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The synergistic effect of chemotherapy and ablation using high-intensity focused ultrasound (HIFU) is realized with a newly developed drug-delivery system. The system comprises an ultrathin silica shell surrounding a poly(lactic-co-glycolic acid) nanoemulsion core containing the drug (CPT) and a perfluorocarbon (PFOB). This nanosystem presents many advantages in drug delivery, such as excellent structural stability, high drug-loading capacity, and rapid HIFU-mediated drug release.

Microbes play an essential role in the decomposition process but were poorly understood in their succession and behaviour. Previous researches have shown that microbes show predictable behaviour that starts at death and changes during the decomposition process. Research of such behaviour enhances the understanding of decomposition and benefits estimating the postmortem interval (PMI) in forensic investigations, which is critical but faces multiple challenges. In this study, we combined microbial community characterization, microbiome sequencing from different organs (i.e. brain, heart and cecum) and machine learning algorithms [random forest (RF), support vector machine (SVM) and artificial neural network (ANN)] to investigate microbial succession pattern during corpse decomposition and estimate PMI in a mouse corpse system. Microbial communities exhibited significant differences between the death point and advanced decay stages. Enterococcus faecalis, Anaerosalibacter bizertensis, Lactobacillus reuteri, and so forth were identified as the most informative species in the decomposition process. Furthermore, the ANN model combined with the postmortem microbial data set from the cecum, which was the best combination among all candidates, yielded a mean absolute error of 1.5 AE 0.8 h within 24-h decomposition and 14.5 AE 4.4 h within 15-day decomposition. This integrated model can serve as a reliable and accurate technology in PMI estimation.

The MYB proteins represent a large family of transcription factors and play important roles in development, senescence, and stress responses in plants. In the current study, 233 MYB transcription factor-encoding genes were identified and analyzed in the potato genome, including 119 R1-MYB, 112 R2R3-MYB, and two R1R2R3-MYB members. R2R3-MYB is the most abundant MYB subclass and potato R2R3-MYB members together with their Arabidopsis homologs were divided into 35 well-supported subgroups as the result of phylogenetic analyses. Analyses on gene structure and protein motif revealed that members from the same subgroup shared similar exon/intron and motif organization, further supporting the results of phylogenetic analyses. Evolution of the potato MYB family was studied via syntenic analysis. Forty-one pairs of StMYB genes were predicted to have arisen from tandem or segmental duplication events, which played important roles in the expansion of the StMYB family. Expression profiling revealed that the StMYB genes were expressed in various tissues and several StMYB genes were identified to be induced by different stress conditions. Notably, StMYB030 was found to act as the homolog of AtMYB44 and was significantly up-regulated by salt and drought stress treatments. Furthermore, overexpression of StMYB030 in Arabidopsis enhanced salt stress tolerance of transgenic plants. The results from this study provided information for further functional analysis and for crop improvements through genetic manipulation of these StMYB genes.

SummaryWe have previously described two types of protective B-cell epitopes in the O-antigen (OAg) of the Gram-negative bacterium Francisella tularensis: repeating internal epitopes targeted by the vast majority of anti-OAg monoclonal antibodies (mAbs), and a non-overlapping epitope at the non-reducing end targeted by the previously unique IgG2a mAb FB11. We have now generated and characterized three mAbs specific for the non-reducing end of F. tularensis OAg, partially encoded by the same variable region germline genes, indicating that they target the same epitope. Like FB11, the new mAbs, Ab63 (IgG3), N213 (IgG3) and N62 (IgG2b), had higher antigen-binding bivalent avidity than internally binding antiOAg mAbs, and an oligosaccharide containing a single OAg repeat was sufficient for optimal inhibition of their antigen-binding. The X-ray crystal structure of N62 Fab showed that the antigen-binding site is lined mainly by aromatic amino acids that form a small cavity, which can accommodate no more than one and a third sugar residues, indicating that N62 binds mainly to the terminal Qui4NFm residue at the nonreducing end of OAg. In efficacy studies with mice infected intranasally with the highly virulent F. tularensis strain SchuS4, N62, N213 and Ab63 prolonged survival and reduced blood bacterial burden. These results yield insights into how antibodies to non-reducing ends of microbial polysaccharides can contribute to immune protection despite the smaller size of their target epitopes compared with antibodies to internal polysaccharide regions.

Objective We previously identified HLA–DR‐presented epitopes from a 27‐kd protein of Prevotella copri (Pc) obtained from peripheral blood mononuclear cells (PBMCs) from 1 rheumatoid arthritis (RA) patient. Herein, we sought to identify other HLA–DR‐presented Pc peptides and source proteins in PBMCs from additional patients to better understand Pc immune responses and RA disease pathogenesis. Methods Using tandem mass spectrometry, we searched for HLA–DR‐presented Pc peptides in PBMCs from RA and Lyme arthritis (LA) patients. The identified peptides and source proteins were tested for reactivity in RA patients, those with other arthritides, and the general population. These results were assessed for correlation with clinical findings. Results Including Pc‐p27, we identified 5 HLA–DR‐presented Pc peptides, each derived from a different Pc protein, in 3 of 4 RA patients, but none in 2 LA patients. When tested in our RA cohort, 14 of 19 patients (74%) had T cell responses, and 47 of 89 patients (53%) had IgG or IgA responses to ≥1 of the 5 Pc peptides or proteins, most commonly IgA reactivity with Pc‐p27. Additionally, 74% of RA patients with IgA antibodies to ≥1 Pc protein had anti–citrullinated protein antibodies (ACPAs) compared with 49% of patients who lacked IgA Pc antibody responses (P = 0.05), and IgA Pc antibody levels correlated with ACPA values. Conclusion The majority of the RA patients had Pc immune responses. The correlation of IgA Pc antibody responses, particularly to Pc‐p27, with ACPA supports the hypothesis that specific microbial antigens in the mucosa have a role in shaping or amplifying immune responses in RA joints.

Testis development is a vital and tightly regulated process in mammals. Understanding the biological mechanisms underlying testis development will benefit the animal reproduction industry. Expression changes in microRNA and messenger RNA in response to dynamic regulation effects have been associated with this process. However, very little is known about the roles of these molecules in yak development. Using whole-genome small RNA and messenger RNA sequencing, we performed a comprehensive analysis of the microRNA–messenger RNA interaction network expression in the testicles of Tianzhu white yaks during three developmental stages. Using Short Time-series Expression Miner analysis we identified 589 differentially expressed microRNAs (DERs) and 3383 differentially expressed messenger RNAs (DEGs) in the three age groups. A total of 93 unique DEGs are primarily involved in reproduction and testis development. Subsequently, four integration networks were constructed according to the DEGs and DERs in three biological processes. Nineteen DEGs were potentially regulated by 60 DERs, of which miR-574 and target gene AURKA played a crucial role in yak testis development and reproduction. The results of this study provide a basis for further exploration of the microRNA–messenger RNA interactions in testis development and reproduction and aid in uncovering the molecular mechanisms of spermatogenesis in male mammals.

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