPR interference technologies invented by humans7. Focusing on a TldR clade found broadly in Enterobacteriaceae, we discover that bacteriophages exploit the combined action of TldR and an adjacently encoded phage gene to alter the expression and composition of the host flagellar assembly, a transformation with the potential to impact motility8, phage susceptibility9, and host immunity10. Collectively, this work showcases the diverse molecular innovations that were enabled through repeated exaptation of transposon-encoded genes, and reveals the evolutionary trajectory of diverse RNA-guided transcription factors.

Transposon-encoded nucleases use guide RNAs to promote their selfish spread.

Insertion sequences are compact and pervasive transposable elements found in bacteria, which encode only the genes necessary for their mobilization and maintenance1. IS200- and IS605-family transposons undergo 'peel-and-paste' transposition catalysed by a TnpA transposase2, but they also encode diverse, TnpB- and IscB-family proteins that are evolutionarily related to the CRISPR-associated effectors Cas12 and Cas9, respectively3,4. Recent studies have demonstrated that TnpB and IscB function as RNA-guided DNA endonucleases5,6, but the broader biological role of this activity has remained enigmatic. Here we show that TnpB and IscB are essential to prevent permanent transposon loss as a consequence of the TnpA transposition mechanism. We selected a family of related insertion sequences from Geobacillus stearothermophilus that encode several TnpB and IscB orthologues, and showed that a single TnpA transposase was broadly active for transposon mobilization. The donor joints formed upon religation of transposon-flanking sequences were efficiently targeted for cleavage by RNA-guided TnpB and IscB nucleases, and co-expression of TnpB and TnpA led to substantially greater transposon retention relative to conditions in which TnpA was expressed alone. Notably, TnpA and TnpB also stimulated recombination frequencies, surpassing rates observed with TnpB alone. Collectively, this study reveals that RNA-guided DNA cleavage arose as a primal biochemical activity to bias the selfish inheritance and spread of transposable elements, which was later co-opted during the evolution of CRISPR-Cas adaptive immunity for antiviral defence.

Platelet-rich fibrin as an apical barrier for MTA placement in the treatment of teeth with open apices: a pilot study.

OBJECTIVE: The aim of the present pilot study was to assess the effectiveness of the platelet-rich fibrin (PRF) apical barrier for the placement of MTA for the treatment of teeth with periapical lesions and open apices. METHODS: A total of thirty teeth on twenty-eight patients with open apices and periapical periodontitis were enrolled and divided into two groups in the present pilot study. In the PRF group (fourteen teeth in thirteen patients), nonsurgical endodontic treatment was performed using PRF as an apical matrix, after which the apical plug of the MTA was created. For the non-PRF group (fourteen teeth in fourteen patients), nonsurgical endodontic therapy was performed using only the MTA for an apical plug with no further periapical intervention. Clinical findings and periapical digital radiographs were used for evaluating the healing progress after periodic follow-ups of 1, 3, 6, and 9 months. The horizontal dimension of the periapical lesion was gauged, and the changes in the dimensions were recorded each time. The Friedman test, Dunn-Bonferroni post hoc correction, and Mann-Whitney U test were used for statistical analysis, with P < 0.05 serving as the threshold for determining statistical significance. RESULTS: All patients in both groups in the present pilot study had no clinical symptoms after 1 month, with a significant reduction in the periapical lesion after periodic appointments. The lesion width of the PRF group was significantly smaller than that of the non-PRF group in the sixth and ninth month after treatment. CONCLUSIONS: PRF is a promising apical barrier matrix when combined with MTA for the treatment of teeth with open apices and periapical periodontitis. Small number of study subjects and the short time of follow-up period limit the generalizability of these results. TRIAL REGISTRATION: TCTR, TCTR20221109006. Registered 09 November 2022 - Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20221109006 .

Synthesis and Photophysical Characterization of a pH-Sensitive Quadracyclic Uridine (qU) Analogue.

Fluorescent base analogues (FBAs) have become useful tools for applications in biophysical chemistry, chemical biology, live-cell imaging, and RNA therapeutics. Herein, two synthetic routes towards a novel FBA of uracil named qU (quadracyclic uracil/uridine) are described. The qU nucleobase bears a tetracyclic fused ring system and is designed to allow for specific Watson-Crick base pairing with adenine. We find that qU absorbs light in the visible region of the spectrum and emits brightly with a quantum yield of 27 % and a dual-band character in a wide pH range. With evidence, among other things, from fluorescence lifetime measurements we suggest that this dual emission feature results from an excited-state proton transfer (ESPT) process. Furthermore, we find that both absorption and emission of qU are highly sensitive to pH. The high brightness in combination with excitation in the visible and pH responsiveness makes qU an interesting native-like nucleic acid label in spectroscopy and microscopy applications in, for example, the field of mRNA and antisense oligonucleotide (ASO) therapeutics.

Tuning Selectivity and Stability in Heteroleptic Lanthanide Adducts by Ligand Design.

Terdentate ligands L10-L14 and their heteroleptic [LkLn(hfac)3] complexes (Ln = La, Eu, Gd, Er, or Y; H-hfac = 1,1,1,5,5,5-hexafluoropentane-2,4-dione) exhibit multifactorial correlations between the ligand's structural frameworks, including their level of preorganization and steric congestion and their affinities and selectivities for catching the trivalent lanthanide containers [Ln(hfac)3]. The polyaromatic ligand scaffolds could be stepwise modulated via lanthanide-template synthetic strategies, using intermolecular rhodium-catalyzed insertion reactions. The increasing level of preorganization along the L10 → L11 → L12 series leads to a duality in which larger thermodynamic formation constants with lanthanides in CD2Cl2 are accompanied by an unexpected decrease in the Ln-N affinities in the solid state, which could be assigned to a limited match between the lanthanide size and the enlarged preorganized cavities. On the contrary, a reduced stability is induced by the connection of additional methyl groups at position 1 of the benzimidazole moieties in L13 and L14, which is accompanied by an optimization of metal-nitrogen bond lengths. This study contributes to the rational design of highly stable neutral heteroleptic lanthanide ß-diketonate adducts that resist dissociation in solution, a prerequisite for photophysical applications using these highly luminescent systems at the molecular level.

Platelet rich fibrin and MTA in the treatment of teeth with open apices.

BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.

In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.

PURPOSE: To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging. METHODS: Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30° retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD. RESULTS: Mean age was 75.17 ± 2.51 years in the SDD group (3 males, 3 females) versus 73.17 ± 3.15 years in the healthy control group (p = 0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean ± standard deviation foci detected (i.e., cone photoreceptors) was 7123.75 ± 3683.32 foci/mm2 in the SDD group versus 13,253 ± 3331.00 foci/mm2 in the healthy control group (p = 0.0003). The number of SDD was associated with a reduction in foci density, p = 0.0055, r = - 0.7622. CONCLUSION: The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.

Journey in the Impure Land: Buddhist Pilgrimage and Perceptions of Life and Old Age in Vietnam.

Religiously inspired travel has burgeoned in Vietnam in recent years, amidst rapid economic development and a booming tourist industry. Buddhist pilgrimages particularly attract older women, who compose the majority of temple goers in Vietnam. Having lived through volatile historical periods of war, economic hardship, and political transformations, travelling on pilgrimage is the first opportunity for many older Vietnamese women to enjoy new places and experiences. Drawing on data collected during my field research among Buddhist women pilgrims in their sixties and seventies from Ho Chi Minh City, I show how pilgrimage is seen as a journey of a lifetime and how it reflects the perception of life and self-transformation along the life course. Drawing on Victor and Edith Turner's (1978 [2011]) discussion of pilgrimage as the antistructure of everyday social life, this paper explains why pilgrimage is markedly different from other life experiences of Vietnamese women, and how religious travel positions old age not as the culmination of self-development, but rather as an ongoing process of gaining wisdom.

Cell-matrix and cell-cell interaction mechanics in guiding migration.

Physical properties of tissue are increasingly recognised as major regulatory cues affecting cell behaviours, particularly cell migration. While these properties of the extracellular matrix have been extensively discussed, the contribution from the cellular components that make up the tissue are still poorly appreciated. In this mini-review, we will discuss two major physical components: stiffness and topology with a stronger focus on cell-cell interactions and how these can impact cell migration.

Novel method to assess resident alveolar macrophage efferocytosis of apoptotic neutrophils by flow cytometry.

Macrophage efferocytosis of apoptotic neutrophils (PMNs) plays a key role in the resolution of inflammation. In these studies, we describe a novel flow cytometric method to assess efferocytosis of apoptotic PMNs. Resident alveolar macrophages and PMNs were collected from lungs of mice exposed to inhaled ozone (0.8 ppm, 3 h) followed by lipopolysaccharide (3 mg/kg, i.v.) to induce acute lung injury. PMNs were labeled with PKH26 or DilC18(5)-DS (D12730) cell membrane dye and then incubated with resident alveolar macrophages at a ratio of 5:1. After 90 min, macrophage efferocytosis was analyzed by flow cytometry and confirmed by confocal microscopy. Whereas alveolar macrophages incubated with D12730-labeled PMNs could readily be identified as efferocytotic or non-efferocytotic, this was not possible with PKH26 labeled PMNs due to confounding macrophage autofluorescence. Using D12730 labeled PMNs, subsets of resident alveolar macrophages were identified with varying capacities to perform efferocytosis, which may be linked to the activation state of these cells. Future applications of this method will be useful in assessing the role of efferocytosis in the resolution of inflammation in response to toxicant exposure.

Promoting High-Oxidation-State Metal Active Sites in a Hollow Ternary Metal Fluoride Nanoflake Array for Urea Electrolysis.

The adsorption ability of hydrogen, hydroxide, and oxygenic intermediates plays a crucial role in electrochemical water splitting. Electron-deficient metal-active sites can prompt electrocatalytic activity by improving the adsorption ability of intermediates. However, it remains a significant challenge to synthesize highly abundant and stable electron-deficient metal-active site electrocatalysts. Herein, we present a general approach to synthesizing a hollow ternary metal fluoride (FeCoNiF2) nanoflake array as an efficient and robust bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and urea oxidation reaction (UOR). We find that the F anion withdraws electrons from the metal centers, inducing an electron-deficient metal center catalyst. The rationally designed hollow nanoflake array exhibits the overpotential of 30 mV for HER and 130 mV for UOR at a current density of 10 mA cm-2 and superior stability without decay events over 150 h at a large current density of up to 100 mA cm-2. Remarkably, the assembled urea electrolyzer using a bifunctional hollow FeCoNiF2 nanoflake array catalyst requires cell voltages of only 1.352 and 1.703 V to afford current densities of 10 and 100 mA cm-2, respectively, which are 116 mV less compared with that required for overall water splitting.

Synthesis and biological evaluation of tert-butyl ester and ethyl ester prodrugs of L-γ-methyleneglutamic acid amides for cancer.

In cancer cells, glutaminolysis is the primary source of biosynthetic precursors. Recent efforts to develop amino acid analogues to inhibit glutamine metabolism in cancer have been extensive. Our lab recently discovered many L-γ-methyleneglutamic acid amides that were shown to be as efficacious as tamoxifen or olaparib in inhibiting the cell growth of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells after 24 or 72 h of treatment. None of these compounds inhibited the cell growth of nonmalignant MCF-10A breast cells. These L-γ-methyleneglutamic acid amides hold promise as novel therapeutics for the treatment of multiple subtypes of breast cancer. Herein, we report our synthesis and evaluation of two series of tert-butyl ester and ethyl ester prodrugs of these L-γ-methyleneglutamic acid amides and the cyclic metabolite and its tert-butyl esters and ethyl esters on the three breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 and the nonmalignant MCF-10A breast cell line. These esters were found to suppress the growth of the breast cancer cells, but they were less potent compared to the L-γ-methyleneglutamic acid amides. Pharmacokinetic (PK) studies were carried out on the lead L-γ-methyleneglutamic acid amide to establish tissue-specific distribution and other PK parameters. Notably, this lead compound showed moderate exposure to the brain with a half-life of 0.74 h and good tissue distribution, such as in the kidney and liver. Therefore, the L-γ-methyleneglutamic acid amides were then tested on glioblastoma cell lines BNC3 and BNC6 and head and neck cancer cell lines HN30 and HN31. They were found to effectively suppress the growth of these cancer cell lines after 24 or 72 h of treatment in a concentration-dependent manner. These results suggest broad applications of the L-γ-methyleneglutamic acid amides in anticancer therapy.

Multiphoton characterization and live cell imaging using fluorescent adenine analogue 2CNqA.

Fluorescent nucleobase analogues (FBAs) are established tools for studying oligonucleotide structure, dynamics and interactions, and have recently also emerged as an attractive option for labeling RNA-based therapeutics. A recognized drawback of FBAs, however, is that they typically require excitation in the UV region, which for imaging in biological samples may have disadvantages related to phototoxicity, tissue penetration, and out-of-focus photobleaching. Multiphoton excitation has the potential to alleviate these issues and therefore, in this work, we characterize the multiphoton absorption properties and detectability of the highly fluorescent quadracyclic adenine analogue 2CNqA as a ribonucleotide monomer as well as incorporated, at one or two positions, into a 16mer antisense oligonucleotide (ASO). We found that 2CNqA has a two-photon absorption cross section that, among FBAs, is exceptionally high, with values of σ2PA(700 nm) = 5.8 GM, 6.8 GM, and 13 GM for the monomer, single-, and double-labelled oligonucleotide, respectively. Using fluorescence correlation spectroscopy, we show that the 2CNqA has a high 2P brightness as the monomer and when incorporated into the ASO, comparing favorably to other FBAs. We furthermore demonstrate the usefulness of the 2P imaging mode for improving detectability of 2CNqA-labelled ASOs in live cells.

LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING ANGIOID STREAKS.

PURPOSE: To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era. METHODS: Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT"). RESULTS: Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively. CONCLUSION: Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.

CHOROIDAL VASCULARITY INDEX IN HYDROXYCHLOROQUINE TOXIC RETINOPATHY: A Quantitative Comparative Analysis Using Enhanced Depth Imaging In Spectral Domain Optical Coherence Tomography.

PURPOSE: To investigate choroidal involvement in eyes of patients treated with hydroxychloroquine (HCQ), by quantifying the choroidal vascularity index (CVI) and other choroidal biomarkers. METHODS: Vertical enhanced depth imaging spectral domain optical coherence tomography (SD-OCT) scans were performed in eyes with either advanced-stage or mild HCQ toxic retinopathy, as well as in healthy age-matched and sex-matched controls. Based on SD-OCT scans, the subfoveal and mean choroidal thickness (ChT) was measured. The CVI, total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were calculated based on a binarization image process. These variables were computed and compared between the three groups (i.e., advanced stage, mild toxicity, and healthy controls). RESULTS: Forty-eight eyes of 47 patients under HCQ (26 eyes presented with advanced stage HCQ toxicity and 22 eyes with mild toxicity) and 34 eyes of 31 healthy controls were included. Both CVI and ChT were significantly different between the three groups ( P < 0.001, P < 0.001). When comparing the advanced stage toxicity group to healthy controls, both the subfoveal and the mean ChT were diminished ( P < 0.001). The CVI, TCA, LCA, and SCA were significantly lower in the advanced stage of toxicity group when compared with controls ( P < 0.001, <0.00001, <0.0001, and P = 0.0094, respectively). CONCLUSION: Our study suggests that eyes with HCQ toxic retinopathy, especially at advanced stages, present with choroidal impairment, giving further pathophysiological insights into the unfolding of this retinal toxicity.

Intermolecular dark resonance energy transfer (DRET): upgrading fluorogenic DNA sensing.

The sensitivity of FRET-based sensing is usually limited by the spectral overlaps of the FRET donor and acceptor, which generate a poor signal-to-noise ratio. To overcome this limitation, a quenched donor presenting a large Stokes shift can be combined with a bright acceptor to perform Dark Resonance Energy Transfer (DRET). The consequent fluorogenic response from the acceptor considerably improves the signal-to-noise ratio. To date, DRET has mainly relied on a donor that is covalently bound to the acceptor. In this context, our aim was to develop the first intermolecular DRET pair for specific sensing of nucleic acid sequences. To this end, we designed DFK, a push-pull probe based on a fluorenyl π-platform that is strongly quenched in water. DFK was incorporated into a series of oligonucleotides and used as a DRET donor with Cy5-labeled complementary sequences. In line with our expectations, excitation of the dark donor in the double-labeled duplex switched on the far-red Cy5 emission and remained free of cross-excitation. The DRET mechanism was supported by time-resolved fluorescence measurements. This concept was then applied with binary probes, which confirmed the distance dependence of DRET as well as its potency in detecting sequences of interest with low background noise.

Isolation of Two Plasticizers, Bis(2-ethylhexyl) Terephthalate and Bis(2-ethylhexyl) Phthalate, from Capparis spinosa L. Leaves.

Many plants have been known to be contaminated and accumulate plasticizers from the environment, including water sources, soil, and atmosphere. Plasticizers are used to confer elasticity and flexibility to various fiber and plastic products. Consumption of plasticizers can lead to many adverse effects on human health, including reproductive and developmental toxicity, endocrine disruption, and cancer. Herein, we report for the first time that two plasticizers, bis(2-ethylhexyl) terephthalate (DEHT) and bis(2-ethylhexyl) phthalate (DEHP), have been isolated from the leaves of Capparis spinosa L. (the caper bush), a plant that is widely used in food seasonings and traditional medicine. 297 mg/kg of DEHT and 48 mg/kg of DEHP were isolated from dried and grounded C. spinosa L. leaves using column chromatography and semi-preparative high-performance liquid chromatography. Our study adds to the increase in the detection of plasticizers in our food and medicinal plants and to the alarming concern about their potential adverse effects on human health.

Reconstruction of Large Anterior Skull Base Defects After Resection of Sinonasal Tumors With Intracranial Extension by Using Pedicled Double Flap Techniques.

INTRODUCTION: The use of surgical resection for large anterior skull base (ASB) tumors and sinonasal malignancies with intracranial extension will result in a large skull base defect. Reconstruction of large ASB defects using traditional techniques is high risk and may lead to postoperative cerebral spinal fluid (CSF) leakage, meningitis, and an increase in mortality rate. The use of a pedicled double flap technique to reconstruct the ASB defect may decrease complications. This study presents the clinical outcomes of patients who underwent double flap reconstruction techniques after resection of their sinonasal malignancies with significant intracranial extension at Cho Ray hospital in Vietnam. METHODS: The case series study was conducted at Cho Ray hospital from September 2010 to September 2020. All patients with large sinonasal malignancies that invaded intracranially underwent transnasal endoscopic surgery and subfrontal craniotomy. Reconstruction of large skull base defects (>2 cm) were followed up by using the pedicled double flaps technique. This study was performed in line with the principles of the Declaration of Helsinki. Approval of the study was granted by the Independent Ethics Committee of Cho Ray Hospital (Date: March 3, 2014/No: 11/BVCRHDDD). RESULTS: During September 2010 to September 2020, there were 75 patients who underwent a modified multilayer, double flap reconstruction technique after the resection of their ASB tumor. Skull base defects were commonly seen along the horizontal plate of the ethmoid bone and the ethmoid roof (98.6%). Large skull base defects (>2 cm) accounted for 81.3% of cases. Overall, the risk of postoperative CSF leakage and meningitis after double flap repair was considerably low. Of all participants, only 1 experienced postoperative CSF leakage and 1 experienced postoperative meningitis. Despite the complications, these patients improved significantly and remained stable. CONCLUSION: The use of double vascularized pedicled flaps may decrease the incidence of postoperative CSF leakage and meningitis. This technique is an effective method for the reconstruction of ASB tumors with large defects.

Comparison of the radioprotective effects of the liposomal forms of five natural radioprotectants in alleviating the adverse effects of ionising irradiation on human lymphocytes and skin cells in radiotherapy.

This study aims to evaluate the radioprotective effects of liposomes encapsulating curcumin (Lip-CUR), silibinin (Lip-SIL), α-tocopherol (Lip-TOC), quercetin (Lip-QUE) and resveratrol (Lip-RES) in alleviating the adverse effects of ionising irradiation on human lymphoctyes and skin cells in radiotherapy. Liposomes encapsulating the above natural radioprotectants (Lip-NRPs) were prepared by the film hydration method combined with sonication. Their radioprotective effects for the cells against X-irradiation was evaluated using trypan-blue assay and γ-H2AX assay. All prepared Lip-NRPs had a mean diameter less than 240 nm, polydispersity index less than 0.32, and zeta potential more than -23 mV. Among them, the radioprotective effect of Lip-RES was lowest, while that of Lip-QUE was highest. Lip-SIL also exhibited a high radioprotective effect despite its low DPPH-radical scavenging activity (12.9%). The radioprotective effects of Lip-NRPs do not solely depend on the free radical scavenging activity of NRPs but also on their ability to activate cellular mechanisms.

Assessment of agricultural pesticide inert ingredient transport following modeling approach: Case study of two formulation agents in Sacramento River watershed.

This research provides the first assessment of the environmental fate and transport of agricultural pesticide formulation agents following a dynamic modeling approach. Two formulation agents of toxicological concern, Naphthalene and Solvent Naphtha (Petroleum), Heavy Aromatic, were simulated from their usage in commercially-applied pesticides. The Soil and Water Assessment Tool (SWAT) was applied to simulate these formulation agents during 2011-2014 in the agriculturally intensive Sacramento River watershed. The sensitivity and uncertainty of some key parameters were analyzed. The predicted transport masses of these formulation agents in surface water were strongly associated with rainfall. While predicted transport masses were quite small at the watershed scale (<0.01% of applied masses), they were 26-31 times higher in certain locales at the subbasin level. Since many formulation agents are widely used in pesticides throughout this and other agriculturally impacted watersheds, their potential risks in the environment need more thorough investigation by modeling and monitoring, especially for areas with heavy usage.