Growing up different in Neolithic China: A contextualised case study and differential diagnosis of a young adult with skeletal dysplasia.

This paper presents a case study of a young adult from the late Neolithic Yangshao cultural period site (∼3300-2900 years BC) of Guanjia () located in Henan Province on the Central Plains of China, who has evidence for skeletal dysplasia characterised by proportional stunting of the long bones and a small axial skeleton, generalised osteopenia, and non-fusion of epiphyses. We provide a detailed differential diagnosis of skeletal dysplasia with paediatric onset and conclude that this is likely a form of hypopituitarism or hypothyroidism, an extremely rare finding within the archaeological context. This paper highlights the issues of distinguishing the forms of proportional dwarfism in palaeopathology because of the considerable variation in manifestation of these conditions. Finally, we assess whether there were any health and social implications for this person and community through the consideration of a bioarchaeology of care approach across the lifecourse, burial context, and information on social perceptions of 'difference' in the community. ：： （3300～2900）。，，，，。，，。。，。，、、""，。.

What's that big thing on your head? Diagnosis of a large frontoparietal lesion on an Eastern Zhou skull from Henan, China.

We carried out a differential diagnosis of a large frontoparietal lesion on a human skull from a Late Bronze Age archaeological site located on the Central Plain of China, dating to between 771 and 476 BC. The head of this individual was covered in cinnabar, a mercury-based pigment that later was used for medicinal purposes in China. The lesion was well-circumscribed and involved the outer and inner tables of the skull, slight diploë thickening, and coarsening of bone trabeculae with expansion of intertrabecular spaces. We show that the observed changes are most consistent with cavernous hemangioma of the skull, a benign vascular malformation that preferentially affects older adults. Hemangiomas are often neglected in the paleopathological literature because of their benign nature - they tend to be asymptomatic and do not affect quality of life to a significant degree. Nevertheless, they produce characteristic lesions that can be confused with several other conditions with unrelated etiologies, including congenital hemoglabinopathies, traumas, malignant or benign neoplasms, and Paget's disease. We outline the diagnostic criteria that distinguish cavernous hemangioma from other conditions affecting the skull.

Non-NAD-Like poly(ADP-Ribose) Polymerase-1 Inhibitors effectively Eliminate Cancer in vivo.

The clinical potential of PARP-1 inhibitors has been recognized >10years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problem for their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors. The majority of PARP-1 inhibitors known to date have been developed as NAD competitors. NAD is utilized by many enzymes other than PARP-1, resulting in a trade-off trap between their specificity and efficacy. To circumvent this problem, we have developed a new strategy to blindly screen a small molecule library for PARP-1 inhibitors by targeting a highly specific rout of its activation. Based on this screen, we present a collection of PARP-1 inhibitors and provide their structural classification. In addition to compounds that show structural similarity to NAD or known PARP-1 inhibitors, the screen identified structurally new non-NAD-like inhibitors that block PARP-1 activity in cancer cells with greater efficacy and potency than classical PARP-1 inhibitors currently used in clinic. These non-NAD-like PARP-1 inhibitors are effective against several types of human cancer xenografts, including kidney, prostate, and breast tumors in vivo. Our pre-clinical testing of these inhibitors using laboratory animals has established a strong foundation for advancing the new inhibitors to clinical trials.