The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of Streptococcus suis , a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of S. suis emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of S. suis and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of S. suis is yet to be fully realized.

Development of inhibitors for ubiquitin pathway has been suggested as a promising strategy to treat several types of cancers, which has been showcased by recent success of a series of novel anticancer drugs based on inhibition of ubiquitin pathways. Although the druggability of enzymes in ubiquitin pathways has been demonstrated, ubiquitin itself, the main agent of the pathway, has not been targeted. Whereas conventional enzyme inhibitors are used to silence the ubiquitination or reverse it, they cannot disrupt the binding activity of ubiquitin. Herein, we report that the scaffolds of sulfonated aryl diazo compounds, particularly Congo red, could disrupt the binding activity of ubiquitin, resulting in the activity equivalent to inhibition of ubiquitination. NMR mapping assay demonstrated that the chemical directly binds to the recognition site for ubiquitin processing enzymes on the surface of ubiquitin, and thereby blocks the binding of ubiquitin to its cognate receptors. As a proof of concept for the druggability of the ubiquitin molecule, we demonstrated that Congo red acted as an intracellular inhibitor of ubiquitin recognition and binding, which led to inhibition of ubiquitination, and thereby, could be used as a sensitizer for conventional anticancer drugs, doxorubicin.

In Myanmar, where backyard, semi-intensive, and intensive pig (Sus scrofa domesticus) farming coexist, there is limited understanding of the zoonotic risks and antimicrobial resistance (AMR) associated with these farming practices. This study was conducted to investigate the prevalence, AMR and genomic features of Salmonella in pig farms in the Yangon region and the impact of farm intensification to provide evidence to support risk-based future management approaches. Twenty-three farms with different production scales were sampled for two periods with three sampling-visit each. Antimicrobial susceptibility tests and whole-genome sequencing were performed on the isolates. The prevalence of Salmonella was 44.5% in samples collected from backyard farms, followed by intensive (39.5%) and semi-intensive farms (19.5%). The prevalence of multi-drug resistant isolates from intensive farms (45/84, 53.6%) was higher than those from backyard (32/171, 18.7%) and semi-intensive farms (25/161, 15.5%). Among 28 different serovars identified, S. Weltevreden (40; 14.5%), S. Kentucky (38; 13.8%), S. Stanley (35, 12.7%), S. Typhimurium (22; 8.0%) and S. Brancaster (20; 7.3%) were the most prevalent serovars and accounted for 56.3% of the genome sequenced strains. The diversity of Salmonella serovars was highest in semi-intensive and backyard farms (21 and 19 different serovars, respectively). The high prevalence of globally emerging S. Kentucky ST198 was detected on backyard farms. The invasive-infection linked typhoid-toxin gene (cdtB) was found in the backyard farm isolated S. Typhimurium, relatively enriched in virulence and AMR genes, presented an important target for future surveillance. While intensification, in terms of semi-intensive versus backyard production, maybe a mitigator for zoonotic risk through a lower prevalence of Salmonella, intensive production appears to enhance AMR-associated risks. Therefore, it remains crucial to closely monitor the AMR and virulence potential of this pathogen at all scales of production. The results underscored the complex relationship between intensification of animal production and the prevalence, diversity and AMR of Salmonella from pig farms in Myanmar.

Đặt vấn đề: Trên thực tế, phần lớn các trường hợp ung thư biểu mô tế bào gan (UTBMTBG) sẽ tiến triển hoặc không dung nạp với điều trị toàn thân bước một. Ngoài ra, điều trị tiêu chuẩn UTBMTBG bước hai cũng như trình tự của các bước sau đó vẫn chưa được thống nhất. Đề tài xác định thời gian sống còn không bệnh tiến triển (PFS), tỉ lệ đáp ứng (ORR), thời gian sống còn toàn bộ (OS), độc tính điều trị sau thất bại bước một UTBMTBG. Đối tượng, phương pháp: Nghiên cứu mô tả hồi cứu cắt ngang trên 12 BN UTBMTBG tiến triển sau điều trị bước 1 tại Bệnh viện Ung Bướu TP. HCM. Kết quả: Tỉ lệ đáp ứng điều trị bước 2 là 8.3%, tỉ lệ kiểm soát bệnh là 33.3%. Trung vị thời gian sống còn không bệnh tiến triển với điều trị bước 2 (mPFS2) là 3.0 tháng và với điều trị bước 3 (mPFS3) là 2.1 tháng. Trung vị thời gian sống còn không bệnh sau thất bại điều trị bước 1 là 7.1 tháng. Có 80% các trường hợp ghi nhận độc tính xảy ra khi tiếp tục điều trị toàn thân. Tuy nhiên, các độc tính chủ yếu độ 1 - 2 và thường xảy ra ở bước điều trị sau đó. Kết luận: Lựa chọn điều trị toàn thân trên nhóm bệnh nhân UTBMTBG tiến triển sau điều trị bước một cần được đánh giá đầy đủ về điều trị bước một trước đó, đặc điểm lâm sàng bệnh nhân cũng như dự đoán khả năng độc tính có thể xảy ra để có thể đưa ra quyết định điều trị nhằm đem lại hiệu quả tốt nhất cho người bệnh.