Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine. However, genetic manipulation and technically challenging strategies such as nuclear transfer used in reprogramming limit their clinical applications. Here, we show that pluripotent stem cells can be generated from mouse somatic cells at a frequency up to 0.2% using a combination of seven small-molecule compounds. The chemically induced pluripotent stem cells resemble embryonic stem cells in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. By using small molecules, exogenous "master genes" are dispensable for cell fate reprogramming. This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.
Colloidal semiconductor nanocrystals have been exploited in several applications in which they serve as fluorophores, because of the tunability of the wavelength of the emitted light.  The possibility of exactly controlling the size of nanocrystals is of great importance in the development of these materials, as this will lead to nano-objects with well-defined and reproducible properties. Whereas this goal seems to be hard to achieve with large nanocrystals, it might be viable for clusters consisting of a few tens or hundreds of atoms, as in this size regime a handful of structures can have an exceptionally high stability and therefore would form preferentially over any other combination of atoms. This concept is already well-known for several metal clusters, as for some of them several "magic" structures exist that are formed by closed shells of atoms.  Cluster molecules that can be considered as the smallest building units of semiconductors have been investigated in the past.As an example several tetrahedral cluster molecules based on the general formula [z-(where E = S or Se; M = Zn or Cd; and R = alkyl or aryl) or similar were reported some years ago. [8,9] The series was formed only by clusters containing a well-defined number of atoms, and therefore, characterized by particularly stable structures; thus, these structures can also be termed "magic-size clusters" (MSCs). Different families of almost monodisperse CdS clusters of sizes down to 1.3 nm were reported by Vossmeyer et al.,  whereas CdSe MSCs were observed later in the solution growth of colloidal nanocrystals  and the various cluster sizes found were explained as arising from the aggregation of smaller clusters. Soloviev et al. synthesized and crystallized a homologous series of CdSe cluster molecules [12,13] (very similar in structure to those reported earlier [8,9] ) that were capped by selenophenol ligands. Also in many high-temperature organometallic syntheses of colloidal CdSe nanocrystals, either the transient formation of ultrasmall, highly stable CdSe clusters was noticed, [14,15] or these clusters could be isolated using size-selective precipitation. [16,17] Recently, one type of CdSe MSC has been synthesized in a water-in-oil reverse-micelle system.Here, we report a method for controlling the sequential growth in solution of CdSe MSCs of progressively larger sizes. Each of these types of clusters is characterized by a sharp optical-absorption feature at a well-defined energy. During the synthesis, the relative populations of the different families of MSCs varied, as smaller MSCs evolved into larger MSCs. We can model the time evolution of the concentration of the various magic sizes using a modification of a continuous-growth model, by taking into account the much higher stability of the various MSCs over nanocrystals of any intermediate size.For the synthesis of the CdSe MSCs reported here a mixture of dodecylamine and nonanoic acid was used to decompose cadmium oxide at 200°C under an inert atmosphere. Th...
This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.
We report a general synthetic approach to tetrapod-shaped colloidal nanocrystals made of various combinations of II-VI semiconductors. Uniform tetrapods were prepared using preformed seeds in the sphalerite structure, onto which arms were grown by coinjection of the seeds and chemical precursors into a hot mixture of surfactants. By this approach, a wide variety of core materials could be chosen (in practice, most of the II-VI semiconductors that could be prepared in the sphalerite phase, namely, CdSe, ZnTe, CdTe); in contrast, the best materials for arm growth were CdS and CdTe. The samples were extensively characterized with the aid of several techniques.
The introduction of four transcription factors Oct4, Klf4, Sox2 and c-Myc by viral transduction can induce reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), but the use of iPSCs is hindered by the use of viral delivery systems. Chemical-induced reprogramming offers a novel approach to generating iPSCs without any viral vector-based genetic modification. Previous reports showed that several small molecules could replace some of the reprogramming factors although at least two transcription factors, Oct4 and Klf4, are still required to generate iPSCs from mouse embryonic fibroblasts. Here, we identify a specific chemical combination, which is sufficient to permit reprogramming from mouse embryonic and adult fibroblasts in the presence of a single transcription factor, Oct4, within 20 days, replacing Sox2, Klf4 and c-Myc. The iPSCs generated using this treatment resembled mouse embryonic stem cells in terms of global gene expression profile, epigenetic status and pluripotency both in vitro and in vivo. We also found that 8 days of Oct4 induction was sufficient to enable Oct4-induced reprogramming in the presence of the small molecules, which suggests that reprogramming was initiated within the first 8 days and was independent of continuous exogenous Oct4 expression. These discoveries will aid in the future generation of iPSCs without genetic modification, as well as elucidating the molecular mechanisms that underlie the reprogramming process.
Hepatitis C virus (HCV) is a global challenge to public health. Several factors have been proven to be critical for HCV entry, including the newly identified claudin-1 (CLDN1). However, the mechanism of HCV entry is still obscure. Presently, among the 20 members of the claudin family identified in humans so far, CLDN1 has been the only member shown to be necessary for HCV entry. Recently, we discovered that Bel7402, an HCV-permissive cell line, does not express CLDN1 but expresses other members of claudin family. Among these claudins, CLDN9 was able to mediate HCV entry just as efficiently as CLDN1. We then examined if other members of the claudin family could mediate entry. We show that CLDN6 and CLDN9, but not CLDN2, CLDN3, CLDN4, CLDN7, CLDN11, CLDN12, CLDN15, CLDN17, and CLDN23, were able to mediate the entry of HCV into target cells. We found that CLDN6 and CLDN9 are expressed in the liver, the primary site of HCV replication. We also showed that CLDN6 and CLDN9, but not CLDN1, are expressed in peripheral blood mononuclear cells, an additional site of HCV replication. Through sequence comparison and mutagenesis studies, we show that residues N38 and V45 in the first extracellular loop (EL1) of CLDN9 are necessary for HCV entry.Hepatitis C virus (HCV) is the major cause of liver cirrhosis and hepatocellular carcinoma worldwide. Approximately 3% of the global population is infected with HCV, and at least 70% develop chronic hepatitis (13,17,32). In patients with chronic HCV infection, about 20% develop liver cirrhosis, about 5% of which go on to develop hepatocellular carcinoma (17). While HCV is generally confined to the liver, there is growing evidence suggesting that HCV can replicate in extrahepatic tissues including peripheral blood mononuclear cells (PBMCs) (4,15,23,24
Light-emitting devices (LEDs) based on colloidal inorganic semiconductor nanocrystals (quantum dots, QDs) represent a completely new technology platform for the development of flat-panel displays and flat-panel lighting systems. Their major advantages are the easy tuning of the saturated color emission across the visible-near-IR range and the high chemical and optical stability of the nanocrystal composites. These characteristics open the way to a new class of hybrid devices in which the low-cost, flexible technology of organic LEDs is combined with the long operating lifetime of inorganic semiconductor devices. In the work reported here, we demonstrate the first hybrid white-LED whose emission originates only from the ternary nanocrystal composites, with luminance performances matching the requirements of the lighting industry. Bright white-light emission is obtained from ternary QD composites by controlling the Förster energy transfer and chargetrapping mechanisms between the different components. The proposed approach provides a new general method for the fabrication of stable white-LEDs with a potentially long lifetime.All-organic white-LEDs have been investigated for their potential applications in the lighting industry and backlighting applications in displays.  The main advantages of organic technology for white-light generation with respect to other competing technologies, such as GaN-based devices,  lie in the possibility of fabricating large-area, perhaps flexible, lightemitting panels by low-cost fabrication techniques, such as evaporation and spin-casting.  Inorganic LEDs are, in fact, intrinsically point sources requiring complicated and expensive technological processes when integration in diffuse sources is required. To obtain white light from organic systems, different approaches are commonly used, namely, evaporation or co-evaporation of multilayer structures,  spincasting of different light-emitting compounds in a single active-layer structure, [10,11] exploitation of exciplex emission,  and, recently, the synthesis of single white-light-emitting molecules.  However, in most of these approaches, the purity of the color emission is strongly affected by the different aging rates of the active compounds. [7,8] In addition, device lifetimes are short, owing to heating, at the high luminance values required for lighting applications (>1000 cd m -2). In this scenario the integration of QDs into organic LEDs has the potential to overcome most of these problems, and it turns out to be a rich field of scientific endeavor.  The broadly tunable, saturated-color emission performance of QDs is unsurpassed by any class of organic chromophores. Furthermore, the environmental stability of covalently bonded inorganic nanocrystals is expected to increase the device lifetimes at the high luminance/current regimes required for lighting. Moreover, the high quantum yield and narrow band emission of QDs satisfy the technological requirements o...
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