Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed.

IntroductionIn guiding human embryonic stem cell (hESC) technology toward the clinic, 1 key issue to be addressed is a lack of standardization in the culture and maintenance of hESCs. In the absence of mouse embryonic fibroblast (MEF) feeder layers, many researchers rely on "conditioning" in which medium is first exposed to MEFs to acquire soluble factors that support the propagation of undifferentiated hESCs in culture. It has been difficult to discern how MEF conditioning enables hESCs to maintain an undifferentiated state. Other common features of more recently developed hESC culture conditions include the presence of fibroblast growth factor-2 (FGF2), the absence of serum, and the presence of a serum substitute such as KnockOut Serum Replacer (KSR, proprietary formulation; Invitrogen, Carlsbad, CA). [1][2][3] Other factors suggested to play a role in supporting the maintenance of hESCs include transforming growth factor ␤1 (TGF␤1), 4 activin A (ActA), 5,6 platelet-derived growth factor (PDGF) and sphingosine-1-phosphate, 7 BIO, a small-molecule inhibitor of GSK3␤, 8 and neurotrophins. 9 Several defined medium systems have been described for hESCs and are based upon FGF2 in combination with nodal, 10 TGF␤1, GABA, and pipecolic acid, plus lithium chloride, 11 Wnt3a plus April/BAFF, 12 or the N2/B27 supplements. 13 Although these studies have focused on identifying growth factors and conditions that support the proliferation of undifferentiated hESCs, little is known about the cell-surface receptors that are activated when hESCs are exposed to conditions favorable for self-renewal. A number of receptor tyrosine kinases (RTKs) are expressed at high levels on hESCs, 14 including insulin-like growth factor-1 receptor (IGF1R), fibroblast growth factor receptor (FGFR1), and EPHA1, as well as ERBB2 and ERBB3 (which are members of the epidermal growth factor receptor [EGFR] family), while expression of FGFR2 (EGFR) FGFR4, vascular endothelial growth factor receptor-2 (VEGFR2), IGFR2, KIT, and RET has also been detected. 15,16 RTKs are likely to be central signaling effectors 17 that influence survival, apoptosis, proliferation, or differentiation decisions in pluripotent cells. To determine if any of these RTKs are involved in self-renewal, we simultaneously interrogated the tyrosine phosphorylation status of 42 RTKs in hESCs grown in MEF-conditioned medium (CM) and developed a defined medium for hESC culture. The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. For personal use only. on May 7, 2018. by guest www.bloodjournal.org From Materials and methods Cell cultureThe National Institutes of Health (NIH)-registered H1, BG01, BG02, and BG03 hESC lines, as well as CyT49, an hESC line isolated using human feeder cells under good manufacturing process (GMP) conditions (Novocell, San Diego, CA), we...

Atomically dispersed metal catalysts for the oxygen reduction reaction, including their synthesis, characterization, reaction mechanisms and electrochemical energy application, are reviewed.

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane vesicles derived from most cell types. Carrying diverse biomolecules from their parent cells, EVs are important mediators of intercellular communication and thus play significant roles in physiological and pathological processes. Owing to their natural biogenesis process, EVs are generated with high biocompatibility, enhanced stability, and limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic delivery vehicles. EVs have been reported to be used for the delivery of siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, and CRISPR/Cas9 in the treatment of various diseases. As a natural drug delivery vectors, EVs can penetrate into the tissues and be bioengineered to enhance the targetability. Although EVs' characteristics make them ideal for drug delivery, EV-based drug delivery remains challenging, due to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS. ARTICLE HISTORY

Relation classification is a crucial ingredient in numerous information extraction systems seeking to mine structured facts from text. We propose a novel convolutional neural network architecture for this task, relying on two levels of attention in order to better discern patterns in heterogeneous contexts. This architecture enables endto-end learning from task-specific labeled data, forgoing the need for external knowledge such as explicit dependency structures. Experiments show that our model outperforms previous state-of-the-art methods, including those relying on much richer forms of prior knowledge.

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Heat waves (HWs) are projected to become more frequent and last longer over most land areas in the late 21st century, which raises serious public health concerns. Urban residents face higher health risks due to synergies between HWs and urban heat islands (UHIs) (i.e., UHIs are higher under HW conditions). However, the responses of urban and rural surface energy budgets to HWs are still largely unknown. This study analyzes observations from two flux towers in Beijing, China and reveals significant differences between the responses of urban and rural (cropland) ecosystems to HWs. It is found that UHIs increase significantly during HWs, especially during the nighttime, implying synergies between HWs and UHIs. Results indicate that the urban site receives more incoming shortwave radiation and longwave radiation due to HWs as compared to the rural site, resulting in a larger radiative energy input into the urban surface energy budget. Changes in turbulent heat fluxes also diverge strongly for the urban site and the rural site: latent heat fluxes increase more significantly at the rural site due to abundant available water, while sensible heat fluxes and possibly heat storage increase more at the urban site. These comparisons suggest that the contrasting responses of urban and rural surface energy budgets to HWs are responsible for the synergies between HWs and UHIs. As a result, urban mitigation and adaption strategies such as the use of green roofs and white roofs are needed in order to mitigate the impact of these synergies.

SUMMARY Recent evidence indicates that mouse and human embryonic stem (ES) cells are fixed at different developmental stages, with the former positioned earlier. We show that a narrow concentration of the naturally occurring short chain fatty acid, sodium butyrate, supports the extensive self-renewal of mouse and human ES cells, while promoting their convergence toward an intermediate stem cell state. In response to butyrate human ES cells regress to an earlier developmental stage characterized by a gene expression profile resembling that of mouse ES cells, preventing precocious Xist expression, while retaining the ability to form complex teratomas in vivo. Other histone deacetylase inhibitors (HDACi) also support human ES cell self-renewal. Our results indicate that HDACi can promote ES cell self-renewal across species, and demonstrate that ES cells can toggle between alternative states in response to environmental factors.