Modern sugarcane cultivars (Saccharum spp.) are high polyploids, aneuploids (2n = ~12x = ~120) derived from interspecific hybridizations between the domesticated sweet species Saccharum officinarum and the wild species S. spontaneum. To analyse the architecture and origin of such a complex genome, we analysed the sequences of all 12 hom(oe)ologous haplotypes (BAC clones) from two distinct genomic regions of a typical modern cultivar, as well as the corresponding sequence in Miscanthus sinense and Sorghum bicolor, and monitored their distribution among representatives of the Saccharum genus. The diversity observed among haplotypes suggested the existence of three founding genomes (A, B, C) in modern cultivars, which diverged between 0.8 and 1.3 Mya. Two genomes (A, B) were contributed by S. officinarum; these were also found in its wild presumed ancestor S. robustum, and one genome (C) was contributed by S. spontaneum. These results suggest that S. officinarum and S. robustum are derived from interspecifserved in Saccharum. https://www.selleckchem.com/products/eht-1864.html It represents a major revision of the understanding of Saccharum diversity.Social workers have been critical in the response to HIV from its inception, in HIV prevention, support, and advocacy for stigmatized populations including gay, bisexual, and other men who have sex with men (GBM). Recently, social workers have been tasked with working in an era of increasingly biomedicalized HIV prevention, including pre-exposure prophylaxis (PrEP), a safe and highly effective new prevention technology. However, disparities in PrEP access due to structural barriers, including lack of health insurance coverage, and complex decision-making pathways and processes of engagement present substantial challenges for PrEP implementation. Ensuring equitable access to resources and supporting informed decision making are paramount to social work values, yet scant published literature has considered PrEP social work intervention. This article draws on qualitative data from 29 GBM respondents to highlight gaps in PrEP decision-making support and access that may be amenable to social work intervention. Authors describe opportunities for individual, interpersonal, organizational, and structural social work interventions to address multilevel gaps in PrEP implementation. Findings illuminate the complexity of individual experiences and social discourses regarding PrEP and their impact on GBM and raise important issues for social workers to consider in working with GBM clients, service providers, and administrators.PD-1 plays an important role as an immune checkpoint. Sintilimab is a newly approved PD-1 antibody for cancer immunotherapy with an unknown binding epitope on PD-1. In this study, to elucidate the molecular mechanism by which sintilimab blocks PD-1 activation, we applied Antibody binding epitope Mapping (AbMap) to identify the binding epitope of sintilimab. An epitope was successfully identified, i.e. SLAPKA, aa 127-132. By constructing a series of point mutations, the dominant residues S127, L128, A129, P130, and A132 of PD-1 were further validated by western blot analysis, biolayer interferometry, and flow cytometry. Structural analysis showed that the epitope is partially within the binding interface of PD-1 and PD-L1, and this epitope also partially overlaps with that of nivolumab and pembrolizumab. These results demonstrate that sintilimab can attenuate PD-1 activation by directly competing with the interaction between PD-1 and PD-L1 through binding with the key residues of the FG loop on PD-1. This study also demonstrates the high efficiency and accuracy of AbMap for determining the binding epitope of therapeutic antibodies.Neuroinflammation and cognitive decline are the key pathological features in aging that bring detrimental impacts upon quality of life. However, there is no effective anti-aging pharmacological therapy thus far. Dietary supplements in particular essence of chicken (EC) has been found to be an effective remedy for alleviating mental stress and improving memory. In addition, a novel hydrolyzed chicken extract, ProBeptigen/CMI-168 (PB), showed beneficial effects on cognitive ability. However, the antiaging effect and possible mechanism of PB and EC are still unknown. Here, we investigated the antiaging effects of PB and EC on hippocampus-related cognitive decline and neuroinflammation in aged mice. PB and EC were administered for 16 weeks in 10-month-old mice. Both PB and EC treatments ameliorated age-related deterioration of learning and memory, and attenuated oxidative stress and inflammation in the hippocampus. These results were associated with decreased inflammatory cytokine levels and increased neurotransmitter levels in the hippocampus. The overall effects of improving aging-induced cognitive decline were more robust in PB-treated mice, while EC was effective in decreasing oxidative stress and inflammation. Moreover, alterations in the diversity and composition of the gut microbiota in aged mice were also regulated by both PB and EC, which induced distinguished features in the gut microbiota and their related functions. This study showed that PB exerts neuroprotective effects in aged mice, the mechanism of which might be different from that of EC. Therefore, PB has a potential as dietary supplement for ameliorating cognitive dysfunction and neuroinflammation in elderly individuals. Ultrafine particles (UFPs) are generated from common work processes and have thus existed for a long time. Far more prevalent than engineered nanoparticles, they share common toxicological characteristics with them. However, there is no existing retrospective assessment tool specific to UFPs, for example, for epidemiological purposes. Thus, we aimed to develop a job-exposure matrix dedicated to UFPs. Fifty-seven work processes were identified as well as the chemical composition of UFPs emitted, following a literature review and the input of an expert panel. These work processes were associated with occupational codes as defined by the ISCO 1968 classification. The probability and frequency of UFP exposure were assessed for each combination of occupational code and process. Summarized probabilities and frequencies were then calculated for all ISCO occupational codes associated with several processes. Variations in exposure over time or across industrial sectors were accounted for in the assessment of each occupational code.