To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54×10−10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36–1.82), and serine racemase (SRR) (P = 3.06×10−9; OR = 1.28; 95% CI = 1.18–1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65×10−10; OR = 1.29, 95% CI = 1.19–1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

Microscopy has greatly advanced our understanding of biology. Although significant progress has recently been made in optical microscopy to break the diffraction-limit barrier, reliance of such techniques on fluorescent labeling technologies prohibits quantitative 3D imaging of the entire contents of cells. Cryoelectron microscopy can image pleomorphic structures at a resolution of 3-5 nm, but is only applicable to thin or sectioned specimens. Here, we report quantitative 3D imaging of a whole, unstained cell at a resolution of 50-60 nm by X-ray diffraction microscopy. We identified the 3D morphology and structure of cellular organelles including cell wall, vacuole, endoplasmic reticulum, mitochondria, granules, nucleus, and nucleolus inside a yeast spore cell. Furthermore, we observed a 3D structure protruding from the reconstructed yeast spore, suggesting the spore germination process. Using cryogenic technologies, a 3D resolution of 5-10 nm should be achievable by X-ray diffraction microscopy. This work hence paves a way for quantitative 3D imaging of a wide range of biological specimens at nanometer-scale resolutions that are too thick for electron microscopy.coherent diffractive imaging | equally sloped tomography | lensless imaging | iterative phase-retrieval algorithms | oversampling A pplication of the long penetration depth of X-rays to the imaging of large, unstained biological specimens has long been recognized as a possible solution to the thickness restrictions of electron microscopy. Indeed, using sizable protein crystals, X-ray crystallography is currently the primary methodology used for determining the 3D structure of protein molecules at near-atomic or atomic resolution. However, many biological specimens such as whole cells, cellular organelles, some viruses, and many important protein molecules are difficult or impossible to crystallize and hence their structures are not accessible by crystallography. Overcoming these limitations requires the employment of different techniques. One promising approach currently under rapid development is coherent diffraction microscopy (also termed coherent diffractive imaging or lensless imaging) in which the coherent diffraction pattern of a noncrystalline specimen or a nanocrystal is measured and then directly phased to obtain an image (1-28). The well-known phase problem is solved by using the oversampling method (29) in combination with the iterative algorithms (30-33). Since its first experimental demonstration in 1999 (1), coherent diffraction microscopy has been applied to imaging a wide range of materials science and biological specimens such as nanoparticles, nanocrystals, biomaterials, cells, cellular organelles, viruses by using synchrotron radiation (2-21), high harmonic generation (22-24), soft X-ray laser sources (23, 25), and free electron lasers (26-28). Until now, however, the radiation damage problem and the difficulty of acquiring high-quality 3D diffraction patterns from individual whole cells have prevented the successful high-resolution ...

Decellularization is the process by which cells are discharged from tissues/organs, but all of the essential cues for cell preservation and homeostasis are retained in a three-dimensional structure of the organ and its extracellular matrix components. During tissue decellularization, maintenance of the native ultrastructure and composition of the extracellular matrix (ECM) is extremely acceptable. For recellularization, the scaffold/matrix is seeded with cells, the final goal being to form a practical organ. In this review, we focus on the biological properties of the ECM that remains when a variety of decellularization methods are used, comparing recellularization technologies, including bioreactor expansion for perfusion-based bioartificial organs, and we discuss cell sources. In the future, decellularization-recellularization procedures may solve the problem of organ assembly on demand.

Pioglitazone as a second-line treatment after metformin might provide a protective effect on dementia risk among individuals with type 2 diabetes.