The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-γ production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis.

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Bone-implant-associated infections are common after orthopedic surgery due to impaired host immune response around the implants. In particular, when a biofilm develops, the immune system and antibiotic treatment find it difficult to eradicate, which sometimes requires a second operation to replace the infected implants. Most strategies have been designed to prevent biofilms from forming on the surface of bone implants, but these strategies cannot eliminate the biofilm when it has been established in vivo. To address this issue, a nonsurgical, noninvasive treatment for biofilm infection must be developed. Herein, a red-phosphorus-IR780-arginine-glycine-aspartic-acid-cysteine coating on titanium bone implants is prepared. The red phosphorus has great biocompatibility and exhibits efficient photothermal ability. The temperature sensitivity of Staphylococcus aureus biofilm is enhanced in the presence of singlet oxygen ( O ) produced by IR780. Without damaging the normal tissue, the biofilm can be eradicated through a safe near-infrared (808 nm) photothermal therapy at 50 °C in vitro and in vivo. This approach reaches an antibacterial efficiency of 96.2% in vivo with 10 min of irradiation at 50 °C. Meanwhile, arginine-glycine-aspartic-acid-cysteine decorated on the surface of the implant can improve the cell adhesion, proliferation, and osteogenic differentiation.

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The expression of the genomic information of severe acute respiratory syndrome coronavirus (SARS CoV) involves synthesis of a nested set of subgenomic RNAs (sgRNAs) by discontinuous transcription. In SARS CoV-infected cells, 10 sgRNAs, including 2 novel ones, were identified, which were predicted to be functional in the expression of 12 open reading frames located in the 3 one-third of the genome. Surprisingly, one new sgRNA could lead to production of a truncated spike protein. Sequence analysis of the leader-body fusion sites of each sgRNA showed that the junction sequences and the corresponding transcription-regulatory sequence (TRS) are unique for each species of sgRNA and are consistent after virus passages. For the two novel sgRNAs, each used a variant of the TRS that has one nucleotide mismatch in the conserved hexanucleotide core (ACGAAC) in the TRS. Coexistence of both plus and minus strands of SARS CoV sgRNAs and evidence for derivation of the sgRNA core sequence from the body core sequence favor the model of discontinuous transcription during minus-strand synthesis. Moreover, one rare species of sgRNA has the junction sequence AAA, indicating that its transcription could result from a noncanonical transcription signal. Taken together, these results provide more insight into the molecular mechanisms of genome expression and subgenomic transcription of SARS CoV.Severe acute respiratory syndrome (SARS) is an atypical form of pneumonia that was first recognized in Guangdong Province, China, in November 2002, and its causative agent was identified as novel a coronavirus (SARS CoV) (7,9,14). Coronaviruses are the largest RNA viruses, containing a single-stranded, plus-sense RNA ranging from 27 to 31.5 kb in size. The genomes of coronaviruses, possessing a 5Ј cap structure and 3Ј poly(A) tail, are polycistronic and are expressed through a poorly understood regulatory mechanism (11). The two large open reading frames (ORFs) (1a and 1b) at the 5Ј end of the genome encode the viral replicase and are translated directly from the genomic RNA, while ORF 1b is expressed by Ϫ1 ribosomal frameshifting (26). The 3Ј one-third of the genome comprises the genes encoding the structural and auxiliary proteins translated through six to nine nested and 3Ј-coterminal subgenomic RNAs (sgRNAs), but the number, composition, and expression strategies of the 3Ј-proximal ORFs vary greatly among coronaviruses, although four genes for the structural proteins S, E, M, and N are always included (11).A unique feature for coronaviruses and some related viruses in the order Nidovirales is that the viral sgRNAs contain a common leader sequence of 55 to 92 nucleotides (nt), which is derived from the 5Ј end of the genomic RNA (11). It has been shown that the synthesis of each subgenomic mRNA involves a discontinuous step by which the so-called 3Ј body sequence is fused to the genomic 5Ј leader sequence (22). The fusion of leader and body sequences during discontinuous transcription is determined, at least in part, by cis-acting elements term...

Despite the development of advanced antibacterial materials, bacterial infection is still a serious problem for wound healing because it usually induces severe complications and cannot be eradicated completely. Most current materials cannot simultaneously provide antibacterial activity, reusability, and biocompatibility as well as participate in stimulating cell behaviors to promote bacteria-accompanied wound healing. This work fabricated a hybrid hydrogel embedded with two-dimensional (2D) few-layer black phosphorus nanosheets (BPs) via simple electrostatic interaction. Within 10 min, 98.90% Escherichia coli and 99.51% Staphylococcus aureus can be killed rapidly by this hybrid, due to its powerful ability to produce singlet oxygen (O) under simulated visible light. In addition, this hydrogel also shows a high repeatability; that is, the antibacterial efficacy can still reach up to 95.6 and 94.58% against E. coli and S. aureus, respectively, even after challenging bacteria up to four times repeatedly. In vitro and in vivo results reveal that BPs in this hybrid hydrogel can promote the formation of the fibrinogen at the early stages during the tissue reconstruction process for accelerated incrustation. In addition, BPs can also trigger phosphoinositide 3-kinase (PI3K), phosphorylation of protein kinase B (Akt), and extracellular signal-regulated kinase (ERK1/2) signaling pathways for enhanced cellular proliferation and differentiation. Moreover, the hydrogel causes no appreciable abnormalities or damage to major organs (heart, liver, spleen, lung, and kidney) in rats during the wound healing process. Therefore, this BP-based hydrogel will have great potential as a safe multimodal therapeutic system for active wound healing and sterilization.

Recently, Convolutional Neural Networks (ConvNets) have shown promising performances in many computer vision tasks, especially imagebased recognition. How to effectively use ConvNets for video-based recognition is still an open problem. In this paper, we propose a compact, effective yet simple method to encode spatiotemporal information carried in 3D skeleton sequences into multiple 2D images, referred to as Joint Trajectory Maps (JTM), and ConvNets are adopted to exploit the discriminative features for real-time human action recognition. The proposed method has been evaluated on three public benchmarks, i.e., MSRC-12 Kinect gesture dataset (MSRC-12), G3D dataset and UTD multimodal human action dataset (UTD-MHAD) and achieved the state-of-the-art results.

The study confirms the intrinsic and extrinsic motivators on work engagement posited by job demands-resources model. Theory-driven strategies to improve work environment, enhance job characteristics and promote wok engagement are needed to address the nursing shortage and high turnover intention among experienced nurses.