Synergistic Regulation of Bidirectional Conversion of LiPSs and LiS Using Anthraquinone as a Redox Mediator.

Lithium-sulfur (Li-S) batteries are strong contenders as energy storage options in the next-generation, primarily because of their potential for delivering high energy densities. Nonetheless, their widespread commercialization faces several obstacles, including sluggish sulfur redox kinetics, the insulating properties of the LiS discharge product, and significant reaction energy barriers. In this work, anthraquinone (AQ) was introduced as a redox mediator and incorporated onto Co-doped carbon materials through π-π interactions.

Unfolding rates of 1:1 and 2:1 complex of CX-5461 and c- promoter G-quadruplexes revealed by single-molecule force spectroscopy.

CX-5461, also known as pidnarulex, is a strong G4 stabilizer and has received FDA fast-track designation for BRCA1- and BRCA2- mutated cancers. However, quantitative measurements of the unfolding rates of CX-5461-G4 complexes which are important for the regulation function of G4s, remain lacking. Here, we employ single-molecule magnetic tweezers to measure the unfolding force distributions of c- G4s in the presence of different concentrations of CX-5461.

Distinguishing G-Quadruplexes Stabilizer and Chaperone for c- Promoter G-Quadruplexes through Single-Molecule Manipulation.

G-quadruplex (G4) selective stabilizing ligands can regulate c- gene expression, but the kinetic basis remains unclear. Determining the effects of ligands on c- promoter G4s' folding/unfolding kinetics is challenging due to the polymorphic nature of G4s and the high energy barrier to unfold c- promoter G4s. Here, we used single-molecule magnetic tweezers to manipulate a duplex hairpin containing a c- promoter sequence to mimic the transiently denatured duplex during transcription.

A TeZla micromixer for interrogating the early and broad folding landscape of G-quadruplex via multistage velocity descending.

Biomacromolecular folding kinetics involves fast folding events and broad timescales. Current techniques face limitations in either the required time resolution or the observation window. In this study, we developed the TeZla micromixer, integrating Tesla and Zigzag microstructures with a multistage velocity descending strategy.

Nonselective Intercalation of G-Quadruplex-Targeting Ligands into Double-Stranded DNA Quantified by Single-Molecule Stretching.

Most G-quadruplex (G4)-targeting ligands reported so far contain planar heteroaromatic groups and can intercalate into adjacent base pairs of double-stranded DNA (dsDNA). However, quantitative data on the binding number γ (ligands/bp) of G4 ligands that intercalate into long dsDNA remain lacking, which are essential for understanding the selectivity of G4 ligands. Here, using a single-molecule stretching assay based on the lengthening of dsDNA, we analyzed the dissociation constants and the binding number of eight most commonly used G4 ligands that intercalate into dsDNA.

Force-Dependent Intercalative Bulky DNA Adduct Formation Detected by Single-Molecule Stretching.

Quantitatively analyzing the binding topology and reactivity is essential for understanding the cytotoxic or tumorigenic activities of bulky DNA adducts formed by chemotherapeutic drugs or carcinogens. Biochemical methods require purification of DNA and discontinuous steps to digest or label the adducts and thus have difficulties in identifying the binding topology and are not suitable for detecting unstable adducts. Herein, we used a single-molecule stretching assay to characterize the number of intercalative adducts, the formation kinetics, and the mechanical properties of intercalative DNA adducts based on measuring adduct-induced DNA elongation.

Characterization of G-Quadruplexes Folding/Unfolding Dynamics and Interactions with Proteins from Single-Molecule Force Spectroscopy.

G-quadruplexes (G4s) are stable secondary nucleic acid structures that play crucial roles in many fundamental biological processes. The folding/unfolding dynamics of G4 structures are associated with the replication and transcription regulation functions of G4s. However, many DNA G4 sequences can adopt a variety of topologies and have complex folding/unfolding dynamics.

Mechanical diversity and folding intermediates of parallel-stranded G-quadruplexes with a bulge.

A significant number of sequences in the human genome form noncanonical G-quadruplexes (G4s) with bulges or a guanine vacancy. Here, we systematically characterized the mechanical stability of parallel-stranded G4s with a one to seven nucleotides bulge at various positions. Our results show that G4-forming sequences with a bulge form multiple conformations, including fully-folded G4 with high mechanical stability (unfolding forces > 40 pN), partially-folded intermediates (unfolding forces < 40 pN).

Using Magnetic Tweezers to Unravel the Mechanism of the G-quadruplex Binding and Unwinding Activities of DHX36 Helicase.

Single-molecule manipulation methods are useful techniques to probe the interactions of proteins and nucleic acid structures. Here, we describe the magnetic tweezers-based single-molecule investigation of the binding of helicases to G-quadruplex structures and their ATP-dependent unwinding activity, using DHX36 (also known as RHAU and G4R1) helicase and a DNA G-quadruplex structure for an example. We specifically emphasize on the principle and method to probe the interactions between DHX36 and the DNA G-quadruplex in different intermediate states during an ATPase cycle of DHX36, based on detecting the DHX36-induced changes in the lifetime of the DNA G-quadruplex under tension.

Single-Molecule Mechanical Unfolding of AT-Rich Chromosomal Fragile Site DNA Hairpins: Resolving the Thermodynamic and Kinetic Effects of a Single G-T Mismatch.

Chromosomal fragile sites (CFSs) contain AT-rich sequences that tend to form hairpins on lagging strands in DNA replication, making them hotspots for chromosomal rearrangements in cancers. Here, we investigate the structural stability of the AT-rich CFS DNA hairpins with a single non-AT base pair using magnetic tweezers. Strikingly, a single G-T mismatched base pair in the short CFS DNA hairpin gives a 38.

High Mechanical Stability and Slow Unfolding Rates Are Prevalent in Parallel-Stranded DNA G-Quadruplexes.

Guanine-rich repeat sequences are known to adopt diverse G-quadruplex (G4) topologies. Determining the unfolding rates of individual G4 species is challenging due to the coexistence of multiple G4 conformations in a solution. Here, using single-molecule magnetic tweezers, we systematically measured the unfolding force distributions of 4 oncogene promoter G4s, 12 model sequences with two 1-nucleotide (nt) thymine loops that predominantly adopt parallel-stranded G4 structures, and 6 sequences forming multiple G4 structures.

Oxygen-Challenge Blood Oxygen Level-Dependent Magnetic Resonance Imaging for Evaluation of Early Change of Hepatocellular Carcinoma to Chemoembolization: A Feasibility Study.

Rationale And Objectives: To investigate the feasibility of oxygen-challenge blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) at 3T for evaluating the early change of blood oxygenation before and after transcatheter arterial embolization (TACE) in patients with hepatocellular carcinoma (HCC).

Materials And Methods: Thirty HCC patients with cirrhosis (HCC group, n = 30) and 30 healthy volunteers (control group, n = 30) were included in this study. Patients in the HCC group underwent BOLD before and 1 month after TACE.

Noninvasive Differentiation of Obstructive Azoospermia and Nonobstructive Azoospermia Using Multimodel Diffusion Weighted Imaging.

Rationale And Objectives: To evaluate the diagnostic performance of parameters derived from multimodel diffusion weighted imaging (monoexponential, stretched-exponential diffusion weighted imaging and diffusion kurtosis imaging [DKI]) from noninvasive magnetic resonance imaging in distinguishing obstructive azoospermia (OA) from nonobstructive azoospermia (NOA).

Materials And Methods: Forty-six patients with azoospermia were prospectively enrolled and classified into two groups (21 OA patients and 25 NOA patients). The multimodel parameters of diffusion-weighted imaging (DWI; apparent diffusion coefficient [ADC], distributed diffusion coefficient [DDC], diffusion heterogeneity [α], diffusion kurtosis diffusivity [D], and diffusion kurtosis coefficient [K]) were derived.

Discrimination between benign and malignant testicular lesions using volumetric apparent diffusion coefficient histogram analysis.

Purpose: This study aimed to evaluate the role of volumetric apparent diffusion coefficient (ADC) histogram analysis in discriminating between benign and malignant testicular masses.

Methods: In this retrospective study, fifty-nine patients with 61 pathologically confirmed testicular masses were consecutively enrolled, including 18 benign lesions and 43 malignant lesions. All patients conducted preoperative magnetic resonance imaging (MRI) with diffusion-weighted imaging.

Sight and switch off: Nerve density visualization for interventions targeting nerves in prostate cancer.

Nerve density is associated with prostate cancer (PCa) aggressiveness and prognosis. Thus far, no visualization methods have been developed to assess nerve density of PCa in vivo. We compounded propranolol-conjugated superparamagnetic iron oxide nerve peptide nanoparticles (PSN NPs), which achieved the nerve density visualization of PCa with high sensitivity and high specificity, and facilitated assessment of nerve density and aggressiveness of PCa using magnetic resonance imaging and magnetic particle imaging.

Detecting the Formation Kinetics of Doxorubicin-DNA Interstrand Cross-link at the Single-Molecule Level and Clinically Relevant Concentrations of Doxorubicin.

Doxorubicin (DOX) ranks among the most effective anticancer agents. Increasing the formation of covalent DOX-DNA interstrand cross-links can improve the anticancer activity of DOX. However, due to the low stability of the DOX-DNA cross-links to heat and alkali, DOX can be extensively lost during isolation procedures of biochemical methods, thus reducing the apparent clinical relevance of this mechanism.

T2-Weighted Image-Based Radiomics Signature for Discriminating Between Seminomas and Nonseminoma.

To evaluate the performance of a T2-weighted image (T2WI)-based radiomics signature for differentiating between seminomas and nonseminomas. In this retrospective study, 39 patients with testicular germ-cell tumors (TGCTs) confirmed by radical orchiectomy were enrolled, including 19 cases of seminomas and 20 cases of nonseminomas. All patients underwent 3T magnetic resonance imaging (MRI) before radical orchiectomy.

Validation of SE-EPI-based T2 mapping for characterization of prostate cancer: a new method compared with the traditional CPMG method.

Purpose: We aim to compare the results of spin echo-echo planar imaging (SE-EPI)-based T2 mapping with those of the conventional Carr-Purcell-Meiboom-Gill (CPMG) method and to investigate the potential validity of SE-EPI-T2 mapping for the characterization of prostate cancer (PCa).

Methods: Our retrospective study included 42 PCa patients and 42 noncancer patients who underwent 3.0T MRI with b values ranging from 0 to 2000 s/mm and echo times (TEs) ranging from 32 to 100 ms before biopsies.

Multi-parametric MRI-based radiomics signature for discriminating between clinically significant and insignificant prostate cancer: Cross-validation of a machine learning method.

Purpose: To evaluate the performance of a multi-parametric MRI (mp-MRI)-based radiomics signature for discriminating between clinically significant prostate cancer (csPCa) and insignificant PCa (ciPCa).

Materials And Methods: Two hundred and eighty patients with pathology-proven PCa were enrolled and were randomly divided into training and test cohorts. Eight hundred and nineteen radiomics features were extracted from mp-MRI for each patient.

Folding/unfolding kinetics of G-quadruplexes upstream of the P1 promoter of the human oncogene.

The G-rich Pu39 region of the P1 promoter of the oncogene , an apoptosis regulator, can fold into multiple G-quadruplex (G4) structures. Bcl2-2345 and Bcl2-1245 are two major G4 species forming with high thermal stability and distinct topologies in the Pu39 region, but their folding/unfolding kinetics have not yet been investigated. Here, we used magnetic tweezers to measure the mechanical stability and the folding/unfolding kinetics of the Bcl2-2345 and Bcl2-1245 G4 structures.

The Mechanical Properties of RNA-DNA Hybrid Duplex Stretched by Magnetic Tweezers.

RNA can anneal to its DNA template to generate an RNA-DNA hybrid (RDH) duplex and a displaced DNA strand, termed R-loop. RDH duplex occupies up to 5% of the mammalian genome and plays important roles in many biological processes. The functions of RDH duplex are affected by its mechanical properties, including the elasticity and the conformation transitions.