Imaging and Downstaging Bladder Cancer with the 177Lu-Labeled Bioorthogonal Nanoprobe.

Efforts on bladder cancer treatment have been shifting from extensive surgery to organ preservation in the past decade. To this end, we herein develop a multifunctional nanoagent for bladder cancer downstaging and bladder-preserving therapy by integrating mucosa penetration, reduced off-target effects, and internal irradiation therapy into a nanodrug. Specifically, an iron oxide nanoparticle was used as a carrier that was coated with hyaluronic acid (HA) for facilitating mucosa penetration. Dibenzocyclooctyne (DBCO) was introduced into the HA coating layer to react through bioorthogonal reaction with azide as an artificial receptor of bladder cancer cells, to improve the cellular internalization of the nanoprobe labeled with 177Lu. Through magnetic resonance imaging, the targeted imaging of both nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) was realized after intravesical instillation of the multifunctional probe, both NMIBC and MIBC were found downstaged, and the metastasis was inhibited, which demonstrates the potential of the multifunctional nanoprobe for bladder preservation in bladder cancer treatment.

Reversing Acute Kidney Injury through Coordinated Interplay of Anti-Inflammation and Iron Supplementation.

Acute kidney injury (AKI) induced by ischemia reperfusion is closely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD+ ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, herein, an ultrasmall Fe3 O4 nanoparticle is used as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD+ . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe3 O4 nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD+ precursor into renal cells through nicotinamide riboside kinase 1 on the cell membrane. It is demonstrated that NMN-loaded Fe3 O4 nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicate that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previous strategies centering on anti-ROS (reactive oxygen species), anti-inflammation, or even iron elimination.

Exploring atherosclerosis imaging with contrast-enhanced MRI using PEGylated ultrasmall iron oxide nanoparticles.

Plaque rupture is a critical concern due to its potential for severe outcomes such as cerebral infarction and myocardial infarction, underscoring the urgency of noninvasive early diagnosis. Magnetic resonance imaging (MRI) has gained prominence in plaque imaging, leveraging its noninvasiveness, high spatial resolution, and lack of ionizing radiation. Ultrasmall iron oxides, when modified with polyethylene glycol, exhibit prolonged blood circulation and passive targeting toward plaque sites, rendering them conducive for MRI. In this study, we synthesized ultrasmall iron oxide nanoparticles of approximately 3 nm via high-temperature thermal decomposition. Subsequent surface modification facilitated the creation of a dual-modality magnetic resonance/fluorescence probe. Upon intravenous administration of the probes, MRI assessment of atherosclerotic plaques and diagnostic evaluation were conducted. The application of Flash-3D sequence imaging revealed vascular constriction at lesion sites, accompanied by a gradual signal amplification postprobe injection. T1-weighted imaging of the carotid artery unveiled a progressive signal ratio increase between plaques and controls within 72 h post-administration. Fluorescence imaging of isolated carotid arteries exhibited incremental lesion-to-control signal ratios. Additionally, T1 imaging of the aorta demonstrated an evolving signal enhancement over 48 h. Therefore, the ultrasmall iron oxide nanoparticles hold immense promise for early and noninvasive diagnosis of plaques, providing an avenue for dynamic evaluation over an extended time frame.

Energy investigation of effects of O on mechanical properties of NiAl intermetallics.

We have investigated effects of O on mechanical properties of NiAl by calculating the cleavage energy (γ(C)) and the unstable stacking fault energy (γ(us)) using a first-principles method. O is shown to reduce γ(C)/γ(us) for the [001](110) and [100](001) slip systems, indicating that the presence of O should be associated with the ductility reduction of NiAl. Further, γ(C)/γ(us) of the NiAl-O system can be increased by Cr, suggesting the possibility to suppress the negative effect of O via alloying elements.

Bonding characteristics in NiAl intermetallics with O impurity: a first-principles computational tensile test.

We have performed a first-principles computational tensile test on NiAl intermetallics with O impurity along the [001] crystalline direction on the (110) plane to investigate the tensile strength and the bonding characteristics of the NiAl-O system. We show that the ideal tensile strength is largely reduced due to the presence of O impurity in comparison with pure NiAl. The investigations of the atomic configuration and bond-length evolution show that O prefers to bond with Al, forming an O-Al cluster finally with the break of O-Ni bonds. The O-Ni bonds are demonstrated to be weaker than the O-Al bonds, and the reduced tensile strength originates from such weaker O-Ni bonds. A void-like structure forms after the break of the O-Ni and some Ni-Al bonds. Such a void-like structure can act as the initial nucleation or the propagation path of the crack, and thus produce large effects on the mechanical properties of NiAl.

Formation of a coplanar O-Al bonding cluster: the effect of O impurity on a Σ = 5 NiAl grain boundary from first-principles.

The site occupancy, structure, and bonding properties of O in an NiAl grain boundary (GB) have been investigated by employing a first-principles total energy method based on density functional theory with the generalized gradient approximation and ultrasoft pseudopotential. The Σ5(310)/[001] tilt GB of NiAl has been chosen because (i) the Σ = 5 GB has been observed to be a higher fraction in NiAl experimentally, and (ii) the Σ5(310)/[001] is energetically favorable in comparison with the Σ5(210)/[001]. The NiAl GB is shown to favor the O segregation with a segregation energy of -1.75 eV, indicating that most of the O impurity will distribute in the NiAl GB thermodynamically. Moreover, O is shown to prefer occupying the interstitial sites rather than the substitutional sites in the GB according to the calculated formation energies. The O-Al bond is energetically favorable as compared with the O-Ni bond due to different electronegativity of Al and Ni in reference to O. Charge distribution and the density of states further indicate the intrinsic bonding properties of O-Al that contain obvious covalent characteristics. It is interesting to find that O is coplanar with the surrounding Al atoms in both interstitial and substitutional cases with lower formation energies, forming stronger coplanar O-Al bonding clusters. Such stronger bonding clusters in the GB can embrittle the NiAl intermetallics and thus are not beneficial to the plasticity of NiAl. Our results will provide a useful reference for improving the mechanical properties and for understanding the oxidation effect of the NiAl intermetallics.

Mapping and initial analysis of human subtelomeric sequence assemblies.

Physical mapping data were combined with public draft and finished sequences to derive subtelomeric sequence assemblies for each of the 41 genetically distinct human telomere regions. Sequence gaps that remain on the reference telomeres are generally small,well-defined,and for the most part,restricted to regions directly adjacent to the terminal (TTAGGG)n tract. Of the 20.66 Mb of subtelomeric DNA analyzed, 3.01 Mb are subtelomeric repeat sequences (Srpt),and an additional 2.11 Mb are segmental duplications. The subtelomeric sequence assemblies are enriched >25-fold in short,internal (TTAGGG)n-like sequences relative to the rest of the genome; a total of 114 (TTAGGG)n-like islands were found,55 within Srpt regions,35 within one-copy regions,11 at one-copy/Srpt or Srpt/segmental duplication boundaries,and 13 at the telomeric ends of assemblies. Transcripts were annotated in each assembly,noting their mapping coordinates relative to their respective telomere and whether they originate in duplicated DNA or single-copy DNA. A total of 697 transcripts were found in 15.53 Mb of one-copy DNA,76 transcripts in 2.11 Mb of segmentally duplicated DNA,and 168 transcripts in 3.01 Mb of Srpt sequence. This overall transcript density is similar (within approximately 10%) to that found genome-wide. Zinc finger-containing genes and olfactory receptor genes are duplicated within and between multiple telomere regions.