Leber's hereditary optic neuropathy (LHON) is a rare inherited blindness caused by mutations in the mitochondrial DNA (mtDNA). The disorder is untreatable and tricky, as the existing chemotherapeutic ...agent Idebenone alleviates symptoms rather than overcoming the underlying cause. Although some studies have made progress on allotopic expression for LHON, in situ mitochondrial gene therapy remains challenging, which may simplify delivery procedures to be a promising therapeutic for LHON. LHON becomes more difficult to manage in the changed mitochondrial microenvironment, including increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP). Herein, a pathologically responsive mitochondrial gene delivery vector named triphenylphosphine‐terminated poly(sulfur‐containing thioketal undecafluorohexylamine histamine) and Ide‐terminated poly(sulfur‐containing thioketal undecafluorohexylamine histamine) (TISUH) is reported to facilitate commendable in situ mitochondrial gene therapy for LHON. TISUH directly targets diseased mitochondria via triphenylphosphine and fluorination addressing the decreasing MMP. In addition, TISUH can be disassembled by high mitochondrial ROS levels to release functional genes for enhancing gene transfection efficiency and fundamentally correcting genetic abnormalities. In both traditional and gene‐mutation‐induced LHON mouse models, TISUH‐mediated gene therapy shows satisfactory curative effect through the sustained therapeutic protein expression in vivo. This work proposes a novel pathologically responsive in situ mitochondrial delivery platform and provides a promising approach for refractory LHON as well as other mtDNA mutated diseases treatments.
A pathologically responsive mitochondrial gene therapy referred to as “TISUH” in an allotopic expression‐independent manner achieves accurately in situ mitochondrial gene delivery. It is a novel nanomedicine harnessing pathological characteristics to import exogenous gene into mitochondria for Leber's hereditary optic neuropathy treatment, a capability that has potential to model mitochondrial DNA (mtDNA) mutated disorders and correct genetic abnormalities in other mtDNA mutated diseases.
Noncovalent forces are of considerable importance in the formation of self-assembled drug-delivery systems. In addition to non-destructively linking the delivery vehicle and guest drug, they provide ...multiple advantages, including protecting the structure of the drug, maintaining its functional effects, and facilitating its release. In particular, π-π stacking interactions have potential application in a comprehensive range of biomedical and biotechnological fields. Because they do not alter structural or functional properties of drugs, π-π stacking interactions have been used as a driving force in loading drugs into delivery systems, and in the design of self-assembling systems. Moreover, since the π-π stacking force is affected by environmental conditions such as pH, it has been used to design environment-responsive drug-delivery systems. In this review, we cover features of π-π stacking interactions and their applications to the design of drug-delivery systems. Carbon nanotubes, graphene-based nanomaterials, micelles and hydrogels-all delivery systems capable of π-π stacking interactions-are the focus. We also cover π-π stacking interaction-based loading of chemicals or biological drugs into delivery systems, and controlled release of drugs from delivery systems in certain environments. In addition, we examine the in vivo barriers for π-π stacking interaction-based drug delivery, and discuss challenges for clinical applications and future directions.
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•π-π stacking interactions have been used to deliver a variety of chemical drugs.•π-π interaction-based systems have been used in the delivery of biological drugs such as protein, cell, and nucleic acid.•Structural properties of materials affect the capability of π-π interactions.•Strategies have been used to protect π-π interaction-based drug-delivery systems in vivo.
Two standard Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) products, 3B42RT and 3B42V6, were quantitatively evaluated in the Laohahe basin, China, located ...within the TMPA product latitude band (50°NS) but beyond the inclined TRMM satellite latitude band (36°NS). In general, direct comparison of TMPA rainfall estimates to collocated rain gauges from 2000 to 2005 show that the spatial and temporal rainfall characteristics over the region are well captured by the 3B42V6 estimates. Except for a few months with underestimation, the 3B42RT estimates show unrealistic overestimation nearly year round, which needs to be resolved in future upgrades to the real‐time estimation algorithm. Both model‐parameter error analysis and hydrologic application suggest that the three‐layer Variable Infiltration Capacity (VIC‐3L) model cannot tolerate the nonphysical overestimation behavior of 3B42RT through the hydrologic integration processes, and as such the 3B42RT data have almost no hydrologic utility, even at the monthly scale. In contrast, the 3B42V6 data can produce much better hydrologic predictions with reduced error propagation from input to streamflow at both the daily and monthly scales. This study also found the error structures of both RT and V6 have a significant geo‐topography‐dependent distribution pattern, closely associated with latitude and elevation bands, suggesting current limitations with TRMM‐era algorithms at high latitudes and high elevations in general. Looking into the future Global Precipitation Measurement (GPM) era, the Geostationary Infrared (GEO‐IR) estimates still have a long‐term role in filling the inevitable gaps in microwave coverage, as well as in enabling sub‐hourly estimates at typical 4‐km grid scales. Thus, this study affirms the call for a real‐time systematic bias removal in future upgrades to the IR‐based RT algorithm using a simple scaling factor. This correction is based on MW‐based monthly rainfall climatologies applied to the combined monthly satellite‐gauge research products.
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•An ultrasound-assisted freeze-drying (UAFD) strategy is introduced.•UAFD enhances the freezing efficiency and regulates the porous structure.•Thermal insulation of polyimide (PI) ...aerogels prepared by UAFD is improved.•Hydrophobicity of PI aerogels prepared by UAFD is improved.•Electromagnetic interference property of aerogels prepared by UAFD is improved.
Owing to the unique structural characteristics, aerogel has broad utilization prospects in numerousapplication scenarios such as thermal insulation, electromagnetic interference shielding, adsorption, etc.As one of the most commonly used drying methods in aerogel preparation, freeze-drying avoids surface tension at the gas–liquid interface by constructing a gas–solid interface. However, problems such as relatively low freezing efficiency, aerogel structure destruction,excessive and uncontrollable pore size caused by uncontrolled growth of crystals during freezing processstill severely limit the preparation efficiency and performance of aerogel. In this work,the reported ultrasound-assisted freeze-drying (UAFD) strategy was applied to enhanced the freezing efficiency by cavitation-induced nucleation. Meanwhile, by affecting the secondary nucleation, UAFD strategy produced aerogel with smaller pore size and narrower pore size distribution. At the same time, the pore structure could be tuned by the regulation of ultrasonic power. The thermal insulation, hydrophobicity of polyimide (PI) aerogels and electromagnetic interference (EMI) shielding properties of PI-derived carbon aerogels prepared by UAFD strategy were significantly improved. The strategy proposed in this work provides a new path to achieve improvement of aerogel production efficiency and performance through structural regulation. Moreover, it could be extended to the preparation of other types of aerogels.
Highlights • Increased SCD1 expression is correlated with poor prognosis of HCC patients. • HCC patients with autophagy defect exhibit adverse clinic outcomes. • Inhibition of SCD1 impairs cell ...proliferation and induces apoptosis and autophagy in human HCC cells. • The human HCC cell death triggered by SCD1 inhibition is partly involved in autophagy-induced apoptosis via AMPK activation.
MoS2 nanosheets as a promising 2D nanomaterial have extensive applications in energy storage and conversion, but their electrochemical performance is still unsatisfactory as an anode for efficient ...Li+/Na+ storage. In this work, the design and synthesis of vertically grown MoS2 nanosheet arrays, decorated with graphite carbon and Fe2O3 nanoparticles, on flexible carbon fiber cloth (denoted as Fe2O3@C@MoS2/CFC) is reported. When evaluated as an anode for lithium‐ion batteries, the Fe2O3@C@MoS2/CFC electrode manifests an outstanding electrochemical performance with a high discharge capacity of 1541.2 mAh g−1 at 0.1 A g−1 and a good capacity retention of 80.1% at 1.0 A g−1 after 500 cycles. As for sodium‐ion batteries, it retains a high reversible capacity of 889.4 mAh g−1 at 0.5 A g−1 over 200 cycles. The superior electrochemical performance mainly results from the unique 3D ordered Fe2O3@C@MoS2 array‐type nanostructures and the synergistic effect between the C@MoS2 nanosheet arrays and Fe2O3 nanoparticles. The Fe2O3 nanoparticles act as spacers to steady the structure, and the graphite carbon could be incorporated into MoS2 nanosheets to improve the conductivity of the whole electrode and strengthen the integration of MoS2 nanosheets and CFC by the adhesive role, together ensuring high conductivity and mechanical stability.
The design of vertically grown MoS2 nanosheet arrays with expanded spacing of (002) plane, decorated with graphite carbon and Fe2O3 nanoparticles, on flexible carbon fiber cloth is reported. Due to the unique 3D ordered Fe2O3@C@MoS2 array‐type nanostructures, these electrodes manifest an outstanding electrochemical performance for lithium‐ion and sodium‐ion batteries.
Solid‐state batteries that employ solid‐state electrolytes (SSEs) to replace routine liquid electrolytes are considered to be one of the most promising solutions for achieving high‐safety lithium ...metal batteries. SSEs with high mechanical modulus, thermal stability, and non‐flammability can not only inhibit the growth of lithium dendrites but also enhance the safety of lithium metal batteries. However, several internal materials/electrodes‐related thermal hazards demonstrated by recent works show that solid‐state lithium metal batteries (SSLMBs) are not impenetrable. Therefore, understanding the potential thermal hazards of SSLMBs is critical for their more secure and widespread applications. In this contribution, we provide a comprehensive overview of the thermal failure mechanism of SSLMBs from materials to devices. Also, strategies to improve the thermal safety performance of SSLMBs are included from the view of material enhancement, battery design, and external management. Consequently, the future directions are further provided. We hope that this work can shed bright insights into the path of constructing energy storage devices with high energy density and safety.
Focusing on the safety hazards of SSLMBs, an in‐depth understanding of the thermal failure mechanisms of SSLMBs is classified and summarized from materials to devices. Beyond that, future directions in improving battery safety are also involved. This work sheds bright insights into the path of constructing energy storage devices with high energy density and safety.
Plant communities in nature are often challenged by multiple global change factors (GCFs) and also ubiquitously encountered with soil nutrient heterogeneity. So far, however, we know little about the ...interactive effect of multiple GCFs and soil nutrient heterogeneity on plant communities. We conducted an outdoor mesocosm experiment in which a plant community was either grown in heterogeneous soils consisting of high‐ and low‐nutrient patches, or in homogeneous soils where the same amount of nutrients was evenly distributed. These plant communities were exposed to none (control), single, or a combination of two or four GCFs (i.e. drought, nitrogen deposition, microplastic and cadmium). Biomass of the plant community exposed to drought and nitrogen deposition were greater in heterogeneous than in homogeneous soils, but evenness of the plant community exposed to microplastics was lower. Increasing the number of GCFs increased community biomass more in heterogeneous than in homogeneous soils, but it generally reduced community evenness, independent of soil nutrient heterogeneity. These contrasting responses were related to changing competitive hierarchies and root foraging responses under different treatments. Our results suggest that soil nutrient heterogeneity can alter community productivity and diversity via changing competitive interactions of the component species, depending on both the identity and the number of GCFs acting on the community. These results have important implications for the maintenance of ecosystem functions and services under rapid and complex ongoing global changes.
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