Healthy aging is a complex biological process with progressive accumulation of senescent cells characterized by stable cell cycle arrest, resulting in impaired homeostasis, regenerative potential, ...and gradual functional decline in multiple tissues and organs, whereby the aberrant activation of mammalian target of rapamycin (mTOR) signaling networks plays a central role. Herein, we explored the effects of extracellular vesicles (EVs) released by gingiva-derived mesenchymal stem cells (GMSC-EVs) on oxidative stress–induced cellular senescence in human endothelial cells and skin fibroblasts and their antiaging potentials. Our results showed that GMSC-EVs robustly abrogated oxidative stress–induced upregulation in the expression of cellular senescence-related genes, such as β-galactosidase, p21, p53, and γH2AX, and mTOR/pS6 signaling pathway, in human umbilical vein endothelial cells (HUVECs) and skin fibroblasts. Meanwhile, GMSC-EVs restored oxidative stress–induced impairment in proliferation and tube formation by HUVECs. Systemic administration of GMSC-EVs attenuated aging-associated elevation in the expression levels of p21, mTOR/pS6, interleukin 6, and tumor necrosis factor α in skin and heart tissues of aged mice. These findings suggest that GMSC-EVs could be a potential alternative source of cell-free product for attenuation of aging-related skin and vascular dysfunctions due to their potent inhibitory effects on oxidative stress–induced cellular senescence in endothelial cells and skin fibroblasts.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Summary
Background
Psoriasis is a chronic skin disorder that manifests as epidermal keratinocyte hyperplasia.
Objectives
We examined the effect of oxymatrine treatment on cell proliferation and ...apoptosis in skin lesions of psoriasis.
Patients and methods
Patients with severe plaque psoriasis were treated with oxymatrine or with acitretin. The skin lesions were stained with proliferating cell nuclear antigen (PCNA), Ki‐67 and Bcl‐2, as well as examined by terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL). We performed correlations of the Psoriasis Area and Severity Index (PASI) and the proliferation and apoptosis index.
Results
Oxymatrine significantly reduced the psoriasis lesions as demonstrated by the reduced PASI score after treatment 6·91; 95% confidence interval (CI) 5·00–8·81, P < 0·001. In the oxymatrine group, the mitotic index was 26·15 (95% CI 24·80–27·49) before oxymatrine treatment, decreasing to 14·52 (95% CI 13·82–15·25; P < 0·001) after treatment, but remained higher than the normal group (6·24; 95% CI 5·87–6·61, P < 0·001). Oxymatrine also inhibited the proliferation of epidermal cells in the skin lesion as indicated by the reduced proliferation index after treatment (P < 0·01). In addition, oxymatrine treatment reduced cellular apoptosis as shown by increased Bcl‐2 expression and a decrease in TUNEL‐positive cells. The PASI score was positively correlated with mitotic index, proliferation index and apoptotic index (TUNEL), but negatively correlated with Bcl‐2 expression.
Conclusions
Oxymatrine treatment reduced proliferation but inhibited apoptosis of cells in the skin lesion. The balance between cell proliferation and turnover may contribute to the significant alleviation of psoriasis by oxymatrine.
What's already known about this topic?
Psoriasis manifests as epidermal keratinocyte hyperplasia with proliferation, keratinocyte maturation and turnover rates.
Current drugs for psoriasis may inhibit cell proliferation but could not adjust the balance of cell division, differentiation and apoptosis.
What does this study add?
We studied the efficacy of oxymatrine in the treatment of psoriasis and analysed the correlation of skin lesions, proliferation and apoptosis index before and after oxymatrine treatment.
What is the translational message?
Our study has demonstrated that oxymatrine is effective in the treatment of severe plaque psoriasis.
It has comparable efficacy with acitretin.
Because acitretin treatment was sometimes associated with metabolic abnormalities, our study suggests oxymatrine therapy as an alternative treatment for psoriasis in the context of acitretin allergy or adverse reactions.
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Linked Comment: Groma. Br J Dermatol 2019; 181:891–892.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the ...intensity and time of pollen exposure on PiAR prevalence.
Methods
A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.
Results
A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).
Conclusion
Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The nearly continuous light curves with micromagnitude precision provided by the space mission Kepler are revolutionizing our view of pulsating stars. They have revealed a vast sea of low-amplitude ...pulsation modes that were undetectable from Earth. The long time base of Kepler light curves allows for the accurate determination of the frequencies and amplitudes of pulsation modes needed for in-depth asteroseismic modeling. However, for an asteroseismic study to be successful, the first estimates of stellar parameters need to be known and they cannot be derived from the Kepler photometry itself. The Kepler Input Catalog provides values for the effective temperature, surface gravity, and metallicity, but not always with sufficient accuracy. Moreover, information on the chemical composition and rotation rate is lacking. We are collecting low-resolution spectra for objects in the Kepler field of view with the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, Xinglong observatory, China). All of the requested fields have now been observed at least once. In this paper, we describe those observations and provide a useful database for the whole astronomical community.
Cascade (domino) reactions have an unparalleled ability to generate molecular complexity from relatively simple starting materials; these transformations are particularly appealing when multiple ...rings are forged during this process. In this tutorial review, we cover recent highlights in cascade polycyclizations as applied to natural product synthesis, including pericyclic, heteroatom-mediated, cationic, metal-catalyzed, organocatalytic, and radical sequences.
Cascade (domino) reactions have an unparalleled ability to generate molecular complexity from relatively simple starting materials; these transformations are particularly appealing when multiple rings are forged during this process.
This study was to investigate the synergistic antibacterial effect and inhibition of biofilm formation of nisin in combination with terpenes (carvacrol, cinnamaldehyde, citral and thymol) against ...Listeria monocytogenes. The bactericidal ranking of terpenes combined with nisin was carvacrol > cinnamaldehyde, citral > thymol. The minimum inhibitory concentration (MIC) of nisin and carvacrol when used together was determined to be 0·1563 mg ml−1 + 0·0195 mg ml−1 (nisin at MIC/2 + carvacrol at MIC/16). The addition of nisin at MIC/2 + carvacrol at MIC/2 caused more decrease in membrane potential than carvacrol or nisin at MIC individually. The decrease rates of hlyA and plcA gene expressions caused by nisin at MIC/2 + carvacrol at MIC/2 were significantly higher than those caused by carvacrol or nisin at MIC individually (P < 0·05). Nisin combined with carvacrol showed the highest inhibition activity to the formation of L. monocytogenes biofilm on stainless steel and lettuce. The inhibition effect of nisin at MIC/2 + carvacrol at MIC/16 was significantly higher than that of nisin at MIC/2 and carvacrol at MIC/16 (P < 0·05).
Significance and Impact of the Study: Terpenes as important natural antimicrobials are getting considerable attention in the food industry, but their application is limited because of undesirable flavour and taste. In our study, the inhibitory effects and inhibition of biofilm formation of carvacrol, cinnamaldehyde, citral and thymol against Listeria monocytogenes ATCC 19115 were investigated when they were used individually or combined with nisin. We have demonstrated that nisin in combination with carvacrol had the best synergistic antibacterial effect and ability to inhibit biofilm formation. These observations can contribute to the effective application of these antibacterials in the food industry.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A second-order phase transition is characterized by spontaneous symmetry breaking. The nature of the broken symmetry in the so-called "hidden-order" phase transition in the heavy-fermion compound ...URu(2)Si(2), at transition temperature T(h) = 17.5 K, has posed a long-standing mystery. We report the emergence of an in-plane anisotropy of the magnetic susceptibility below T(h), which breaks the four-fold rotational symmetry of the tetragonal URu(2)Si(2). Two-fold oscillations in the magnetic torque under in-plane field rotation were sensitively detected in small pure crystals. Our findings suggest that the hidden-order phase is an electronic "nematic" phase, a translationally invariant metallic phase with spontaneous breaking of rotational symmetry.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a protocol for haploidentical allo-HSCT ...that combines granulocyte-colony stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients, including 86 in high-risk group, underwent transplantation from haploidentical family donors. All patients achieved sustained, full donor chimerism. One hundred and eleven patients were alive in remission at a median of 682 (253-1502) days. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA disparity. Patients younger than 15 years had less grade III-IV acute GVHD than older patients (P=0.044). The 2-year probability of relapse was 12% for standard-risk disease and 39% for high-risk disease. The 2-year probability of leukemia-free survival (LFS) was 68% for standard-risk patients and 42% for high-risk patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS (P=0.0017). The results require confirmation and show that G-BM combined with PBSC from haploidentical family donors, without in vitro TCD, may be used as a good source of stem cells for allo-HSCT.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The timing of early human dispersal to Asia is a central issue in the study of human evolution. Excavations in predominantly lacustrine sediments at Majuangou, Nihewan basin, north China, uncovered ...four layers of indisputable hominin stone tools. Here we report magnetostratigraphic results that constrain the age of the four artefact layers to an interval of nearly 340,000 yr between the Olduvai subchron and the Cobb Mountain event. The lowest layer, about 1.66 million years old (Myr), provides the oldest record of stone-tool processing of animal tissues in east Asia. The highest layer, at about 1.32 Myr, correlates with the stone tool layer at Xiaochangliang, previously considered the oldest archaeological site in this region. The findings at Majuangou indicate that the oldest known human presence in northeast Asia at 40° N is only slightly younger than that in western Asia. This result implies that a long yet rapid migration from Africa, possibly initiated during a phase of warm climate, enabled early human populations to inhabit northern latitudes of east Asia over a prolonged period.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► We examined how land use changes affect streamflow and sediment. ► Farmland, forest and urban areas are the strongest contributors to streamflow change. ► Farmland and forest also contribute to ...changes in sediment yield. ► PLSR is a practicable methodology and can eliminate variable co-linearity.
Understanding how changes in individual land use types influence the dynamics of streamflow and sediment yield would greatly improve the predictability of the hydrological consequences of land use changes and could thus help stakeholders to make better decisions. Multivariate statistics are commonly used to compare individual land use types to control the dynamics of streamflow or sediment yields. However, one issue with the use of conventional statistical methods to address relationships between land use types and streamflow or sediment yield is multicollinearity. In this study, an integrated approach involving hydrological modelling and partial least squares regression (PLSR) was used to quantify the contributions of changes in individual land use types to changes in streamflow and sediment yield. In a case study, hydrological modelling was conducted using land use maps from four time periods (1978, 1987, 1999, and 2007) for the Upper Du watershed (8973km2) in China using the Soil and Water Assessment Tool (SWAT). Changes in streamflow and sediment yield across the two simulations conducted using the land use maps from 2007 to 1978 were found to be related to land use changes according to a PLSR, which was used to quantify the effect of this influence at the sub-basin scale. The major land use changes that affected streamflow in the studied catchment areas were related to changes in the farmland, forest and urban areas between 1978 and 2007; the corresponding regression coefficients were 0.232, −0.147 and 1.256, respectively, and the Variable Influence on Projection (VIP) was greater than 1. The dominant first-order factors affecting the changes in sediment yield in our study were: farmland (the VIP and regression coefficient were 1.762 and 14.343, respectively) and forest (the VIP and regression coefficient were 1.517 and −7.746, respectively). The PLSR methodology presented in this paper is beneficial and novel, as it partially eliminates the co-dependency of the variables and facilitates a more unbiased view of the contribution of the changes in individual land use types to changes in streamflow and sediment yield. This practicable and simple approach could be applied to a variety of other watersheds for which time-sequenced digital land use maps are available.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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