High fidelity detection of miRNAs from complex physiological samples through electrochemical nanosensors empowered by proximity catalysis and magnetic separation.

Electrochemical detection of miRNA biomarkers in complex physiological samples holds great promise for accurate evaluation of tumor burden in the perioperative period, yet limited by reproducibility and bias issues. Here, nanosensors installed with hybrid probes that responsively release catalytic DNAzymes (G-quadruplexes/hemin) were developed to solve the fidelity challenge in an immobilization-free detection. miRNA targets triggered toehold-mediated strand displacement reactions on the sensor surface and resulted in amplified shedding of DNAzymes. Subsequently, the interference background was removed by Fe3O4 core-facilitated magnetic separation. Binding aptamers of the electrochemical reporter (dopamine) were tethered closely to the catalytic units for boosting H2O2-mediated oxidation through proximity catalysis. The one-to-many conversion by dual amplification from biological-chemical catalysis facilitated sufficient homogeneous sensing signals on electrodes. Thereby, the nanosensor exhibited a low detection limit (2.08 fM), and high reproducibility (relative standard deviation of 1.99%). Most importantly, smaller variations (RSD of 0.51-1.04%) of quantified miRNAs were observed for detection from cell lysates, multiplexed detection from unprocessed serum, and successful discrimination of small upregulations in lysates of tumor tissue samples. The nanosensor showed superior diagnostic performance with an area under curve (AUC) of 0.97 and 94% accuracy in classifying breast cancer patients and healthy donors. These findings demonstrated the synergy of signal amplification and interference removal in achieving high-fidelity miRNA detection for practical clinical applications.

STC2 Inhibits Hepatic Lipid Synthesis and Correlates with Intramuscular Fatty Acid Composition, Body Weight and Carcass Traits in Chickens.

Stanniocalcin 2 (STC2) is a secreted glycoprotein involved in multiple biological processes. To systemically study the biological role of STC2 in chickens, phylogenetic tree analysis and conservation analysis were conducted. Association analysis between variations in the STC2 gene and the economic traits of Gushi-Anka F2 was conducted. The tissue expression patterns of STC2 expression in different chicken tissues and liver at different stages were detected. The biological role of STC2 in chicken liver was investigated through overexpression and interfering methods in the LMH cell line. Correlation analyses between STC2 expression and lipid components were conducted. (1) The phylogenetic tree displayed that chicken STC2 is most closely related with Japanese quail and most distantly related with Xenopus tropicalis. STC2 has the same identical conserved motifs as other species. (2) rs9949205 (T > C) found in STC2 intron was highly significantly correlated with chicken body weight at 0, 2, 4, 6, 8, 10 and 12 weeks (p < 0.01). Extremely significant correlations of rs9949205 with semi-evisceration weight (SEW), evisceration weight (EW), breast muscle weight (BMW), leg muscle weight (LMW), liver weight and abdominal fat weight (AFW) were revealed (p < 0.01). Significant associations between rs9949205 and abdominal fat percentage, liver weight rate, breast muscle weight rate and leg muscle weight rate were also found (p < 0.05). Individuals with TT or TC genotypes had significantly lower abdominal fat percentage and liver weight rate compared to those with the CC genotype, while their body weight and other carcass traits were higher. (3) STC2 showed a high expression level in chicken liver tissue, which significantly increased with the progression of age (p < 0.05). STC2 was observed to inhibit the content of lipid droplets, triglycerides (TG) and cholesterol (TC), as well the expression level of genes related to lipid metabolism in LMH cells. (4) Correlation analysis showed that the STC2 gene was significantly correlated with 176 lipids in the breast muscle (p < 0.05) and mainly enriched in omega-3 and omega-6 unsaturated fatty acids. In conclusion, the STC2 gene in chicken might potentially play a crucial role in chicken growth and development, as well as liver lipid metabolism and muscle lipid deposition. This study provides a scientific foundation for further investigation into the regulatory mechanism of the STC2 gene on lipid metabolism and deposition in chicken liver.

miR-19b-3p regulated by estrogen controls lipid synthesis through targeting MSMO1 and ELOVL5 in LMH cells.

miR-19b-3p is reported to undertake various biological role, while its function and action mechanism in chicken hepatic lipid metabolism is unclear. Conservation analysis and tissue expression pattern of miR-19b-3p and its target gene were evaluated, respectively. Dual luciferase reporter system and Western blot technologies were adopted to validate miR-19b-3p target gene. Overexpression and knockdown assays were done to explore the biological functions of miR-19b-3p and target gene in Leghorn Male Hepatoma cell line (LMH). Regulatory approaches of estrogen on miR-19b-3p and target gene expressions are analyzed through site-directed mutation combined with estrogen receptors antagonist treatment assays. The results showed that chicken miR-19b-3p mature sequences are highly conserved among Capra hircus, Columba livia, Rattus norvegicus, Mus musculus, Cricetulus griseus, Danio rerio, Danio novaehollandiae, Orycodylus porosus, Crocodylus porosus, Gadus morhua, and widely expressed in lung, ovary, spleen, duodenum, kidney, heart, liver, leg muscle, and pectoral muscle tissues. miR-19b-3p could significantly increase intracellular triglyceride (TG) content and decrease intracellular cholesterol (TC) content via targeting methylsterol monooxygenase 1 (MSMO1) and elongase of very long chain fatty acids 5 (ELOVL5), which are highly conserved among species, in both mRNA and protein levels. Estrogen could inhibit miR-19b-3p expression, but directly promoted MSMO1 transcription via estrogen receptor α (ERα) and indirectly regulated ELOVL5 expression at the transcription level. Meanwhile, estrogen could also upregulate MSMO1 and ELOVL5 expression through inhibiting miR-19b-3p expression at the post-transcription level. Taken together, these results highlight the role and regulatory mechanism of miR-19b-3p in hepatic lipid metabolism in chicken, and might produce useful comparative information for human obesity studies and biomedical research.

Genomic Insights into Molecular Regulation Mechanisms of Intramuscular Fat Deposition in Chicken.

Intramuscular fat (IMF) plays an important role in the tenderness, water-holding capacity, and flavor of chicken meat, which directly affect meat quality. In recent years, regulatory mechanisms underlying IMF deposition and the development of effective molecular markers have been hot topics in poultry genetic breeding. Therefore, this review focuses on the current understanding of regulatory mechanisms underlying IMF deposition in chickens, which were identified by multiple genomic approaches, including genome-wide association studies, whole transcriptome sequencing, proteome sequencing, single-cell RNA sequencing (scRNA-seq), high-throughput chromosome conformation capture (HiC), DNA methylation sequencing, and m6A methylation sequencing. This review comprehensively and systematically describes genetic and epigenetic factors associated with IMF deposition, which provides a fundamental resource for biomarkers of IMF deposition and provides promising applications for genetic improvement of meat quality in chicken.

Catalytically proficient ceria nanodots supported on redox-active mesoporous hosts for treatment of inflammatory bowel disease via efficient ROS scavenging.

Ceria nanozyme-based ROS scavengers have shown great potential in the treatment of inflammatory bowel disease (IBD) through microenvironment regulation. However, the currently developed nanotherapeutics suffer from difficulties in concomitantly achieving small sizes and stable interparticle dispersion which is pivotal to sufficient oxygen vacancies facilitating electron transfer and oxygen storage in the dynamic cycling of Ce3+/Ce4+ redox pairs. Herein, a hybrid nanosystem consisting of ceria nanodots supported on redox-active mesoporous hosts was developed to address the challenge of ROS scavenging, in particular the efficient downregulation of the readily renewable, highly concentrated H2O2 species. Specifically, Ce4+ ions oxidized from Ce3+ in weakly basic solution were captured and reduced in time by the abundant catechols on the mesoporous polydopamine nanoparticles. This led to strong restriction of ceria growth (∼2.8 nm) in the ion precipitation process and efficient maintenance of the Ce3+/Ce4+ ratio at a high value of 1.59 which is 4.8 fold higher than that of homogeneously nucleated ceria nanoparticles. Through this design, the nanohybrid showed an attractive catalytic performance in scavenging multiple ROS species, particularly the fast and recyclable conversion of H2O2. Thereby, significant suppression of the inflammatory cytokine/chemokine secretion was achieved by inhibiting the activation of NF-κB signaling pathways (5.1 fold higher as compared to those of pristine ceria nanoparticles), upregulating the Nrf2 signaling pathway, and reducing the proportion of M1 macrophages at IBD sites. Therapeutic efficiency was also demonstrated by the effective repair of the intestinal mucosal barrier by recovering the tight junction integrity in vivo. This study sheds light on the employment of redox-active hosts to support ceria catalysts for advancing anti-inflammation applications by boosting ROS scavenging performance.

Flower-like Nanozyme with Highly Porous Carbon Matrix Induces Robust Oxidative Storm against Drug-Resistant Cancer.

Reactive oxygen species (ROS) generators are sparking breakthroughs in sensitization and treatment of therapy-resistant tumors, yet the efficacy is drastically compromised by limited substrate concentrations, short lifetimes of free radicals, and restricted oxidative damage. Herein, a flower-like nanozyme with highly permeable leaflets accommodating catalytic metal sites was developed to address the challenges by boosting substrate and product accessibility. In the formation of a zeolite imidazole framework, cobalt ions promoted catalytic polymerization and deposition of polydopamine. The polymers acted as a stiffener for preventing framework collapse and maneuvering pore reopening during carbonization. The cobalt single-atom/cluster sites in the highly porous matrix generated peroxidase/oxidase-like activities with high catalytic efficiency (Kcat/Km) up to 6 orders of magnitude greater than that of conventional nano-/biozymes. Thereby, a robust ROS storm induced by selective catalysis led to rapid accumulation of oxidative damage and failure of antioxidant and antiapoptotic defense synchronization in drug-resistant cancer cells. By synergy of a redox homeostasis disrupter co-delivered, a significantly high antitumor efficiency was realized in vivo. This work offers a route to kinetically favorable ROS generators for advancing the treatment of therapy-resistant tumors.

Dual factor coactivatable fluorescent nanosensor with boosted cytoplasmic biomarker accessibility toward selective tumor imaging.

Fluorescent nanosensor-based tumor imaging holds great promise in cancer diagnosis and treatment assistance, yet the signal contrast is heavily hampered by the unspecific/unwanted activation at microscopic regions with a highly restricted local abundance of biomarkers. Herein, we developed an activation boosting strategy by the integration and manipulation of dual-factor coactivation of sensing and lysosome escape facilitated the rise of cytosolic biomarker accessibility. By employing hybrid DNA probes on gold nanoquenchers, ATP sensing initiated conformation switch of the corresponding aptamer units triggered the exposure of a hidden toehold in a loop structure. Sequentially, miRNA-21 sensing was triggered by toehold-mediated strand displacement and detachment of the binding complexes. The application of lysosomotropic agent chloroquine at optimized time interval facilitated the release of nanosensors into the cytosol and a ∼10.5-fold increment of intracellular fluorescence in vitro, while coactivation improved the cancer-to-normal cell signal ratio by ∼5.9 times. The synergy effects led to a high tumor-to-normal tissue ratio value of ∼7.9 in the in vivo imaging results. This strategy establishes a new paradigm of fluorescent nanosensors for selective and specific tumor imaging.

Super-Large-Scale Hierarchically Porous Films Based on Self-Assembled Eye-Like Air Pores for High-Performance Daytime Radiative Cooling.

Metal-free polymer daytime radiative cooling coatings with hierarchical eye-like air pores are proposed and fabricated with a super-large-scale film-stretching method. The hierarchically porous film (HPF) can be further coated with polymethyl methacrylate (PMMA) micro-hemispheres, forming coated HPF (cHPF), which do not dramatically change the optical or thermal properties. The cHPF is slightly better with a lower solar absorptivity (2.4%) and a higher thermal emissivity over the atmospheric transparency window (90.1%). The low solar absorptivity is due to the strong scattering of the hierarchical eye-like air pores, while the molecular vibrations and the focusing effect of the PMMA micro-hemispheres contribute to the high emissivity. An average mid-day temperature reduction of 7.92 °C is achieved relative to the air temperature, and the average cooling power reaches 116.0 W m-2 , which are much better than the cooling performances of the commercial cooling cushion. During the day, the cHPF-covered simulated building is up to 6.47 and 4.84 °C cooler than the ambient and the white painted counterpart, respectively. The film is durable and resistant to chemical etching, and very promising to use globally, especially in warm and tropical regions.

4D dual-mode staring hyperspectral-depth imager for simultaneous spectral sensing and surface shape measurement.

A 4D dual-mode staring hyperspectral-depth imager (DSHI), which acquire reflectance spectra, fluorescence spectra, and 3D structural information by combining a staring hyperspectral scanner and a binocular line laser stereo vision system, is introduced. A 405 nm laser line generated by a focal laser line generation module is used for both fluorescence excitation and binocular stereo matching of the irradiated line region. Under the configuration, the two kinds of hyperspectral data collected by the hyperspectral scanner can be merged into the corresponding points in the 3D model, forming a dual-mode 4D model. The DSHI shows excellent performance with spectral resolution of 3 nm, depth accuracy of 26.2 µm. Sample experiments on a fluorescent figurine, real and plastic sunflowers and a clam are presented to demonstrate system's with potential within a broad range of applications such as, e.g., digital documentation, plant phenotyping, and biological analysis.

Polymer-based planar waveguide chirped Bragg grating for high-resolution tactile sensing.

A novel tactile sensor for two-dimensional force location measurements, based on polymer-based planar waveguide chirped Bragg gratings (PPCBGs) fabricated on sheet PMMA substrate, is presented. The planar waveguide and chirped Bragg grating are simultaneously generated using a KrF excimer laser and a phase mask covered by a quartz chrome mask. Location and magnitude of an applied force is measured by observing the change of the wavelength of a dip in the measured spectrum and a change in the reflectivity intensity. Experimental characterization indicates submillimeter spatial resolution of applied force in the range of 1-4 N with a sensitivity of 947.02 pm/mm.

Near-Field Radiative Heat Transfer Modulation with an Ultrahigh Dynamic Range through Mode Mismatching.

Modulating near-field radiative heat transfer (NFRHT) with a high dynamic range is challenging in nanoscale thermal science and engineering. Modulation depths [(maximum value - minimum value)/(maximum value + minimum value) × 100%] of ≈2% to ≈15.7% have been reported with matched modes, but breaking the constraint of mode matching theoretically allows for higher modulation depth. We demonstrate a modulation depth of ≈32.2% by a pair of graphene-covered SU8 heterostructures at a gap distance of ≈80 nm. Dissimilar Fermi levels tuned by bias voltages enable mismatched surface plasmon polaritons which improves the modulation. The modulation depth when switching from a matched mode to a mismatched mode is ≈4.4-fold compared to that when switching between matched modes. This work shows the importance of symmetry in polariton-mediated NFRHT and represents the largest modulation depth to date in a two-body system with fixed gap distance and temperature.

Strong Coupling between a Single Quantum Emitter and a Plasmonic Nanoantenna on a Metallic Film.

The strong coupling between single quantum emitters and resonant optical micro/nanocavities is beneficial for understanding light and matter interactions. Here, we propose a plasmonic nanoantenna placed on a metal film to achieve an ultra-high electric field enhancement in the nanogap and an ultra-small optical mode volume. The strong coupling between a single quantum dot (QD) and the designed structure is investigated in detail by both numerical simulations and theoretical calculations. When a single QD is inserted into the nanogap of the silver nanoantenna, the scattering spectra show a remarkably large splitting and anticrossing behavior of the vacuum Rabi splitting, which can be achieved in the scattering spectra by optimizing the nanoantenna thickness. Our work shows another way to enhance the light/matter interaction at a single quantum emitter limit, which can be useful for many nanophotonic and quantum applications.

Interfacially responsive electron transfer and matter conversion by polydopamine-mediated nanoplatforms for advancing disease theranostics.

Polydopamine (PDA) is an artificial melanin polymer that has been spotlighted due to its extraordinary optoelectronic characteristics and advance theranosctic applications in biomaterial fields. Moreover, interactions on the nano-bio interface interplay whereby substances exchange in response to endogenous or exogenous stimuli, and electron transfer driven by light, energy-level transitions, or electric field greatly affect the functional performance of PDA-modified nanoparticles. The full utilization of potential in PDA's interfacial activities, optoelectrical properties and related responsiveness is therefore an attractive means to construct advanced nanostructures for regulating biological processes and metabolic pathways. Herein, we strive to summarize recent advances in the construction of functional PDA-based nanomaterials with state-of-the-art architectures prepared for modulation of photoelectric sensing and redox reversibility, as well as manipulation of photo-activated therapeutics. Meanwhile, contributions of interfacial electron transfer and matter conversion are highlighted by discussing the structure-property-function relationships and the biological effects in their featured applications including disease theranostics, antibacterial activities, tissue repair, and combined therapy. Finally, the current challenges and future perspectives in this emerging research field will also be outlined. Recent advances on polydopamine-based nanotherapeutics with an emphasis on their interfacial activities, optoelectrical properties and related responsiveness are reviewed for providing insightful guidance to the rational design of integrated theranostic nanoplatforms with high performance in the biomedical fields. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Cobalt-loaded cherry core biochar composite as an effective heterogeneous persulfate catalyst for bisphenol A degradation.

Persulfate (PS)-based advanced oxidation processes have drawn tremendous attention for the degradation of recalcitrant pollutants, and cobalt composites are effective for PS activation to generate reactive species. In this study, composites of cobalt species loaded on cherry core-derived biochar (Co/C) were prepared with a one-step pyrolysis method. The Co/C catalyst was applied as a catalyst for PS activation to degrade bisphenol A (BPA). Factors influencing the degradation efficiency were examined, including the ratio of raw materials, Co/C and PS dosages, temperature, and solution pH. The Co/C catalyst prepared when the ratio of raw material was 1 : 1 (Co/C-50) could efficiently activate both peroxymonosulfate (PMS) and peroxydisulfate (PDS). When the initial concentration of BPA was 20 mg L-1, complete removal of BPA was achieved in the Co/C-50-PMS and Co/C-50-PDS systems within 8 min and 10 min, respectively. More than 70% of BPA could be mineralized in the Co/C-50-PS system. The free radical quenching experiments demonstrated that in the Co/C-50-PS system, the degradation of BPA was achieved through free radical, surface-bound free radical, and non-free radical pathways. The successful preparation of the Co/C-50-PS catalyst broadens the application of cobalt-based carbon materials in the activation of PS to remove organic pollutants.

Photothermally triggered melting and perfusion: responsive colloidosomes for cytosolic delivery of membrane-impermeable drugs in tumor therapy.

A cell membrane barrier which dominates the therapeutic efficacy and systemic side effects is a major bottleneck in the field of drug delivery. Herein, a therapeutic system capable of photothermally triggered on-demand and cytosolic delivery was achieved by polydopamine (PDA) nanoparticle-stabilized colloidosomes. An organic phase change material (PCM, saturated fatty acids) was employed as the lipid core for Pickering emulsification and drug encapsulation, and arginine was utilized as a linker to induce the directional interactions between nanoemulsion droplets and heterogeneously nucleated PDA nanoparticles. Moreover, the PDA particle stabilizers concomitantly mediated the grafting of hydrophilic polymer PEG to further improve dispersibility. The resultant colloidosomes after cooling possess lowered melting points and superior dispersion stability over 7 days. When irradiated with near-infrared light (808 nm), sequential processes of fatty acid melting and direct drug perfusion into the cytosol took place within 10 min. The employment of vorinostat (SAHA, histone deacetylase inhibitor) as a model membrane-impermeable drug resulted in remarkable enhancement of anti-cancer effects both in vitro (5.2 fold reduction in IC50) and in vivo (7.3 fold increase in tumor inhibition rate) with respect to the free drug. The remotely triggered transformable nanoplatform paves a new avenue of responsive and efficient cytosolic perfusion to overcome biological membrane barriers on the basis of colloidosomes.

Redox Host-Guest Nanosensors Installed with DNA Gatekeepers for Immobilization-Free and Ratiometric Electrochemical Detection of miRNA.

Electrochemical nanosensors by integrating functional nucleic acids and nanomaterials hold a great promise in the fast detection of biomarkers, yet the current systems possess limitations on the accessibility of target-probe and probe-electrode interactions and the repeatability of detection. Herein, a host-guest assembly strategy is developed to build redox nanosensors for an immobilization-free and ratiometric electrochemical detection system. Specifically, electroactive molecule (Em ) guests are loaded in porous hosts of polydopamine nanoparticles (MPDA) to act as dual-signal redox reporters. Hybrid DNA probes of G-quadruplex and a single-stranded anchor DNA are installed as gatekeepers for sealing the mesopores. Thereby, miRNA triggered Em release by strand displacement reactions and the homogeneous transportation of the hosts/guests to the electrode facilitate the generation of reference signal/response signal at different potentials. Concomitantly applied NIR irradiation boosts the electron transfer from MPDA to the electrode and results in a tenfold increase in the reference signal. Finally, the sensing system through the differential pulse voltammetry method achieves a highly repeatable detection (relative standard deviation 3.8%) of miRNA with a lower detection limit (362 × 10-15 m). This attractive system paves the way for rational designs of advanced electrochemical biosensors and smart diagnosis.

A highly stable, nanotube-enhanced, CMOS-MEMS thermal emitter for mid-IR gas sensing.

The gas sensor market is growing fast, driven by many socioeconomic and industrial factors. Mid-infrared (MIR) gas sensors offer excellent performance for an increasing number of sensing applications in healthcare, smart homes, and the automotive sector. Having access to low-cost, miniaturized, energy efficient light sources is of critical importance for the monolithic integration of MIR sensors. Here, we present an on-chip broadband thermal MIR source fabricated by combining a complementary metal oxide semiconductor (CMOS) micro-hotplate with a dielectric-encapsulated carbon nanotube (CNT) blackbody layer. The micro-hotplate was used during fabrication as a micro-reactor to facilitate high temperature (>700 [Formula: see text]C) growth of the CNT layer and also for post-growth thermal annealing. We demonstrate, for the first time, stable extended operation in air of devices with a dielectric-encapsulated CNT layer at heater temperatures above 600 [Formula: see text]C. The demonstrated devices exhibit almost unitary emissivity across the entire MIR spectrum, offering an ideal solution for low-cost, highly-integrated MIR spectroscopy for the Internet of Things.

Interfacial Engineering of Hybrid Polydopamine/Polypyrrole Nanosheets with Narrow Band Gaps for Fluorescence Sensing of MicroRNA.

Nanoquencher-based biosensors have emerged as powerful tools for the detection of tumor markers, where challenges in efficiently docking the π-electron interaction interface toward nucleic acid probes containing π-electron-rich units of bases and fluorescent dyes still remain. Herein, we present hybrid polydopamine/polypyrrole nanosheets (PDA-PPy-NS) with π electron coupling and ultranarrow band gap (0.29 eV) by interfacial engineering of polymer hybrids at the nanoscale. PDA-PPy-NS were first prepared through oxidant-induced polymerization of pyrrole on PDA nanosheets. By utilizing fluorescent-dye-labeled single-stranded DNA as a probe, the hybrid nanoquencher showed ultrahigh fluorescence quenching ability, i.e., a Cy5-ssDNA/nanoquencher mass ratio of 36.9 under the complete quenching condition, which is comparable to that of graphene oxide. It was demonstrated that the energy level coupling of nanosheets and nucleic acid dye (Cy5) was the key factor contributing to the efficient photoinduced electron transfer (PET). Subsequently, the nanoquencher/DNA probe was proved to possess superior sensitivity and selectivity for efficient and reliable detection of miRNA-21 with a detection limit of 23.1 pM. Our work proves that the π-electron-rich biosensor interface can significantly enhance the PET efficiency, providing a theoretical basis for developing novel high-performance sensors.

lncRNA C2dat2 facilitates autophagy and apoptosis via the miR-30d-5p/DDIT4/mTOR axis in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is an important pathophysiological process of ischemic stroke associated with various physiological and pathological processes, including autophagy and apoptosis. In this study, we examined the role and mechanism of long noncoding RNA CAMK2D-associated transcript 2 (C2dat2) in regulating CIRI in vivo and in vitro. C2dat2 up-regulation facilitated neuronal autophagy and apoptosis induced by CIRI. Mechanistically, C2dat2 acts as a competing endogenous RNA (ceRNA) to negatively regulate miR-30d-5p expression. More specifically, miR-30d-5p targeted the 3'-untranslated region of DNA damage-inducible transcript 4 (DDIT4) and silenced its target mRNA DDIT4. Additionally, C2dat2 binding with heat shock cognate 70/heat shock protein 90 blocked RNA-induced silencing complex assembly to abolish the miR-30d-5p targeting of DDIT4 and inhibited miR-30d-5p to silence its target mRNA DDIT4. Further analysis showed that C2dat2 knockdown conspicuously inhibited the up-regulation of DDIT4 and Beclin-1 levels and LC3B II/I ratio and the down-regulation of P62 and phosphorylated mammalian target of rapamycin (mTOR)/mTOR and phosphorylated-P70S6K/P70S6K ratio in Neuro-2a cells after oxygen-glucose deprivation/reoxygenation. This study first revealed that C2dat2/miR-30d-5p/DDIT4/mTOR forms a novel signaling pathway to facilitate autophagy and apoptosis induced by CIRI, contributing to the better understanding of the mechanisms of CIRI and enriching the ceRNA hypothesis in CIRI.

Intervention of Polydopamine Assembly and Adhesion on Nanoscale Interfaces: State-of-the-Art Designs and Biomedical Applications.

The translation of mussel-inspired wet adhesion to biomedical engineering fields have catalyzed the emergence of polydopamine (PDA)-based nanomaterials with privileged features and properties of conducting multiple interfacial interactions. Recent concerns and progress on the understanding of PDA's hierarchical structure and progressive assembly are inspiring approaches toward novel nanostructures with property and function advantages over simple nanoparticle architectures. Major breakthroughs in this field demonstrated the essential role of π-π stacking and π-cation interactions in the rational intervention of PDA self-assembly. In this review, the recently emerging concepts in the preparation and application of PDA nanomaterials, including 3D mesostructures, low-dimensional nanostructures, micelle/nanoemulsion based nanoclusters, as well as other multicomponent nanohybrids by the segregation and organization of PDA building blocks on nanoscale interfaces are outlined. The contribution of π-electron interactions on the interfacial loading/release of π electron-rich molecules (nucleic acids, drugs, photosensitizers) and the exogenous coupling of optical energy, as well as the impact of wet-adhesion interactions on the nano-bio interface interplay, are highlighted by discussing the structure-property relationships in their featured applications including fluorescent biosensing, gene therapy, drug delivery, phototherapy, combined therapy, etc. The limitations of current explorations, and future research directions are also discussed.