Dual Functionality of 6-Methylthioguanine: Synergistic Effects Enhancing the Photolability of DNA Nucleobases.

A small chemical modification of the nucleobase structure can significantly enhance the photoactivity of DNA, which may incur DNA damage, thus holding promising applications in photochemotherapy treatment of cancers or pathogens. However, single substitution confers only limited phototoxicity to DNA. Herein, we combine femtosecond and nanosecond time-resolved spectroscopy with high-level calculations to disentangle the excited-state dynamics of 6-methylthioguanine (me6-TG) under variable wavelength UVA excitation (310-330 nm).

Fluorescence Quenching Dynamics of 2-Amino-7-methyl-1,8-naphthyridine in Abasic-Site-Containing DNA Duplexes for Nucleobase Recognition.

Dramatic fluorescence quenching of small heterocyclic ligands trapped in the abasic site (AP) of DNA has been implemented as an unprecedented strategy recognizing single-base mutations in sequence analysis of cancer genes. However, the key mechanisms governing selective nucleobase recognition remain to be disentangled. Herein, we perform fluorescence quenching dynamics studies for 2-amino-7-methyl-1,8-naphthyridine (AMND) in well-designed AP-containing DNA single/double strands.

Sequence-specific binding behavior of coralyne toward triplex DNA: An ultrafast time-resolved fluorescence spectroscopy study.

Triplex DNA structure has potential therapeutic application in inhibiting the expression of genes involved in cancer and other diseases. As a DNA-targeting antitumor and antibiotic drug, coralyne shows a remarkable binding propensity to triplex over canonical duplex and thus can modulate the stability of triplex structure, providing a prospective gene targeting strategy. Much less is known, however, about coralyne-binding interactions with triplex.

Layered double hydroxides for phosphorus recovery from lipid-rich waste anaerobic fermentation liquor.

This study aimed to extract orthophosphate (ortho-P) from lipid-rich waste AF liquor (AFL) by Mg/Al layered double hydroxides (Mg/Al LDHs) adsorption, evaluate the influence of carbonate and investigate adsorption mechanisms. The carbonate influence experiment using synthetic P-rich wastewater indicated that low carbonate level was favorable for P extraction by LDHs. And then, real AFL rich in volatile fatty acids (VFAs), carbonate and ortho-P was applied as adsorbate to explore the Mg/Al LDHs adsorption performance.

Free-Radical-Mediated Photoinduced Electron Transfer between 6-Thioguanine and Tryptophan Leading to DNA-Protein-Like Cross-Link.

The nucleobase analog 6-thioguanine (6-TG) has emerged as important immunosuppressant, anti-inflammatory, and anticancer drug in the past few decades, but its unique photosensitivity of absorbing strongly ultraviolet UVA light elicits photochemical hazards in many ways. The particularly intriguing yet unresolved question is whether the direct photoreaction of 6-TG can promote DNA-protein cross-links (DPCs) formation, which are large DNA adducts blocking DNA replication and physically impede DNA-related processes. Herein, by real-time observation of radical intermediates using time-resolved UV-vis absorption spectroscopy in conjunction with product analysis by HPLC-MS, we discover that UVA excitation of 6-TG triggers direct covalent cross-linking with tryptophan (TrpH) via an exquisite radical mechanism of electron transfer.

Ultrafast excited state dynamics and light-switching of [Ru(phen)(dppz)] in G-quadruplex DNA.

The triplet metal to ligand charge transfer (MLCT) luminescence of ruthenium (II) polypyridyl complexes offers attractive imaging properties, specifically towards the development of sensitive and structure-specific DNA probes. However, rapidly-deactivating dark state formation may compete with MLCT luminescence depending on different DNA structures. In this work, by combining femtosecond and nanosecond pump-probe spectroscopy, the MLCT relaxation dynamics of [Ru(phen)(dppz)] (phen = 1,10-phenanthroline, dppz = dipyridophenazine) in two iconic G-quadruplexes has been scrutinized.

One-electron oxidation of TAT-motif triplex DNA and the ensuing Hoogsteen hydrogen-bonding dissociation.

One-electron oxidation of adenine (A) leads initially to the formation of adenine radical cation (A). Subsequent deprotonation of A can provoke deoxyribonucleic acid (DNA) damage, which further causes senescence, cancer formation, and even cell death. However, compared with considerable reports on A reactions in free deoxyadenosine (dA) and duplex DNA, studies in non-B-form DNA that play critical biological roles are rare at present.

Sulfur-centered hemi-bond radicals as active intermediates in S-DNA phosphorothioate oxidation.

Phosphorothioate (PS) modifications naturally appear in bacteria and archaea genome and are widely used as antisense strategy in gene therapy. But the chemical effects of PS introduction as a redox active site into DNA (S-DNA) is still poorly understood. Herein, we perform time-resolved spectroscopy to examine the underlying mechanisms and dynamics of the PS oxidation by potent radicals in free model, in dinucleotide, and in S-oligomer.

Preferential Binding of π-Ligand Porphyrin Targeting 5'-5' Stacking Interface of Human Telomeric RNA G-Quadruplex Dimer.

Human telomeric RNA (TERRA) containing thousands of G-rich repeats has the propensity to form parallel-stranded G-quadruplexes. The emerging crucial roles of TERRA G-quadruplexes in RNA biology fuel increasing attention for studying anticancer ligand binding with such structures, which, however, remains scarce. Here we utilized multiple steady-state and time-resolved spectroscopy analyses in conjunction with NMR methods and investigated thoroughly the binding behavior of TMPyP4 to a TERRA G-quadruplex dimer formed by the 10-nucleotide sequence r(GGGUUAGGGU).

Degradation of Cytosine Radical Cations in 2'-Deoxycytidine and in i-Motif DNA: Hydrogen-Bonding Guided Pathways.

Radical cations of nucleobases are key intermediates causing genome mutation, among which cytosine C is of growing importance because the ensuing cytosine oxidation causes GC → AT transversions in DNA replication. Although the chemistry and biology of steady-state C oxidation products have been characterized, time-resolved study of initial degradation pathways of C is still at the preliminary stage. Herein, we choose i-motif, a unique C-quadruplex structure composed of hemiprotonated base pairs C(H):C, to examine C degradation in a DNA surrounding without interference of G bases.

Binding Interactions of Zinc Cationic Porphyrin with Duplex DNA: From B-DNA to Z-DNA.

Recognition of unusual left-handed Z-DNA by specific binding of small molecules is crucial for understanding biological functions in which this particular structure participates. Recent investigations indicate that zinc cationic porphyrin (ZnTMPyP4) is promising as a probe for recognizing Z-DNA due to its characteristic chiroptical properties upon binding with Z-DNA. However, binding mechanisms of the ZnTMPyP4/Z-DNA complex remain unclear.

Interaction between G-Quadruplex and Zinc Cationic Porphyrin: The Role of the Axial Water.

The interaction of ligands with G-quadruplexes has attracted considerable attention due to its importance in molecular recognition and anticancer drugs design. Here, we utilize triplet excited state as a sensitive reporter to study the binding interaction of zinc cationic porphyrin (ZnTMPyP4) with three G-quadruplexes, AG(TAG), (GTG)2, and (TGT)4. By monitoring the triplet decay dynamics of ZnTMPyP4 with transient absorption spectroscopy, the coexisted binding modes via π-π stacking of porphyrin macrocycle and the G-quartets are allowed to be identified quantitatively, which involve intercalation (25% and 36%) versus end-stacking (75% and 64%) for AG(TAG) and (GTG)2, and end-stacking (23%) versus partial intercalation (77%) for (TGT)4.

Porphyrin Bound to i-Motifs: Intercalation versus External Groove Binding.

G-rich and C-rich DNA can fold into the tetrastranded helical structures G quadruplex or C quadruplex (i-motif), which are considered to be specific drug targets for cancer therapy. A large number of small molecules (so-called ligands), which can bind and modulate the stability of G quadruplex structures, have been widely examined. Much less is known, however, about the ligand binding interactions with the C quadruplex (i-motif).

Impurity Sub-Band in Heavily Cu-Doped InAs Nanocrystal Quantum Dots Detected by Ultrafast Transient Absorption.

The effect of Cu impurities on the absorption cross section, the rate of hot exction thermalization, and on exciton recombination processes in InAs quantum dots was studied by femtosecond transient absorption. Our findings reveal dynamic spectral effects of an emergent impurity sub-band near the bottom of the conduction band. Previously hypothesized to explain static photophysical properties of this system, its presence is shown to shorten hot carrier relaxation.

Three-pulse femtosecond spectroscopy of PbSe nanocrystals: 1S bleach nonlinearity and sub-band-edge excited-state absorption assignment.

Above band-edge photoexcitation of PbSe nanocrystals induces strong below band gap absorption as well as a multiphased buildup of bleaching in the 1Se1Sh transition. The amplitudes and kinetics of these features deviate from expectations based on biexciton shifts and state filling, which are the mechanisms usually evoked to explain them. To clarify these discrepancies, the same transitions are investigated here by double-pump-probe spectroscopy.

Long-Term Outcomes of Simultaneous Skin and Bowel Flaps for Esophageal Reconstruction.

Esophageal reconstruction can be performed with skin or bowel flaps. The choice of flap remains controversial, as the long-term outcomes of skin flaps cannot always be assessed in patients with limited life expectancies due to advanced malignancy, unlike the pediatric and benign cases which have had esophageal reconstruction using bowel flaps. We report the long-term clinical and histopathological outcomes in a series of 45 cases repaired with combined skin and bowel flaps.

Intramural metastases of rectum from carcinosarcoma (malignant müllerian mixed tumor) of uterine cervix.

A 25-year-old woman had carcinosarcoma of uterine cervix after definitive treatment. One year later, local recurrent disease was found in the right posterior pelvis on FDG PET/CT. FDG PET/CT also disclosed an incidental intramural hypermetabolic lesion in the rectum, which seemed separate from the right pelvic lesion on contrast-enhanced CT.

Parotid gland metastasis from squamous cell carcinoma of esophagus detected by FDG PET/CT.

A 55-year-old man was diagnosed with squamous cell carcinoma in the middle thoracic esophagus. The FDG PET/CT revealed an incidental strong FDG-avid finding (SUVmax, 11) in the right parotid gland, which was subsequently confirmed as metastasis from the squamous cell carcinoma of esophagus via surgery. The current case adds another differential diagnosis of parotid FDG-avid lesion to the existing literature.

Ultrafast formation of the benzoic acid triplet upon ultraviolet photolysis and its sequential photodissociation in solution.

Time-resolved infrared (TR-IR) absorption spectroscopy in both the femtosecond and nanosecond time domain has been applied to examine the photolysis of benzoic acid in acetonitrile solution following either 267 nm or 193 nm excitation. By combining the ultrafast and nanosecond TR-IR measurements, both the excited states and the photofragments have been detected and key mechanistic insights were obtained. We show that the solvent interaction modifies the excited state relaxation pathways and thus the population dynamics, leading to different photolysis behavior in solution from that observed in the gas phase.

Primary pulmonary epithelioid angiosarcoma presenting as a solitary pulmonary nodule on image.

Primary angiosarcoma of lung is a rare condition. Only about 20 cases have appeared in English published reports so far. Its rarity and consequent low index of suspicion makes clinical diagnosis difficult.

Synchronous squamous cell carcinomas of the esophagus and renal pelvis.

A 55-year-old man was incidentally diagnosed with a superficial squamous cell carcinoma of esophagus. However, the systemic survey with FDG PET/CT revealed a picture of more advanced disease because of the regional lymph node metastases and a suspected distal metastasis in the left renal pelvis, which was somewhat strange for a small superficial esophageal cancer. Subsequently, the renal pelvic lesion was confirmed as squamous cell carcinoma.