Naphthalimides, such as amonafide and mitonafide in clinical trials, have been developed as antitumor agents for orthotopic tumor. However, the serious side effects in cancer patients limit their applications. Herein, a new class of polyamine-based naphthalimide conjugates 5a-5c, 7a-7b, and 11a-11b with and without the alkylation of the distant nitrogen in the polyamine chain were synthesized and the mechanism was determined. Compared with amonafide, dinitro-naphthalimide conjugate 5c with a 4,3-cyclopropyl motif preferentially accumulates in cancer cells and minimizes side effects in vitro and in vivo. More importantly, 5c at the dosage of as low as 3 mg/kg (57.97%) displays better antitumor effects than the positive control amonafide (53.27%) at 5 mg/kg in vivo. And a remarkably elevated antitumor activity and a reduced toxicity are also observed for 5c at 5 mg/kg (65.90%). The upregulated p53 and the apoptotic cells (73.50%) indicate that the mechanism of 5c to induce apoptosis may result from its enhanced DNA damage. Further investigation indicates that in addition to target DNA, 5c can modulate the polyamine homeostasis by upregulating polyamine oxidase (PAO) in a different way from that of amonafide. And also by targeting PTs overexpressed in most of cancer cells, 5c downregulates the contents of Put, Spd, and Spm, which are in favor of suppressing fast-growing tumor cells. Our study implies a promising strategy for naphthalimide conjugates to treat hepatic carcinoma with notable activities and reduced toxicities at a low dosage. Copyright © 2020 Ma, Li, Li, Yue, Liu, Wang, Xi, Shi, Zhao, Ma, Liu, Guo, Liu, Hou, Wang, Wang, Tian and Xie.Intense antibiotic consumption in Low- and Middle-Income Countries (LMICs) is fueled by critical gaps in laboratory infrastructure and entrenched syndromic management of infectious syndromes. Few data inform the achievability and impact of antimicrobial stewardship interventions, particularly in Sub-Saharan Africa. Our goal was to demonstrate the feasibility of a pharmacist-led laboratory-supported intervention at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on antimicrobial use and clinical outcomes associated with the intervention. Methods This was a single-center prospective quasi-experimental study conducted in two phases (i) an intervention phase (November 2017 to August 2018), during which we implemented weekly audit and immediate (verbal and written) feedback sessions on antibiotic prescriptions of patients admitted in 2 pediatric and 2 adult medicine wards, and (ii) a post-intervention phase (September 2018 to January 2019) during which we audited antibiotic prescriptions bue, Libman, Gedif Fenta, Yansouni and Semret.Understanding reciprocal relationships between specific arenas in life and at work is critical for designing interventions to improve workplace health and safety. Most studies about the links between dimensions of well-being in life and at work have been cross-sectional and usually narrowly focused on one of the dimensions of the work-life well-being link. The issues of causality and feedback between life and work well-being have often not been addressed. We overcome these issues by measuring six aspects of well-being for both the work arena and life in general, using longitudinal data with a clear temporal sequence of cause and effect, and by explicitly accounting for feedback with potential effects in both directions. Nine hundred and fifty-four Mexican apparel factory workers at a major global brand participated in two waves of the Worker Well-Being Survey. Data on life satisfaction and job satisfaction, happiness and positive affect, meaning and purpose, health, and social relationships in life and at wors from this study may facilitate the development of novel workplace programs promoting working conditions that enable lifelong flourishing in life and at work. Copyright © 2020 Weziak-Bialowolska, Bialowolski, Sacco, VanderWeele and McNeely.Background X-linked Alport syndrome is caused by mutations in the COL4A5 gene, which encodes the a5(IV) chain. No mutations were detected in COL4A5 exons 41A and 41B. Materials and Methods A Chinese family with suspected Alport syndrome was enrolled in the present study to establish a precise diagnosis. The proband's father and uncle progressed to end-stage renal failure at different age. The indirect immunofluorescence method was used for analysis of distribution of a1 (IV) and a5 (IV) chains in the epidermal basement membrane from the father of the proband. The entire coding region of COL4A5 mRNA from the proband's father cultured skin fibroblasts was analyzed by using reverse-transcription polymerase chain reaction (RT-PCR) and direct sequencing, and genomic DNA was analyzed by using PCR and direct sequencing. To examine whether the alternatively COL4A5 mRNA transcripts existed in cultured skin fibroblasts, a fragment of COL4A5 cDNA, including exons 41A, 41B, and partial sequences of exons 41 and 42 was annal spectrum of X-linked Alport syndrome. In addition, skin tissue has three distinct COL4A5 transcripts with a diversity of expression. Copyright © 2020 Wang, Zhao, Ding and Li.Introduction Malignant brain tumors in infants less than 12 months of age are extremely rare, and they have poor prognosis. We evaluated genetic characteristics and response rates of infants with congenital brain tumors subjected to high-dose chemotherapy and autologous stem cell transplant after gross total tumor resection. Materials and Methods In total, 10 infants, aged less than 12 months, were enrolled in this study. The median age was 56 days (range 1-279 days). Pathological examination demonstrated the following four anaplastic astrocytomas, two glioblastomas, two central nervous system (CNS) embryonal tumors, not otherwise specified (NOS), and two atypical teratoid/rhabdoid tumors. https://www.selleckchem.com/products/wz-811.html Results All patients were exposed to induction chemotherapy regimen, two high-dose chemotherapy courses, and autologous stem cell transplant after maximal surgery. At 1-3-5 years, the global overall survival (OS) was 90, 70, and 70% and the progression-free survival (PFS) was 80-60 and 60%. In all the patients, the copy number variants (CNVs) profile was analyzed using the SNP/CGH array approach.