A Numerical Study of the Mechanical Behavior of Jointed Soft Rocks under Triaxial Loading Using a Bonded Particle Model.

In order to master the strength and deformation characteristics, including the macro-micro failure mechanism of soft rock samples with penetrating joints under triaxial loading, a series of numerical triaxial tests have been carried out. The strength and deformation characteristics, failure modes, crack propagation, distribution of force chains, and the influences of joint dip angles and confining pressures have been analyzed and compared with the laboratory test results. The results show that (1) the residual strength ratio of jointed rock samples generally increases first and then decreases with the increase in joint dip angles under the same confining pressure and reaches the maximum value around 23-24°.

Partial Magneto-Endosomalysis for Cytosolic Delivery of Antibodies.

Modulation of protein functions and interactions is the most direct and effective means to intervene in cellular processes and pathogenesis. The majority of the critical intracellular signaling pathways, however, are considered undruggable using small molecules. In this regard, antibodies are superior in structural and functional diversity and are significantly easier to raise compared to the screening of small molecules.

Magneto-Endosomalytic Therapy for Cancer.

A remarkably simple yet effective mode of cancer treatment is reported by repurposing clinically approved magnetic nanoparticles (MNPs). Intracellular nanoparticle self-assembly directed by static parallel magnetic fields leads to cell death in targeted tissues while leaving other cells and organs intact. This simple concept opens a new avenue to treat cancer, capitalizing on nanosciences and the nanoparticle (NP) design principles accumulated in the past decades.

Cytosolic delivery of proteins by cholesterol tagging.

Protein-based imaging agents and therapeutics are superior in structural and functional diversity compared to small molecules and are much easier to design or screen. Antibodies or antibody fragments can be easily raised against virtually any target. Despite these fundamental advantages, the power and impact of protein-based agents are substantially undermined, only acting on a limited number of extracellular targets because macrobiomolecules cannot spontaneously cross the cell membrane.

Combining Qdot Nanotechnology and DNA Nanotechnology for Sensitive Single-Cell Imaging.

Immunohistochemistry (IHC) can provide detailed information about protein expression within the cell microenvironment and is one of the most common techniques in biology and medicine due to the broad availability of highly specific antibodies and well-established bioconjugation methods for modification of these antibodies with chromogens and fluorophores. Despite recent advances in this field, it remains challenging to simultaneously achieve high multiplexing, sensitivity, and throughput in single-cell profiling experiments. Here, the combination of two powerful technologies is reported, quantum dot and signal amplification by exchange reaction (QD-SABER), for sensitive and multiplexed imaging of endogenous proteins.

Triplex DNA Nanoswitch for pH-Sensitive Release of Multiple Cancer Drugs.

A DNA-based stimulus-responsive drug delivery system for synergetic cancer therapy has been developed. The system is built on a triplex-DNA nanoswitch capable of precisely responding to pH variations in the range of ∼5.0-7.

Publisher Correction: A ribonucleoprotein octamer for targeted siRNA delivery.

In the version of this Article originally published, in Fig. 3b, middle row, the units 'nM' were incorrect and should have been 'min'. And, in Fig.

A ribonucleoprotein octamer for targeted siRNA delivery.

Hurdles in cell-specific delivery of small interfering RNA (siRNA) in vivo hinder the clinical translation of RNA interference (RNAi). A fundamental problem concerns conflicting requirements for the design of the delivery vehicles: cationic materials facilitate cargo condensation and endosomolysis, yet hinder in vivo targeting and colloidal stability. Here, we describe a self-assembled, compact (~30 nm) and biocompatible ribonucleoprotein-octamer nanoparticle that achieves endosomal destabilization and targeted delivery.

Membrane-Penetrating Carbon Quantum Dots for Imaging Nucleic Acid Structures in Live Organisms.

The dynamics of DNA and RNA structures in live cells are important for understanding cell behaviors, such as transcription activity, protein expression, cell apoptosis, and hereditary disease, but are challenging to monitor in live organisms in real time. The difficulty is largely due to the lack of photostable imaging probes that can distinguish between DNA and RNA, and more importantly, are capable of crossing multiple membrane barriers ranging from the cell/organelle to the tissue/organ level. We report the discovery of a cationic carbon quantum dot (cQD) probe that emits spectrally distinguishable fluorescence upon binding with double-stranded DNA and single-stranded RNA in live cells, thereby enabling real-time monitoring of DNA and RNA localization and motion.

Quantum dots and mouse strain influence house dust mite-induced allergic airway disease.

Quantum dot nanoparticles (QDs) are engineered nanomaterials (ENMs) that have utility in many industries due to unique optical properties not available in small molecules or bulk materials. QD-induced acute lung inflammation and toxicity in rodent models raise concerns about potential human health risks. Recent studies have also shown that some ENMs can exacerbate allergic airway disease (AAD).

Quantum dot induced acute changes in lung mechanics are mouse strain dependent.

Introduction: Concerns have been raised regarding occupational exposure to engineered nanomaterials (ENMs). Potential impacts on lung function from inhalation exposures are of concern as the lung is a sensitive ENM target in animals. Epidemiological data suggest that occupational exposure to ENMs may impact respiratory and cardiovascular health.

Scalable Production of Therapeutic Protein Nanoparticles Using Flash Nanoprecipitation.

Flash nanoprecipitation (FNP) by fast mixing of drug-containing organic solvent and water in a microchamber is a powerful and scalable technology to produce solid drug nanoparticles with high payload. The embedded therapeutic drugs, however, are largely limited to hydrophobic small molecules. By transferring proteins into organic solvent via hydrophobic ion pairing, the scope of FNP applications is expanded.

Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation.

Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage.

Lipid Stabilized Solid Drug Nanoparticles for Targeted Chemotherapy.

Nanoparticle-based chemotherapeutics have gained widespread interest in medicine due to their tunable pharmacokinetics and pharmacodynamics. Various drug delivery vehicles have been developed including polymer, liposome nanoparticles, and some of them have already made clinical impacts. Despite these advances, drug payload of these formulations is limited (typically <10%).

A universal strategy for the one-pot synthesis of SERS tags.

Surface-enhanced Raman scattering (SERS) tags have attracted tremendous attention in diverse fields owing to their outstanding sensitivity and multiplexing capability. However, the selection of Raman dyes that can be immobilized onto metal nanoparticles is very limited, because certain chemical groups are needed in the dye molecules to interact either with the metal surface or through some intermediate layers. Here, we report a simple, rapid, and robust platform methodology for the one-pot preparation of Raman nanoprobes without the constraints of Raman dye chemical structures.

Cross-Platform Cancer Cell Identification Using Telomerase-Specific Spherical Nucleic Acids.

Distinguishing tumor cells from normal cells holds the key to precision diagnosis and effective intervention of cancers. The fundamental difficulties, however, are the heterogeneity of tumor cells and the lack of truly specific and ideally universal cancer biomarkers. Here, we report a concept of tumor cell detection, bypassing the specific genotypic and phenotypic features of different tumor cell types and directly going toward the hallmark of cancer, uncontrollable growth.

Noncovalent tagging of siRNA with steroids for transmembrane delivery.

Short interfering RNA (siRNA) has broad applications in biology and medicine, and holds tremendous potential to become a new class of therapeutics for many diseases. As a highly anionic macrobiomolecule, its cytosolic delivery, however, has been a major roadblock in translation. Here, we report the development of small, bifunctional chemical tags capable of transporting siRNA directly into the cytosol.

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning.

Dramatic enhancement of the detection limits of bioassays via ultrafast deposition of polydopamine.

The ability to detect biomarkers with ultrahigh sensitivity radically transformed biology and disease diagnosis. However, owing to incompatibilities with infrastructure in current biological and medical laboratories, recent innovations in analytical technology have not received broad adoption. Here, we report a simple, universal 'add-on' technology (dubbed EASE) that can be directly plugged into the routine practices of current research and clinical laboratories and that converts the ordinary sensitivities of common bioassays to extraordinary ones.

Engineering Single Nanopores on Gold Nanoplates by Tuning Crystal Screw Dislocation.

Compared with the large variety of solid gold nanostructures, synthetic approaches for their hollow counterparts are limited, largely confined to chemical and irradiation-based etching of preformed nanostructures. In particular, the preparation of through nanopore structures is extremely challenging. Here, a unique strategy for direct synthesis of gold nanopores in solution without the need for sacrificial templates or postsynthesis processing is reported.

Gradient Coating of Polydopamine via CDR.

Surfaces with gradient properties are of central importance for a number of chemical and biological processes. Here, we report rapid generation of a polydopamine (PDA) gradient on hydrophobic surfaces by a simple, low cost, and general technology, cyclic draining-replenishing (CDR). Due to the unique surface chemistry of PDA, it enables continuous and precise control of surface wettability and subsequent deposition of organic and inorganic compounds.

Eliminating Diffusion Limitations at the Solid-Liquid Interface for Rapid Polymer Deposition.

Polydopamine (PDA), a bioinspired polymer, has found diverse applications including biotechnology and energy research due to its unique properties for surface modification. In recent years, the reaction conditions for dopamine polymerization and thin film growth have been thoroughly examined and optimized. The fundamental problem of diffusion limitation at the solid-liquid interface that slows down PDA deposition, however, remains to be addressed.

Eliminating the Animal Species Constraints in Antibody Selection for Multicolor Immunoassays.

Molecular profiling on the single-cell level helps unveil the mystery of gene expression patterns in individual cells at subcellular resolution, enabling discovery of small but meaningful variations that are often overlooked at the population level. Similar to other immunoassays, the most common and economical protocols are developed by combining primary antibodies (1'Abs) and fluorophore-labeled secondary antibodies (2'Abs). The selection of 1' and 2' Abs, however, has been limited by the availability of animal species, consequently resulting in low multiplexing capability.