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Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±8.4 µm measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments.

Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5 plus or minus 8.4 mu m measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments.

Massive XML data are increasingly generated for the representation, storage and exchange of web information. Twig query processing over massive XML data has become a research focus. However, most traditional algorithms cannot be directly implemented in a distributed manner. Some of the existing distributed algorithms generate a lot of useless intermediate results and execute many join operations of partial results in most cases; others require the priori knowledge of query pattern before XML partition, storage and query processing, which is impractical in the cases of large-scale data or frequent incoming new queries. To improve efficiency and scalability, in this paper, we propose a 3-phase distributed algorithm DisT3 based on node distribution mechanism to avoid unnecessary intermediate results. Furthermore, we propose a lightweight local index ReP with an enhanced XML partitioning approach using arbitrary partitioning strategy, and based on ReP we propose an improved 2-phase distributed algorithm DisT2ReP to further reduce the communication cost. After the performance guarantees are analyzed, extensive experiments are conducted to verify the efficiency and scalability of our proposed algorithms in distributed twig query applications.

Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells （iPSCs） harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells （NSCs） or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clari the molecular mechanisms of neurological abnormalities in the XP patients.

Chronic myeloid leukemia （CML） is a clonal hemato poietic stem cell disorder characterized by the oncogenic BCR-ABL fusion gene with increased ABL tyrosine ki- nase （TK） activity [1]. Transduction of primitive hematopoietic cells with the BCR-ABL oncoprotein creates cells that display many features of their BCR-ABL＋ coun- terparts in CML patients. Inhibition of the TK activity of BCR-ABL by small molecule inhibitors （imatinib mesyl- ate （IM）, dasatinib and nilotinib） [2] causes impressive responses in chronic phase CML patients. Nevertheless, response failures, early relapses and the later emergence of IM-resistant disease remain significant problems for many patients. In particular, CML stem cells are insensi- tive to IM and other ABL inhibitors and are not eradi- cated by currently available agents [1, 3]. These findings underscore the importance of understanding the biology of CML stem/progenitor cells and their unique properties in vivo, in guiding the development of strategies to per- manently cure CML. We have used a new xenograft model that exploits the advantages of a long-living, large animal host, the goat, which can be transplanted in a preimmune state in utero and then followed for several years after birth [4]. We transplanted fetal goats in utero with BCR-ABL- transduced lin-CD34＋ human cord blood （CB） cells and analyzed 6 liveborn goats for persistent engraftment of GFP＋BCR-ABL＋ cells in multiple tissues and for initia- tion of early phase CML. Twenty-eight fetuses were injected intraperitoneally at 45-55 days of gestation with 2 x l04 to l0s transduced lin human CB cells （-85% were CD34＋, 20%-30% were GFP＋BCR-ABL＋）. Another 14 fetuses were similarly transplanted with control GFP- vector-transduced cells （MIG）. Both groups displayed a high rate of abortion （〉 50%）. Therefore, only 6 goats transplanted with BCR-ABL-transduced cells （all recipi- ents of 2 x 104 cells, hereafter referred to as BCR-ABL goats for brevity） and 5 goats transplanted with MIG-transduced cells （2-5 x 104 cells, hereafter referred to as MIG goats for brevity） were born alive and thus avail- able for follow-up studies. A group of 3 BCR-ABL goats and 2 MIG goats were sacrificed 3 weeks after birth. Fluorescence microscopy and confocal laser scanning microscopy revealed a large number of GFP＋ （BCR-ABL＋） cells in liver, kidney and lung from all three BCR-ABL goats （Supplementary in- formation, Figure S1A-S 1C）. FACS analysis also detect- ed GFP＋ （BCR-ABL＋） cells in suspensions prepared from multiple tissues including liver, kidney, smooth muscle, heart and lung of all three BCR-ABL goats （1%-49% of all the viable cells from these tissues, Supplementary information, Figure $2）. These results were confirmed by fluorescence in situ hybridization （FISH） analyses performed on cells isolated from the bone marrow （BM） or liver of a BCR-ABL goat using the P17H8 probe that specifically identifies the unique a-satellite DNA se- quences on human chromosome 17, and a specific probe for human BCR-ABL （Figure 1A and Supplementary information, Figure S3A）. Neither of these probes gave any signal in the control BM cells from a normal goat （unmanipulated） （Figure 1A）. Immunohistochemical staining of liver tissue sections obtained from all three of the 3-week-old BCR-ABL goats showed frequent coinci- dence of GFP fluorescence and the expression of human proliferating cell nuclear antigen （PCNA） （Supplementary information, Figure S1D）.Don A Baldwin

Biologics, including monoclonal antibodies （mAbs） and other therapeutic proteins such as cytokines and growth hormones, have unique characteristics compared to small molecules. This paper starts from an overview of the pharmacokinetics （PK） of biologics from a mechanistic perspective, the determination of a starting dose for first-in-human （FIH） studies, and dosing regimen optimisation for phase II/III clinical trials. Subsequently, typical clinical pharmacology issues alongthe corresponding pathways for biologics development are summarised, including drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific populations. The relationships between the molecular structure of biologics, their pharmacokinetic and pharmacodynamic characteristics, and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram.

Metal ions are involved in Aβ aggregate deposition and neurotoxicity via various processes, including acceleration of Aβ aggregation, disruption of normal metal homeostasis, and formation of reactive oxygen species （ROS）. Although metal chelation is a promising therapeutic strategy for Alzheimer＇s disease （AD）, the widespread use of chelation therapy faces a significant problem; namely, it is difficult to differentiate toxic metals associated with Aβ plaques from those required by normal metal homeostasis. Furthermore, the multifactorial nature of AD and the current lack of an accepted unitary theory to account for AD neurodegeneration also restrict AD treatment through a single therapeutic strategy. This paper presents a novel bifunctional platform by integrating nonpharmacological and pharmacological cues into one system for AD treatment. This electrically responsive drug release platform, based on conducting polymer polypyrrole （PPy） incorporated with graphene-mesoporous silica nanohybrids （GSN） nanoreserviors, could realize on-demand controlled drug delivery with spatial and temporal control. Electrochemical stimulation can treat peripheral nerve injury （PNI） to stimulate neurite outgrowth. This novel system can also effectively inhibit Aβ aggregate formation, decrease cellular ROS, and protect cells from Aβ-related toxicity. The purpose of this research is to promote the design of noninvasive remote-controlled multifunctional systems for AD treatment.

The separations of single-wall carbon nanotubes on length by sepharose gel were investigated in this work. The solutions of sodium dodecyl sulfate and sodium deoxycholate were applied as the eluent in sequence. SEM and Raman were used to char- acterize the length of nanotube bundles. The results show that the longer nanotubes were eluted out first, and then the shorter tubes were followed by the sodium dodecyl sulfate. However, the separated order was totally reversed by the sodium deoxy- cholate. By this method, the process generated nanotube fractions not only were narrower in length distributions, but also could control the separation orders by changing the eluents. Moreover, the separation principle was also discussed.

The entanglement dynamics of a two-qutrit system under decoherence from a spin environment is investigated by using negativityas entanglement measure. Our results imply that the entanglement evolution depends not only on the coupling strength and thetunneling elements of the environment but also on the number of the freedom degrees and the initial state of the environment.

Aims Grain yields of summer maize are significantly affected by different nitrogen (N) rates and depths through regulating root growth and distribution in soil. Understanding of effects of the deep placement of N on the root and shoot growth, grain yield and N use efficiency in summer maize are limited. Methods In this study, four N rates: 225, 191.25, 157.5 and 0 kg ha −1 applied at four depths: 5, 10, 15, and 20 cm were studied. Soil N content, root dry weight, root length density, biomass, grain yield and N use efficiency of maize were measured. Results Compared to 225 kg N ha −1 applied at a depth of 5 cm, a 15% reduction in the N application rate at a depth of 15 cm induced a larger root length density in the subsoil, as well as a larger rooting depth. It also facilitated maintaining a higher level of biomass and N accumulation during the later growth period, which increased the N assimilation of grain and enhanced grain yield by 3.9%, N recovery efficiency by 66.7%, N agronomic efficiency by 38.5%, and partial factor productivity of N by 22.1%. Conclusions Overall, this study demonstrates that reducing the recommended N application rate of 225 kg ha −1 by 15% but applying it at a depth of 15 cm might be considered an efficient fertilization method that increases agricultural productivity and N use efficiency.