In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.

Language model pre-training, such as BERT, has significantly improved the performances of many natural language processing tasks. However, pre-trained language models are usually computationally expensive, so it is difficult to efficiently execute them on resourcerestricted devices. To accelerate inference and reduce model size while maintaining accuracy, we first propose a novel Transformer distillation method that is specially designed for knowledge distillation (KD) of the Transformer-based models. By leveraging this new KD method, the plenty of knowledge encoded in a large "teacher" BERT can be effectively transferred to a small "student" Tiny-BERT. Then, we introduce a new two-stage learning framework for TinyBERT, which performs Transformer distillation at both the pretraining and task-specific learning stages. This framework ensures that TinyBERT can capture the general-domain as well as the task-specific knowledge in BERT. TinyBERT 41 with 4 layers is empirically effective and achieves more than 96.8% the performance of its teacher BERT BASE on GLUE benchmark, while being 7.5x smaller and 9.4x faster on inference. TinyBERT 4 is also significantly better than 4-layer state-of-the-art baselines on BERT distillation, with only ∼28% parameters and ∼31% inference time of them. Moreover, TinyBERT 6 with 6 layers performs on-par with its teacher BERT BASE .

Microbial activities shape the biogeochemistry of the planet and macroorganism health. Determining the metabolic processes performed by microbes is important both for understanding and for manipulating ecosystems (for example, disruption of key processes that lead to disease, conservation of environmental services, and so on). Describing microbial function is hampered by the inability to culture most microbes and by high levels of genomic plasticity. Metagenomic approaches analyse microbial communities to determine the metabolic processes that are important for growth and survival in any given environment. Here we conduct a metagenomic comparison of almost 15 million sequences from 45 distinct microbiomes and, for the first time, 42 distinct viromes and show that there are strongly discriminatory metabolic profiles across environments. Most of the functional diversity was maintained in all of the communities, but the relative occurrence of metabolisms varied, and the differences between metagenomes predicted the biogeochemical conditions of each environment. The magnitude of the microbial metabolic capabilities encoded by the viromes was extensive, suggesting that they serve as a repository for storing and sharing genes among their microbial hosts and influence global evolutionary and metabolic processes.

In our previous study we reported that the interaction of nanoparticles with cells can be influenced by particle shape, but until now the effect of particle shape on in vivo behavior remained poorly understood. In the present study, we control the fabrication of fluorescent mesoporous silica nanoparticles (MSNs) by varying the concentration of reaction reagents especially to design a series of shapes. Two different shaped fluorescent MSNs (aspect ratios, 1.5, 5) were specially designed, and the effects of particle shape on biodistribution, clearance and biocompatibility in vivo were investigated. Organ distributions show that intravenously administrated MSNs are mainly present in the liver, spleen and lung (>80%) and there is obvious particle shape effects on in vivo behaviors. Short-rod MSNs are easily trapped in the liver, while long-rod MSNs distribute in the spleen. MSNs with both aspect ratios have a higher content in the lung after PEG modification. We also found MSNs are mainly excreted by urine and feces, and the clearance rate of MSNs is primarily dependent on the particle shape, where short-rod MSNs have a more rapid clearance rate than long-rod MSNs in both excretion routes. Hematology, serum biochemistry, and histopathology results indicate that MSNs would not cause significant toxicity in vivo, but there is potential induction of biliary excretion and glomerular filtration dysfunction. These findings may provide useful information for the design of nanoscale delivery systems and the environmental fate of nanoparticles.

Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minimal invasiveness and high specificity. In this study, we demonstrate self-assembled copper−amino acid mercaptide nanoparticles (Cu-Cys NPs) for in situ glutathione-activated and H 2 O 2 -reinforced chemodynamic therapy for drugresistant breast cancer. After endocytosis into tumor cells, the Cu-Cys NPs could first react with local GSH, induce GSH depletion, and reduce Cu 2+ to Cu + . Subsequently, the generated Cu + would react with local H 2 O 2 to generate toxic hydroxyl radicals (•OH) via a Fenton-like reaction, which has a fast reaction rate in the weakly acidic TME, that are responsible for tumor-cell apoptosis. Due to the high GSH and H 2 O 2 concentration in tumor cells, which sequentially triggers the redox reactions, Cu-Cys NPs exhibited relatively high cytotoxicity to cancer cells, whereas normal cells were left alive. The in vivo results also proved that Cu-Cys NPs efficiently inhibited drug-resistant breast cancer without causing obvious systemic toxicity. As a novel copper mercaptide nanoformulation responsive to the TME, these Cu-Cys NPs may have great potential in chemodynamic cancer therapy.

A new species of parvovirus tentatively named human bocavirus 4 (HBoV4) was genetically characterized. Among 641 feces samples from children and adults the most commonly detected bocaviruses species were HBoV2>HBoV3>HBoV4>HBoV1 with HBoV2 prevalence of 21% and 26% in Nigerian and Tunisian children. HBoV3 and HBoV4 species combined were found in 12/192 cases of non-polio acute flaccid paralysis (AFP) from Tunisia and Nigeria and 0/96 healthy Tunisian contacts (p=0.01). Evidence of extensive recombination at the NP1 and VP1 gene boundary between and within species was found. The multiple species and high degree of genetic diversity seen among the human bocaviruses found in feces relative to the highly homogeneous HBoV1 suggest that this world-wide distributed respiratory pathogen may have recently evolved from an enteric bocavirus, perhaps after acquiring an expanded tropism favoring the respiratory track. Elucidating the possible role of the newly identified enteric bocaviruses in human diseases including AFP and diarrhea will require further epidemiological studies.

Recently, plasmonic copper sulfide (Cu2-xS) nanocrystals (NCs) have attracted much attention as materials for photothermal therapy (PTT). Previous reports have correlated photoinduced cell death to the photothermal heat mechanism of these NCs, and no evidence of their photodynamic properties has been reported yet. Herein we have prepared physiologically stable near-infrared (NIR) plasmonic copper sulfide NCs and analyzed their photothermal and photodynamic properties, including therapeutic potential in cultured melanoma cells and a murine melanoma model. Interestingly, we observe that, besides a high PTT efficacy, these copper sulfide NCs additionally possess intrinsic NIR induced photodynamic activity, whereupon they generate high levels of reactive oxygen species. Furthermore, in vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited. This study highlights a mechanism of NIR light induced cancer therapy, which could pave the way toward more effective nanotherapeutics.

materials, [2] and their coupled composites. [3] Among them, TM singleatom catalysts (SACs) have recently emerged as a new type of frontier materials with high activity, stability, and selectivity, rendering the great potential for diverse catalytic systems. [4] The unique electronic structure, maximized atomutilization efficiency, and unsaturated coordination bonds of the active centers in SACs contribute to the enhanced performance. [5] Moreover, recent investigations have demonstrated that the introduction of secondary metal atoms can further enhance the activity of SACs, indicating the promising development of dual-metal SACs. [6] Nevertheless, on the one hand, there is a serious lack of effective strategies to achieve the atomic control of targeted reactive sites comprising binary metal atoms; on the other hand, the identification of the diatomic structure in dual-metal SACs and the deeper functional mechanism of bimetallic atoms for synergistic catalysis are still in their infancy.Owing to the increasing concerns from energy and environmental issues, growing attention has been paid on developing sustainable energy conversion and storage technologies, such as water-splitting electrolyzers, fuel cells, metal-air batteries, etc. [7] However, the sluggish kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) on the electrodes has been proven to With the inspiration of developing bifunctional electrode materials for reversible oxygen electrocatalysis, one strategy of heteroatom doping is proposed to fabricate dual metal single-atom catalysts. However, the identification and mechanism functions of polynary single-atom structures remain elusive. Atomically dispersed binary Co-Ni sites embedded in N-doped hollow carbon nanocubes (denoted as CoNi-SAs/NC) are synthesized via proposed pyrolysis of dopamine-coated metalorganic frameworks. The atomically isolated bimetallic configuration in CoNi-SAs/NC is identified by combining microscopic and spectroscopic techniques. When employing as oxygen electrocatalysts in alkaline medium, the resultant CoNi-SAs/NC hybrid manifests outstanding catalytic performance for bifunctional oxygen reduction/evolution reactions, boosting the realistic rechargeable zinc-air batteries with high efficiency, low overpotential, and robust reversibility, superior to other counterparts and state-of-the-art precious-metal catalysts. Theoretical computations based on density functional theory demonstrate that the homogenously dispersed single atoms and the synergistic effect of neighboring Co-Ni dual metal center can optimize the adsorption/desorption features and decrease the overall reaction barriers, eventually promoting the reversible oxygen electrocatalysis. This work not only sheds light on the controlled synthesis of atomically isolated advanced materials, but also provides deeper understanding on the structure-performance relationships of nanocatalysts with multiple active sites for various catalytic applications.To date, large numbers of low cost and efficie...