An Endoplasmic Reticulum Targeting Type I Photosensitizer for Effective Photodynamic Therapy against Hypoxic Tumor Cells

Organelle-targeted type I photodynamic therapy (PDT) shows great potential to overcome the hypoxic microenvironment in solid tumors. The endoplasmic reticulum (ER) is an indispensable organelle in cells with important biological functions. When the ER is damaged due to the production of reactive oxygen species (ROS), the accumulation of misfolded proteins will interfere with ER homeostasis, resulting in ER stress. Here, an ER-targeted benzophenothiazine-based photosensitizer NBS-ER was presented. ER targeting modification significantly reduced the dark toxicity and improved phototoxicity index (PI). NBS-ER could effectively produce O₂⁻⋅ with near-infrared irradiation, making its phototoxicity under hypoxia close to that under normoxia. Meanwhile, the photoinduced ROS triggered ER stress and induced apoptosis. In addition, NBS-ER possessed excellent photodynamic therapeutic effect in 4T1-tumor-bearing mice.     

One Way Traffic: Base-to-Backbone Hole Transfer in Nucleoside Phosphorodithioate

The directionality of the hole-transfer processes between DNA backbone and base was investigated by using phosphorodithioate [P(S⁻)=S] components. ESR spectroscopy in homogeneous frozen aqueous solutions and pulse radiolysis in aqueous solution at ambient temperature confirmed initial formation of G^.+-P(S⁻)=S. The ionization potential of G-P(S⁻)=S was calculated to be slightly lower than that of guanine in 5′-dGMP. Subsequent thermally activated hole transfer from G^.+ to P(S⁻)=S led to dithiyl radical (P-2S^.) formation on the μs timescale. In parallel, ESR spectroscopy, pulse radiolysis, and density functional theory (DFT) calculations confirmed P-2S^. formation in an abasic phosphorodithioate model compound. ESR investigations at low temperatures and higher G-P(S⁻)=S concentrations showed a bimolecular conversion of P-2S^. to the σ²-σ*¹-bonded dimer anion radical [-P-2S 2S-P-]⁻ [ΔG (150 K, DFT)=−7.2 kcal mol⁻¹]. However, [-P-2S 2S-P-]⁻ formation was not observed by pulse radiolysis [ΔG° (298 K, DFT)=−1.4 kcal mol⁻¹]. Neither P-2S^. nor [-P-2S 2S-P-]⁻ oxidized guanine base; only base-to-backbone hole transfer occurs in phosphorodithioate.     

An interview with Sam C. Saunders

Sam C. Saunders, the son of Elizabeth Cundiff and Winston E. Saunders, was born in Richland, OR, on February 24, 1931. The family moved to La Grande, OR, in 1944, where Sam completed high school and two years at Eastern Oregon College. He then received the BSc degree in Mathematics from the University of Oregon, Eugene, OR, in 1952, and he attended the University of Washington, Seattle, WA, receiving a PhD degree under Z. W. Birnbaum. After graduating, he accepted employment at the Boeing Company in its Mathematical Services Unit and, in 1972, a position as a Full Professor at Washington State University, Pullman, WA, from which he retired in 1996.     

Logging damage and injured tree mortality in tropical forest management

Using insights from the forest ecology literature, we analyze the effect of injured trees on stand composition and carbon stored in above‐ground biomass and the implications for forest management decisions. Results from a Faustmann model with data for a tropical forest on Kalimantan show that up to 50% of the basal area of the stand before harvest can consist of injured trees. Considering injured trees leads to an increase in the amount of carbon in above‐ground biomass of up to 165%. These effects are larger under reduced impact logging than under conventional logging. The effects on land expectation value and cutting cycle are relatively small. The results suggest that considering injured trees in models for tropical forest management is important for the correct assessment of the potential of financial programs to store carbon and conserve forest ecosystem services in managed tropical forests, such as reducing emissions from deforestation and forest degradation and payment for ecosystem services. Recommendations for Resource Managers

• Considering the role of injured trees is important for managing tropical forests
• These trees can cover up to 50% of basal area and contain more than 50% of the carbon stored in above‐ground biomass
• Reduced impact logging leads to a larger basal area of injured trees and more carbon stored in injured trees than conventional logging
• Injured trees play an important role when assessing the potential for carbon storage in the context of payment for forest ecosystem services.

     

Can a Six‐Letter Alphabet Increase the Likelihood of Photochemical Assault to the Genetic Code?

In 2014, two unnatural nucleosides, d5SICS and dNaM, were shown to selectively base pair and replicate with high fidelity in a modified strain of E. coli, thus effectively expanding its genetic alphabet from four to six letters. More recently, a significant reduction in cell proliferation was reported in cells cultured with d5SICS, and putatively with dNaM, upon exposure to brief periods of near‐visible radiation. The photosensitizing properties of the lowest‐energy excited triplet state of both d5SICS and dNaM were implicated in their cytotoxicity. Importantly, however, the excited‐state mechanisms by which near‐visible excitation populates the triplet states of d5SICS and dNaM are currently unknown. In this study, steady‐state and time‐resolved spectroscopies are combined with quantum‐chemical calculations in order to reveal the excited‐state relaxation mechanisms leading to efficient population of the triplet states in these unnatural nucleosides in solution. It is shown that excitation of d5SICS or dNaM with near‐visible light leads overwhelmingly to ultrafast population of their triplet states on the femtosecond time scale. The results presented in this work lend strong support to the proposal that photoexcitation of these unnatural nucleosides can accelerate oxidatively generated damage to DNA and other biomolecules within the cellular environment.     

Microstructure change in deuterium implanted CLAM steel induced by electron irradiation

As Reduced Activation Ferritic/Martensitic (RAFM) steel is considered the primary candidate for use as a structural material in fusion power reactors,many countries are developing different kinds of RAFM.China is developing new CLAM (China Low Activation Martensitic) steel.The study investigates microstructural changes in CLAM steel implanted with deuterium ions induced by 1250 keV electron irradiation from R.T.to 873 K,and observes both the growth and shrinkage of the defect clusters produced by deuterium ...     

Neutron radiation damage in zirconium and its alloys

There has been much research and speculation recently on the nature of radiation induced defects in zirconium and its alloys, and in particular on the absence of voids at high fluences and temperatures in the range 0.3 to 0.5 T _m (T _m is the absolute melting temperature). Wolfenden and Farrell¹ have reviewed the evidence and suggest that α-Zr has so far resisted void formation during neutron irradiation because of: (a) the absence of a dislocation (loop or tangle) structure and/or (b) a low insoluble gas (e.g. helium) content.     

The effect of porosity on the laser induced damage threshold of TiO2 and ZrO2 single layer films

Monolayer ZrO₂ and TiO₂ films were prepared on BK7 glass by physical vapor deposition (PVD) and were subsequently annealed for 1 h at 300 °C. By using the transmission spectra of two samples and the envelope method, the refractive index dispersion and extinction coefficients have been calculated. Laser induced damage threshold (LIDT) measurement shows that despite slight differences between the extinction coefficients of the two samples, the LIDT parameter of the ZrO₂ film is greater than that of the TiO₂ film. This fact leads us to consider thermal conductivity as an important parameter for interpreting the LIDT difference. According to our theoretical analysis, as a consequence of increase in the number of thermal barriers along poorer film, its thermal conductivity, and hence LIDT, decreased, which is in agreement with our experimental results. The measured porosity of the two samples shows higher porosity for TiO₂ single layer, which is in agreement with atomic force (AFM) images. The gradual and smooth damage morphology of ZrO₂ observed in optical images implies higher thermal conductivity than TiO₂.     

DNA aggregation and cleavage in CGE induced by high electric field in aqueous solution accompanying electrokinetic sample injection

The phenomenon of peak area decrease due to high injection voltage (V_inj, e.g. 10–30 kV, 200–600 V/cm in the 50 cm capillary) was found in the analysis of very dilute DNA fragments (<0.2 mg/L) by using high‐sensitive electrokinetic supercharging‐CGE. The possibility of DNA cleavage in aqueous solution was suggested, in addition to the aggregation phenomenon that is already known. The analysis of intentionally voltage‐affected fragments (at 200 V/cm) also showed decreased peak areas depending on the time of the voltage being applied. Computer simulation suggested that a high electric field (a few kV/cm or more) could be generated partly between the electrode and the capillary end during electrokinetic injection (EKI) process. After thorough experimental verification, it was found that the factors affecting the damage during EKI were the magnitude of electric field, the distance between tips of electrode and capillary (D_e/c), sample concentration and traveling time during EKI in sample vials. Furthermore, these factors are correlating with each other. A low conductivity of diluted sample would cause a high electric field (over a few hundred volts per centimeter), while the longer D_e/c results in a longer traveling time during EKI, which may cause a larger degree of damage (aggregation and cleavage) on the DNA fragments. As an important practical implication of this study, when the dilute DNA fragments (sub mg/L) are to be analyzed by CGE using EKI, injection voltage should be kept as low as possible.