Search

Stem cell senescence and depletion are major causes of aging and aging-related diseases. The NAD (Nicotinamide adenine dinucleotide) – SIRT1 (Silent Information Regulator 1) – PARP1 (Poly (ADP-ribose) polymerase-1) axis has gained interest owing to its significant role in regulating stem cell senescence and organismal aging. A recent study from our lab showed that pre-B-cell leukemia transcription factor1 (PBX1) overexpression attenuates hair follicle-derived mesenchymal stem cells (HF-MSCs) senescence and apoptosis by regulating ROS-mediated DNA damage via PARP1 downregulation; thus, suggesting that PARP1 downregulation is a common manifestation of the roles of both PBX1 and SIRT1 in HF-MSCs senescence attenuation, and implying a potential link between PBX1 and SIRT1. To this end, HF-MSCs overexpressing PBX1, overexpressing both PBX1 and PARP1, downregulating SIRT1, and overexpressing PBX1 as well as downregulating SIRT1 were generated, and senescence, apoptosis, DNA damage, and repair biomarkers were analyzed. Our results showed that (1) PBX1 overexpression alleviated HF-MSCs senescence and apoptosis accompanied by SIRT1 upregulation, PARP1 downregulation, and increased intracellular NAD and ATP levels. (2) SIRT1 knockdown enhanced cellular senescence and apoptosis, accompanied by increased ROS accumulation, DNA damage aggravation, and decreased intracellular NAD and ATP levels. (3) PBX1 overexpression rescued HF-MSCs senescence and apoptosis induced by SIRT1 knockdown. (4) PBX1 rescued PARP1 overexpression-mediated ATP and NAD depletion, accompanied by increased SIRT1 expression. Collectively, our results revealed that a positive interaction feedback loop exists between PBX1 and SIRT1. To the best of our knowledge we are the first to report that there is a PBX1-SIRT1-PARP1 axis that plays a critical role in alleviating HF-MSCs senescence and apoptosis. We provide a new perspective on the mechanisms underlying stem cell senescence as well as age-related disease prevention and treatment. Graphical Abstract

Hair follicles are easily accessible skin appendages that protect against cold and potential injuries. Hair follicles contain various pools of stem cells, such as epithelial, melanocyte, and mesenchymal stem cells (MSCs) that continuously self-renew, differentiate, regulate hair growth, and maintain skin homeostasis. Recently, MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential. In this review, we describe the applications of human hair follicle-derived MSCs (hHF-MSCs) in tissue engineering and regenerative medicine. We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail. We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages, including supplementation of growth factors, 3D suspension culture technology, and 3D aggregates of MSCs. In addition, we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels, regenerated hair follicles, induced red blood cells, and induced pluripotent stem cells. In summary, the abundance, convenient accessibility, and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.

To express a TAT-PBX1 fusion protein using a prokaryotic expression system and to explore potential effects of TAT-PBX1 in the proliferation and senescence of human hair follicle-derived mesenchymal stem cells. The TAT-PBX1 fusion was produced in inclusion bodies and heterogenously expressed in Rosetta (DE3) cells. Immunofluorescence staining showed that TAT-PBX1 fusion proteins were internalized by human hair follicle-derived mesenchymal stem cells. The growth rate of cells was increased after treatment with more than 5.0 μg/mL of TAT-PBX1. The rate of senescence-associated β-galactosidase positive cells was reduced in the 10.0 μg/mL TAT-PBX1 group (28%) than the 0 μg/mL control group (60%). Cells treated with the TAT-PBX1 fusion protein showed higher expression of p-AKT (1.22-fold that of the control), which indicates that TAT-PBX1 activated AKT pathway after cellular uptake. The TAT-PBX1 fusion protein increased the proliferation of hair follicle mesenchymal stem cells and delayed their senescence by activating the AKT pathway following internalization by cells.

Hair follicles (HFs) maintain homeostasis through the hair cycles; therefore, disrupting the hair cycle may lead to hair loss. Our previous study showed that apoptosis-inducing factor (AIF) nuclear translocation and poly [ADP-ribose] polymerase 1 (PARP1) upregulation induced apoptosis in mouse hair follicles during the hair cycle transition from anagen to catagen. However, the mechanism underlying this phenomenon remains unclear. In this study, we found that intrinsic ROS levels increased during the hair follicle cycle transition from anagen to catagen, followed by abrupt DNA breaks and activation of homologous recombinant and nonhomologous end joining DNA repair, along with the enhancement of apoptosis. Mice in different stages of the hair cycle were sacrificed, and the dorsal skins were collected. The results of western blot and histological staining indicated that AIF-PARP1 plays a key role in HF apoptosis, but their role in the regulation of the HF cycle is not clear. Mice were treated with inhibitors from anagen to catagen: treatment with BMN 673, a PARP1 inhibitor, increased DNA breaks and activated the cytochrome c/caspase-3-mediated apoptotic pathway, accelerating HF regression. Ac-DEVD-CHO (Ac), a caspase-3 inhibitor, attenuated HF degeneration by upregulating PARP1 expression, suggesting a seesaw relationship between cytochrome c-caspase-3- and AIF-PARP1-mediated apoptosis, wherein PARP1 may be the fulcrum. In addition, macrophages were involved in regulating the hair cycle, and the rate of M1 macrophages around HFs increased during catagen, while more M2 macrophages were found during anagen and telogen. Our results indicate that intrinsic ROS drive HF cycle progression through DNA damage and repair, followed by apoptosis. Intrinsic ROS drive hair follicle cycle progression by modulating DNA damage and repair, and consecutively, hair follicle apoptosis and macrophage polarization work together to promote the hair follicle cycle.

People are becoming less comfortable in content as a form of data throughout this period of growing scientific and technological advancements. Oil painting also was challenged in unprecedented ways by modern image processing techniques as person’s primary source of data, and it had a tremendous effect on the domain of artistic creativity. Therefore, we present an upgraded convolutional neural network (U-CNN) for the enhancement of style rendering model addressing the aforementioned challenges. Initially, the datasets are gathered that are denoised and enhanced in the preprocessing stage to eliminate noise and improve the quality of the data. Gabor filter bank (GFB) is employed in the feature extraction stage to extract several features from the normalized data. For the application of style rendering model, the proposed approach is utilized. Moreover, through applying the 3DS MAX model, the three-dimensional (3-D) oil painting is generated. Finally, the performance of the proposed approach is examined and compared with other existing approaches to obtain the proposed approach with the greatest effectiveness. The findings are depicted in chart form by employing the origin tool.

Rolling contact fatigue (RCF) failure is an important concern for wheel and rail system of railway transportation. In this work, the effect of non-uniform microstructure of the pearlite- ferrite wheel steel on RCF was investigated. Some bainite regions dispersedly distributed in the matrix of ferrite and pearlite. The hardness and chemical composition of different regions of wheel steel were determined by Vickers hardness tester and electron probe microanalysis (EPMA) respectively. As the hardness was different in these two regions, the initiation and propagation of cracks occurred at the boundary of abnormal microstructure mainly. EPMA results showed that the contents of Mn and Si were higher in positive segregation region than those of the matrix. In addition, the thermodynamic model was used to calculate the evolution of time-temperature-transformation (TTT) diagram of steel with element segregation. Result showed that the increase of Mn and Si in positive segregation region changed the shape of the TTT curves and caused the formation of abnormal microstructure.

The crashworthiness of embedded composite structures that couple carbon fiber reinforced plastic tubes and aluminum honeycomb (CFRP-AH) was assessed through quasi-static compression tests and finite element simulation. Experimental results show that CFRP tubes tilt, when the AH fits with the CFRP tubes is not tight enough. With an increasing number of embedded CFRP tubes, the CFRP-AH composite structures are found to have a larger mean crush force (MCF) and specific energy absorption (SEA). Among the four experimental groups, CFRP-AH composite structures in Group S3, which used a larger size of CFRP tube, are found to have significantly improved energy-absorbing performance, and SEA of S3-t25 is improved by 576% compared with that of the pure AH S3-t0 without tubes. The S2 group’s CFRP tube is tilted, which used a smaller size, and the structure is improved to obtain the NS2 structure, so that only tearing deformation occurs in the AH-CFRP structure’s CFRP tube. The SEA of NS2-t25 was improved by 29.70% over S2-t25 and 22.83% over S3-t25, which has the best energy absorption characteristics among the filled tube structures.

Motor babbling and goal babbling has been used for sensorimotor learning of highly redundant systems in soft robotics. Recent works in goal babbling have demonstrated successful learning of inverse kinematics (IK) on such systems, and suggest that babbling in the goal space better resolves motor redundancy by learning as few yet efficient sensorimotor mappings as possible. However, for musculoskeletal robot systems, motor redundancy can provide useful information to explain muscle activation patterns, thus the term motor abundance. In this work, we introduce some simple heuristics to empirically define the unknown goal space, and learn the IK of a 10 DoF musculoskeletal robot arm using directed goal babbling. We then further propose local online motor babbling guided by Covariance Matrix Adaptation Evolution Strategy (CMA-ES), which bootstraps on the goal babbling samples for initialization, such that motor abundance can be queried online for any static goal. Our approach leverages the resolving of redundancies and the efficient guided exploration of motor abundance in two stages of learning, allowing both kinematic accuracy and motor variability at the queried goal. The result shows that local online motor babbling guided by CMA-ES can efficiently explore motor abundance at queried goal positions on a musculoskeletal robot system and gives useful insights in terms of muscle stiffness and synergy., IEEE/RSJ International Conference on Intelligent Robots and Systems (iROS2019), November 4 - 8, 2019, Macau, China

Background PBX homeobox 1 (PBX1) is involved in the maintenance of the pluripotency of human embryonic and hematopoietic stem cells; however, the effects of PBX1 in the self-renewal and reprogramming of hair follicle mesenchymal stem cells (HF-MSCs) are unclear. The AKT/glycogen synthase kinase (GSK) 3β pathway regulates cell metabolism, proliferation, apoptosis, and reprogramming, and p16 and p21, which act downstream of this pathway, regulate cell proliferation, cell cycle, and apoptosis induced by reprogramming. Here, we aimed to elucidate the roles of PBX1 in regulating the proliferation and reprogramming of HF-MSCs. Methods A lentiviral vector designed to carry the PBX1 sequence or PBX1 short hairpin RNA sequence was used to overexpress or knock down PBX1. The roles of PBX1 in proliferation and apoptosis were investigated by flow cytometry. Real-time polymerase chain reaction was performed to evaluate pluripotent gene expression. Dual-luciferase reporter assays were performed to examine the transcriptional activity of the NANOG promoter. Western blotting was performed to identify the molecules downstream of PBX1 involved in proliferation and reprogramming. Caspase3 activity was detected to assess HF-MSC reprogramming. The phosphatidylinositol 3-kinase/AKT inhibitor LY294002 was used to inhibit the phosphorylation and activity of AKT. Results Overexpression of PBX1 in HF-MSCs increased the phosphorylation of AKT and nuclear translocation of β-catenin, resulting in the progression of the cell cycle from G0/G1 to S phase. Moreover, transfection with a combination of five transcription factors (SOMKP) in HF-MSCs enhanced the formation of alkaline phosphatase-stained colonies compared with that in HF-MSCs transfected with a combination of four transcription factors (SOMK). PBX1 upregulated Nanog transcription by activating the promoter and promoted the expression of endogenous SOX2 and OCT4. Furthermore, PBX1 expression activated the AKT/glycogen synthase kinase (GSK) 3β pathway and reduced apoptosis during the early stages of reprogramming. Inhibition of phospho-AKT or knockdown of PBX1 promoted mitochondrion-mediated apoptosis and reduced reprogramming efficiency. Conclusions PBX1 enhanced HF-MSC proliferation, and HF-MSCs induced pluripotent stem cells (iPSC) generation by activating the AKT/GSK3β signaling pathway. During the reprogramming of HF-MSCs into HF-iPSCs, PBX1 activated the NANOG promoter, upregulated NANOG, and inhibited mitochondrion-mediated apoptosis via the AKT/GSK3β pathway during the early stages of reprogramming.

The demand for continually improving the transient performance of diesel engines requires higher rail pressure and more efficient turbocharger. Before the test, a two-stage turbocharger with a turbine by-pass valve (TBV) had been matched reasonably with the base engine. In order to reduce smoke emission under the typical 5-second transient process of constant speed and increasing torque, the influence of rail pressure on combustion, emissions and performance characteristics was experimentally investigated. The results showed that the two-stage turbocharger was helpful in improving transient performance. Moreover, the full-stage rail pressure (FSRP) strategies (increasing rail pressure during the whole transient process) could reduce smoke emission when the TBV was closed. However, smoke deteriorated once TBV opening got larger. Then the sectional-stage rail pressure (SSRP) strategies (increasing rail pressure from a pre-set load to 100 % load) were presented under small TBV opening to improve in-cylinder thermal condition. Hence, the air-fuel mixing process was improved at medium and large loads. Then the maximum decline of smoke opacity peak was 56.3 %, which happened under 10 % TBV opening. In addition, fuel consumption of FSRP strategies got worse under larger TBV opening. However, this deterioration situation could be effectively restrained by the utilization of SSRP strategies.

Melanocytes are the major cells responsible for skin and fair pigmentation in vertebrates. They localize to hair follicles(HFs) and the epidermis during embryonic development. A reduced number or dysfunction of melanocytes results in pigmentation disorders.Thus, methods for isolation, culture, and identification of melanocytes in mouse hair follicles provide an experimental basis for thestudy of of pigmentation disorders. In the current work, we harvested the melanocytes from the anagen phase dorsal skin of C57BL/6 mice.After its separation from the skin, the dermis was digested, and the HFs were released. HFs were then also digested, and the cells released from HFs were cultured in melanocyte growth medium. Immunofluorescence and immunohistochemistry staining were used to localize the distribution of melanocytes in HFs . Reverse transcription polymerase chain reaction was performed to detect the expression of specific melanocyte marker genes. Immunofluorescence, immunohistochemistry, flow cytometry, and western blot were carried out to detect the expression of marker proteins in cells. 3,4-Dihydroxy-L-phenylalanine (L-DOPA) staining was used to detect the pigmentation functionality of melaonocytes. Based on our results, we conclude that mature and functional melanocytes can be successfully obtained from theHFs, providing a cell model to study pigmentation disorders. The current findings provide novel insights for the treatment of pigmentation disorders by autologous cell transplantation. Further, we believe that issues related to skin damage, insufficient numbers of autologous cells, and autoimmune problems can be resolved in future though the use of functional melanocytes.

Argon (Ar) is the third most common gas in the Earth’s atmosphere. About 700,000 tonnes of Ar are produced worldwide every year. Ar is inexpensive since it occurs naturally in air, and is readily obtained as a byproduct of cryogenic air separation in the production of O2 and N2. To decrease NOx emissions and slightly improve the thermal efficiency, Ar has been used in ICE before. However, it appears that it was used only in diesel and gasoline engines. This paper presents the effects of Ar dilution on the thermal efficiency and NOx emissions of a 6-cylinder natural gas SI engine. Ar was added into the intake charge at fixed boundaries under 1450 rpm and 50% load. The results show that the thermal efficiency increases first and then decreases with NOx emissions being decreased significantly as the dilution ratio (DR) of Ar increases. The thermal efficiency peaks at 9.8% DR with NOx emissions being decreased by 31.1%. At the maximum DR (18.4%), the thermal efficiency decreases by 0.3% with NOx emissions being decreased by 64.0%. Furthermore, from comparative experimental results it can be concluded that Ar dilution is superior in maintaining higher thermal efficiencies than CO2 and N2 for NG engines.

Particle number measurement is a new approach to determine emission, which may be more accurate at very low emission levels than when using gravimetric measurements. An experimental study was performed to investigate the effect of fuel properties on the performance, combustion process, regulated gaseous emissions and particle number emissions of a diesel engine with an uncatalyzed diesel particulate filter (DPF). The effect of the filter on the particle size distribution was reported. The DPF number-based filtration efficiency in terms of number efficiency and fractional efficiency for petroleum diesel fuel and two alternative fuels, BTL and GTL, were analyzed. For nearly all test modes, the filter had a higher number efficiency for diesel than for BTL and GTL. The DPF fractional efficiency showed it was highly dependent on fuel type and varied widely at each size range. For diesel, the filter fractional efficiency was sufficiently high and behaved as predicted by filtration theory. For BTL and GTL, the fractional performance of the filter decreased when unexpectedly low efficiencies within the nuclei mode were exhibited. This research will be helpful in understanding DPF number-based filtration performance for alternative fuels and will provide information for the development of particulate emission control technology.

Although investment has played an important role in China's phenomenal economic growth over the last two decades, there has been little research on investment determination at the macro level. This study sets out to explore and explain the factors that influence China's aggregate investment measured by the fixed capital formation during the reform period and to draw useful conclusions from analysing these determinants. The investigation is based on an assumption that aggregate investment in China is determined by both the cost of investment and the increasing aggregate demand created by the reforms. A dynamic investment function is developed to simultaneously capture the long-run and short-run properties of the investment behaviour. The empirical results based on a panel data set of 28 Chinese provinces and autonomous regions suggest that a homogenous equilibrium correction mechanism exists in China's aggregate investment process.

This paper studies the spatial differences of grain production efficiencies in China using a panel data set on 30 provinces (cities) for the period 1987–92. A stochastic frontier production function is estimated to derive the technical efficiencies across the regions. The results suggest that technical inefficiencies are significant with remarkable provincial and zonal differentials. The marginal productivities of factors and their convergence (divergence) over time, the decomposition of total factor productivity, and the effects of major determinants on technical inefficiencies are also studied in detail.

The agrarian system of China in the post-collective period is characterized by peasant subsistence and small-scale mixed family farms. Agricultural modernization requires rapid and sustained improvements in levels of output and productivity. Farm-level data of 7927 households sampled from two representative Chinese provinces allow us to formulate and estimate a stochastic frontier production function model that explains a considerable proportion of interfarm efficiency differences and quantifies the efficiency effects of farm size, access to credit, nutrition intake, education attainment, and farming experience. J. Comp. Econom., September 2000, 28(3), pp. 545–564. London Guildhall University, and Asian Development Bank and London School of Economics.

Airline deregulation in the USA was a rejection of inefficient regulation and inspired by the perspective of both potential and actual competition in the industry. Using multivariate regression and efficiency frontier techniques, the emergent structure of unregulated airline markets is assessed. Our findings, based on panel data for major US airlines during the period 1984–1991, indicate that (1) as a result of successful efforts by airlines to reduce the scope for competition, aviation technology now exhibits increasing rather than constant returns to network size as predicted by cost studies prior to deregulation; (2) deregulation failed to produce evidence of efficiency convergence among carriers as would be expected under sufficiently competitive conditions.

A stochastic frontier production function is used to investigate the prospect to bring China's grain production and productivity to higher levels using a panel data set on 30 provinces from 1987–92. Given an irreversible trend of declining agricultural land, the only feasible way to raise total grain output is to increase land productivity if China does not want to rely on large-scale imports to feed her huge and still growing population. Considerable regional differences in grain yields suggest that there is still a vast potential for raising grain output. The short term solution is to use more land-augmenting inputs such as fertilisers and irrigation in the medium and low yield regions. However, the law of diminishing returns is in operation as more physical inputs are applied to shrinking land. Growth in grain output in the long term must rely on improvements in technical efficiency.

China's phenomenal economic growth since 1979 is seen by many as a challenge to the belief that the clarification of property rights is a necessary step of successful transition from a planned economy to a market economy. Instead of mass and rapid privatization, reforms in the Chinese state industrial sector in the 1980s were attempted to reconstruct the incentive structure of enterprises by linking rewards to performance, expanding managerial freedom and exposing enterprises to market influences. This paper investigates the extent to which the partial reforms have transformed the behaviour and performance of state-owned enterprises (SOEs). Using a panel of observations on 769 SOEs from ten manufacturing industries during 1980 and 1989, a stochastic cost frontier function is estimated to measure the effect of various reform measures on both technical and allocative efficiency. We found that the average cost efficiency level increased by 1.18% per annum during the decade. The efficiency effects of the indu...

There has been renewed empirical work recently on testing the neoclassical model of economic growth using data on various groups of countries. But none of the cross-country regressions includes China, the largest developing economy in the world. This study utilises both cross-sectional and panel data on provinces of China over the reform period 1978–1995 to examine the extent to which the growth process in this country can be explained by the augmented Solow-Swan model. We found that in spite of restrictive assumptions used, the model provides a fairly good description of cross-sectional data. The levels and growth rates of GDP per capita are shown to be higher in regional economies with lower population growth, greater openness to foreign countries and more investment in physical and human capital. In addition, regional economies are shown to converge both conditionally and unconditionally over the reform period. However, the quantitative implications of the augmented Solow-Swan model are not borne out in panel data.

A stochastic frontier production function is used to estimate the effect of partial and gradual reforms in the 1980’s in each of seven state-owned manufacturing industries. Reform-induced gains in technical efficiency were significant in all sample industries although not always substantial enough to motivate industry-wide productivity growth. The bonus system had speedy and impressive efficiency effects, but there is no consistent evidence on the effectiveness of other reform measures, including greater output autonomy, partial exposure to market influences, and the possibility of dismissals for malfeasance. Equalization of marginal factor returns across firms was observed in some industries, which may be considered as evidence of improved allocative efficiency in response to the reforms.

International audience