Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, Including in Human and Poultry

Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and is of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increased rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarizes the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage–antibiotic combination therapy, phage-derived enzymes active on Acinetobacter baumannii and some novel technologies based on phage interventions. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions, especially in regard to its in vivo applications, before possible routine clinical use

Critical Roles of STAT3 in β-Adrenergic Functions in the Heart

BACKGROUND: β-Adrenergic receptors (βARs) play paradoxical roles in the heart. On one hand, βARs augment cardiac performance to fulfill the physiological demands, but on the other hand, prolonged activations of βARs exert deleterious effects that result in heart failure. The signal transducer and activator of transcription 3 (STAT3) plays a dynamic role in integrating multiple cytokine signaling pathways in a number of tissues. Altered activation of STAT3 has been observed in failing hearts in both human patients and animal models. Our objective is to determine the potential regulatory roles of STAT3 in cardiac βAR-mediated signaling and function. METHODS AND RESULTS: We observed that STAT3 can be directly activated in cardiomyocytes by β-adrenergic agonists. To follow up this finding, we analyzed βAR function in cardiomyocyte-restricted STAT3 knockouts and discovered that the conditional loss of STAT3 in cardiomyocytes markedly reduced the cardiac contractile response to acute βAR stimulation, and caused disengagement of calcium coupling and muscle contraction. Under chronic β-adrenergic stimulation, Stat3cKO hearts exhibited pronounced cardiomyocyte hypertrophy, cell death, and subsequent cardiac fibrosis. Biochemical and genetic data supported that Gαs and Src kinases are required for βAR-mediated activation of STAT3. Finally, we demonstrated that STAT3 transcriptionally regulates several key components of βAR pathway, including β1AR, protein kinase A, and T-type Ca(2+) channels. CONCLUSIONS: Our data demonstrate for the first time that STAT3 has a fundamental role in βAR signaling and functions in the heart. STAT3 serves as a critical transcriptional regulator for βAR-mediated cardiac stress adaption, pathological remodeling, and heart failure

戦後日本における華僑組織に関する考察―神戸中華青年会の設立と初期活動を中心に―

本稿では終戦直後に設立された神戸中華青年会が神戸華僑の社会的地位の向上のために行った諸活動について検討を試みた。神戸広東華僑を中心に設立された神戸中華青年会は、神戸華僑の社会的地位の改善のため、華僑自らが「戦勝国国民」としての自己意識を持ち、さまざまな文化活動を展開することによって、華僑内部の文化的素養を高め、同時に、日本社会に華僑の新たな存在感を見せつけることができた。これらの活動は、終戦直後の神戸華僑、延いては日本全域の華僑の社会的地位の向上に重要な役割を果たした。This paper analyzes the activities carried out by the Kobe Chinese Youth Association for enhancing the social status of Chinese resedents in Kobe in the post-war period of chaos. During this period, young Chinese in Kobe, most of whom were Cantonese, voluntarily set up the Youth Association for the purpose of facilitating their acceptance as "nationals from a victorious nation" and carried out various cultural and educational activities for self-improvement. They played an important role in enhancing the social status of overseas Chainese in Kobe and even in the whole of Japan

戦後朝鮮華僑の職業に関する考察(1945-1958)

第二次世界大戦後、北朝鮮では社会主義建設に向けて、土地改革を皮切りにさまざまな政策が行われたが、これらの政策は朝鮮に居住する華僑にも適用された。本稿では、第二次世界大戦後東アジアにおける冷戦体制の確立と朝鮮戦争、および1954年以降展開された朝鮮の協同化政策を切り口とし、これらの外的要因によって、近代開港期から続いた朝鮮華僑の職業形態が断絶を余儀なくされた過程について、中国側の档案資料と朝鮮華僑への訪問調査などを用いて明らかにしている。After World War Ⅱ,North Korea has implemented a series of economic policies aimed at socialist development, including land reform that have influenced the Overseas Chinese in North Korea. This paper focuses on the analysis of the Cold War pattern gradually set up in East Asia after World War Ⅱ, the Korean War, and the cooperation policy implemented in North Korea from 1954, based on relevant archives in China and interviews with North Korean Overseas Chinese returnees, to study the discontinuity of the occupation form of the Overseas Chinese in North Korea due to external economic and political changes after North Korea opened its doors in modern times

Fortuitous somatic mutations during antibody evolution endow broad neutralization against SARS-CoV-2 Omicron variants

Summary: Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency