Miracle-dz/UniFAR-FTUs huggingface dataset:
New insights into TGF-β/Smad signaling in tissue fibrosis.

Chronic kidney disease (CKD) has emerged as a major cause of morbidity and mortality worldwide. Interstitial ﬁ brosis, glomerulosclerosis and in ﬂ ammation play the central role in the pathogenesis and progression of CKD to end stage renal disease (ESRD). Transforming growth factor- β 1 (TGF- β 1) is the central mediator of renal ﬁ brosis and numerous studies have focused on inhibition of TGF- β 1 and its downstream targets for treatment of kidney disease. However, blockade of TGF- β 1 has not been e ﬀ ective in the treatment of CKD patients. This may be, in part due to anti-in ﬂ ammatory e ﬀ ect of TGF- β 1. The Smad signaling system plays a central role in regulation of TGF- β 1 and TGF- β /Smad pathway plays a key role in progressive renal injury and in ﬂ ammation. This review provides an overview of the role of TGF- β /Smad signaling pathway in the pathogenesis of renal ﬁ brosis and in ﬂ ammation and an e ﬀ ective target of anti- ﬁ brotic therapies. Under pathological conditions, Smad2 and Smad3 expression are upregulated, while Smad7 is downregulated. In addition to TGF- β 1, other pathogenic mediators such as angiotensin II and lipopolysaccharide activate Smad signaling through both TGF- β -dependent and in- dependent pathways. Smads also interact with other pathways including nuclear factor kappa B (NF- κ B) to regulate renal in ﬂ ammation and ﬁ brosis. In the context of renal ﬁ brosis and in ﬂ ammation, Smad3 exerts pro- ﬁ brotic e ﬀ ect, whereas Smad2 and Smad7 play renal protective roles. Smad4 performs its dual functions by transcriptionally promoting Smad3-dependent renal ﬁ brosis but simultaneously suppressing NF- κ B-mediated renal in ﬂ ammation via Smad7-dependent mechanism. Furthermore, TGF- β 1 induces Smad3 expression to regulate microRNAs and Smad ubiquitination regulatory factor (Smurf) to exert its pro- ﬁ brotic e ﬀ ect. In conclusion, TGF- β /Smad signaling is an important pathway that mediates renal ﬁ brosis and in ﬂ ammation. Thus, an e ﬀ ective anti- ﬁ brotic therapy via inhibition of Smad3 and upregulation of Smad7 signaling constitutes an attractive ap- proach for treatment of CKD.
THE MODULATION OF LYMPHOCYTE FUNCTIONS BY MOLECULES SECRETED BY MACROPHAGES

The basis of the experiments consisted of evaluating the incorporation of ['Hlthymi-dine of the cells cultured in medium containing various amounts of PEC culture fluids. The time of culture was always 72 h-pilot experiments indicated this to be the optimal time to see effects. All resultsare means of triplicate cultures expressed as counts per minute (cpm)plus or minus thevalue of one standard error of the mean. In some experiments we express the ratioof cpm of experimental and Cell
Discharge dependence of stream albedo in a steep proglacial channel

Stream surface albedo was measured at a location downstream of Place Glacier, Canada, in a steep bouldery channel. Portions of the water surface were visibly aerated as a result of the cascading flow even at lower discharges; at high flows, the stream was near‐continuous whitewater. Albedo generally increased with discharge, from around 0.1 at the lower flows to 0.4 at the highest flows. This increase is consistent with the known effect of aeration on the reflectance of water. This discharge dependence of albedo needs to be accounted for in physically based models for predicting stream temperature to avoid biased predictions of net radiation. For steep proglacial streams that experience decreasing late‐summer flows as a result of ongoing and future glacier recession, the associated decrease in albedo could promote higher stream temperatures, in addition to the effects of reduced flow depth and velocity. Copyright © 2011 John Wiley & Sons, Ltd.
[Revealing characteristics and rules of acupoint sensitization phenomena: based on knee osteoarthritis].

OBJECTIVE To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Methane production from global biomass burning

Emissions of methane from various sources of biomass burning are determined quantitatively for tropical, temperate, and boreal regions. About 85% of the total CH{sub 4} is emitted in the tropical area, which is mainly the result of shifting cultivation, fuelwood use, and deforestation. Methane emissions from biomass burning may have increased by at least 9% during the last decade because of increases in tropical deforestation and the use of fuelwood. Changes in land use practices and population growth in the tropics are possible causes of the increase of atmospheric CH{sub 4} concentration. 31 refs., 1 fig., 4 tabs.
Indocyanine Green-based Glow Nanoparticles Probe for Cancer Imaging

Indocyanine green (ICG) is one of the FDA-approved near infra-red fluorescent (NIRF) probes for cancer imaging and image-guided surgery in the clinical setting. However, the limitations of ICG include poor photostability, high concentration toxicity, short circulation time, and poor cancer cell specificity. To overcome these hurdles, we engineered a nanoconstruct composed of poly (vinyl pyrrolidone) (PVP)-indocyanine green that is cloaked self-assembled with tannic acid (termed as indocyanine green-based glow nanoparticles probe, ICG-Glow NPs) for the cancer cell/tissue-specific targeting. The self-assembled ICG-Glow NPs were confirmed by spherical nanoparticles formation (DLS and TEM) and spectral analyses. The NIRF imaging characteristic of ICG-Glow NPs was established by superior fluorescence counts on filter paper and chicken tissue. The ICG-Glow NPs exhibited excellent hemo and cellular compatibility with human red blood cells, kidney normal, pancreatic normal, and other cancer cell lines. An enhanced cancer-specific NIRF binding and imaging capability of ICG-Glow NPs was confirmed using different human cancer cell lines and human tumor tissues. Additionally, tumor-specific binding/accumulation of ICG-Glow NPs was confirmed in MDA-MB-231 xenograft mouse model. Collectively, these findings suggest that ICG-Glow NPs have great potential as a novel and safe NIRF imaging probe for cancer cell/tumor imaging. This can lead to a quicker cancer diagnosis facilitating precise disease detection and management.
Development of a Personalised Device for Systemic Magnetic Drug Targeting to Brain Tumours

Delivering therapies to deeply seated brain tumours (BT) is a major clinical challenge. Magnetic drug targeting (MDT) could overcome this by rapidly transporting magnetised drugs directly into BT. We have developed a magnetic device for application in murine BT models using an array of neodymium magnets with a combined strength of 0.7T. In a closed fluidic system, the magnetic device trapped magnetic nanoparticles (MNP) up to distances of 0.8cm. In mice, the magnetic device guided intravenously administered MNP (<50nm) from the circulation into the brain where they localised within mouse BT. Furthermore, MDT of magnetised Temozolomide (TMZmag+) significantly reduced tumour growth and extended mouse survival to 48 days compared to the other treatment groups. Using the same principles, we built a proof of principle scalable magnetic device for human use with a strength of 1.1T. This magnetic device demonstrated trapping of MNP undergoing flow at distances up to 5cm. MDT using our magnetic device provides an opportunity for targeted delivery of magnetised drugs to human BT.
Primary and Secondary Consolidation of Clay and Peat

Synopsis The dominant viscous mechanism governing the consolidation of the majority of clays and colloidal peats is described in terms of structural viscosity and thixotropy. A simple rheological model of an element of saturated clay is developed and solved for one-dimensional consolidation. The results give encouraging agreement with a wide range of published behaviour of clay and peat. The rheological model of the clay skeleton can be applied directly without integration in the case of partly-saturated clay with continuous air voids and provides a simple theoretical basis for predicting the compression-time behaviour. A consolidation mechanism relevant to fibrous peat involves the drainage of a system of micropores into a system of coarser channels. The basic physics of this process has not yet been established and no solution is offered in this case. Le mecanisme visqueux dominant qui regit la consolidation de la majorite des argiles et des tourbes colloidales est decrit par rapport a la viscosite de s.
MORPHOLOGIC RESPONSE OF SUBALPINE STREAMS TO TRANSBASIN FLOW DIVERSION 1

ABSTRACT: Flow has been diverted from Rocky Mountain streams for many years with little documentation of the impacts on physical form and biological function of the losing stream system. This study addresses whether differences in form can be detected in subalpine step‐pool, plane bed, or pool‐riffle channels and linked to changes in flow regime from diversion. Total annual discharge was reduced between 20 and 60 percent and average annual peak flow was reduced up to 45 percent in the subalpine systems assessed; channels were diverted between 20 and 100 years. Expected impacts include reduced conveyance and changes in vegetation growth patterns because formerly active surfaces are colonized by riparian species, effectuating shrinking channel capacity. In this study, reduced channel width is used as an indicator of morphologic response. Observed reductions in width, ranging from 35 to 50 percent at some sites, resulted not only from vegetation invasion of stable surfaces but also from the development of an inset beside former cut banks. This observation, however, was restricted to wider pool‐riffle channels with gravel bars. Outside of these areas, morphologic changes were either subtle or absent. The absence of widespread response is attributed primarily to periodic “flooding” of the diverted channel. During wetter‐than‐average years when excess water is available, minimal flow is diverted and the hydrograph resembles a free‐flowing regime. The release of high flow to the natural channel potentially offsets changes in form incurred during “dry” periods. The stable nature and structure of subalpine channels also contributes to the absence of reduced capacity.
Environmental effects of drainage, drain-blocking and prescribed vegetation burning in UK upland peatlands

Peatlands are important ecosystems for carbon (C) storage, provision of water resources and biodiversity. UK blanket peats represent 10—15% of those found worldwide. While many peatlands continue to be managed through artificial drainage and vegetation burning, it has long been recognized that local habitats and ecological diversity are strongly influenced by these practices. This paper reviews the hydrological, physicochemical and ecological effects of three widespread UK peatland management practices, namely artificial drainage, drain-blocking and rotational heather burning. Drainage and burning of peat often lead to altered runoff regimes, oxidation of organic matter, changes to C, nitrogen (N) and phosphorus (P) cycling, and increased metal and suspended sediment concentrations in streams relative to intact peatlands. Although artificial drainage is now rarely implemented on UK upland peats, a great number of historical drains remain, thus drain-blocking is increasingly being applied to restore many peatlands. In contrast, recent increases in the intensity and extent of rotational heather burning may result in further changes to peatland ecosystems. Relatively little is known about the environmental effects of rotational heather burning compared with drainage and drain-blocking management, and for all three of these management techniques there is scarce information on river ecosystem response. We hypothesize some likely effects of basin-scale drainage, drain-blocking and heather burning on stream ecosystems and illustrate these with a schematic model. Such a holistic consideration of peatland river basins is particularly timely with respect to the implementation of the EU Water Framework Directive.
Inferring surface solar absorption from broadband satellite measurements

Abstract An atmospheric solar radiation model, in conjunction with a variety of surface albedo models, has been employed to address several issues related to inferring the surface solar radiation budget from satellite measurements. With reference to albedo determinations using narrowband instruments such as GOES and METEOSAT, it is suggested that converting these to broadband quantities, either at the surface or at the top of the atmosphere, could be a formidable task for vegetated surfaces. To do this operationally it would seem necessary to subdivide vegetated surface into a large number of categories, incorporate some appropriate means of scene identification, account for probable seasonal variations in surface albedo and surface anisotropy, and then devise a quantitative method for actually performing the conversions. It would be preferable to evaluate broadband quantities from broadband measurements. A further point of this paper, however, is that a commonly used linear conversion between broadband p.
Architecture of the fungal nuclear pore inner ring complex

Building a gate to the nucleus Nuclear pore complexes form a gateway between the cytoplasm and the nucleus (see the Perspective by Ullman and Powers). Stuwe et al. combined structural, biochemical, and functional analyses to elucidate the architecture of a six-protein complex that makes up the inner ring of the fungal nuclear pore. This includes a central trimeric complex homologous to the Nup62 complex found in metazoans that is incorporated into the nuclear pore inner-ring complex. Chug et al. report the structure of the metazoan trimeric Nup62 complex. Neither study supports a model in which the pore can dilate and constrict. Instead they suggest a rigid pore in which flexible domains called FG repeats fill the channel and form a barrier that can be traversed by receptors that carry cargos across. Science, this issue pp. 56 and 106; see also p. 33 A central complex in the nuclear pore forms a rigid channel filled with flexible domains that form a barrier. [Also see Perspective by Ullman and Powers] The nuclear pore complex (NPC) constitutes the sole gateway for bidirectional nucleocytoplasmic transport. We present the reconstitution and interdisciplinary analyses of the ~425-kilodalton inner ring complex (IRC), which forms the central transport channel and diffusion barrier of the NPC, revealing its interaction network and equimolar stoichiometry. The Nsp1•Nup49•Nup57 channel nucleoporin heterotrimer (CNT) attaches to the IRC solely through the adaptor nucleoporin Nic96. The CNT•Nic96 structure reveals that Nic96 functions as an assembly sensor that recognizes the three-dimensional architecture of the CNT, thereby mediating the incorporation of a defined CNT state into the NPC. We propose that the IRC adopts a relatively rigid scaffold that recruits the CNT to primarily form the diffusion barrier of the NPC, rather than enabling channel dilation.
Tiotropium inhibits methacholine-induced extracellular matrix production via β-catenin signaling in human airway smooth muscle cells

Background Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear. Purpose In this study, we attempted to investigate the influence of tiotropium on ECM production by ASMCs and the underlying mechanism. Methods Tiotropium was added 30 minutes before the addition of methacholine to primary cultured human ASMCs. Protein expression was analylized by Western Blot and mRNA abundance was determined by real-time PCR. Results We found that tiotropium reduced collagen I protein expression, and the mRNA abundance of collagen I, fibronectin, and versican. β-catenin signaling was inactivated by inhibiting glycogen synthase kinase 3β (GSK3β) phosphorylation in this process. Tiotropum inhibited the amount of active β-catenin and its transcription activity. Furthermore, overexpression of active β-catenin by adenoviruses carrying the S33Y mutant resisted the suppressive effect of tiotropium on collagen I protein expression. However, silencing β-catenin by specific small interfering RNA enhanced the negative effect of tiotropium. Conclusion These findings suggest that relaxation of ASMCs by tiotropium can prevent ECM production through β-catenin signaling.
Residential proximity to green spaces and breast cancer risk : the multicase-control 1 study in Spain ( MCC-Spain ) 2

32 Background: Breast cancer is the main cause of cancer mortality among women. Green 33 spaces have been recently associated with reduced cancer mortality among women. 34 Mechanisms explaining the beneficial effect of green spaces include increased levels of 35 physical activity and reduced exposure to air pollution, which have been both associated 36 with cancer development. 37 Objectives: To investigate the associations between presence of urban green areas, 38 presence of agricultural areas and surrounding greenness and risk of breast cancer, and 39 to assess whether these associations are mediated by physical activity and/or air 40 pollution levels. 41 Methods: We geocoded the current residence of 1129 breast cancer cases and 1619 42 controls recruited between 2008-13 in ten provinces of Spain, as part of the MCC-Spain 43 study. We assigned different indicators of exposure to green spaces in a buffer of 300 44 m, and in nested buffers of 100 m and 500 m around the residence: presence of urban 45 green areas according to Urban Atlas, presence of agricultural areas according to 46 CORINE Land Cover 2006, and surrounding greenness according to the average of the 47 Normalized Difference Vegetation Index. We used logistic mixed-effects regression 48 models with a random effect for hospital adjusting for potential confounders. We 49 explored the effect of several potential effect modifiers. We assessed mediation effect 50 by physical activity and levels of air pollution. 51 Results: Presence of urban green areas was associated with reduced risk of breast cancer 52 after adjusting for age, socio-economic status at individual and at area level, education, 53 and number of children [OR (95%CI)=0.65 (0.49 – 0.86)]. There was evidence of a 54 linear trend between distance to urban green areas and risk of breast cancer. On the 55 contrary, presence of agricultural areas and surrounding greenness were associated with 56 increased risk of breast cancer [adjusted OR (95%CI)=1.33 (1.07–1.65) and adjusted 57 OR (95%CI)=1.27 (0.92 1.77), respectively]. None of the associations observed were 58 mediated by levels of physical activity or levels or air pollution. 59 Conclusions: The association between green spaces and risk of breast cancer is 60 dependent on land-use. The confirmation of these results in other settings and the study 61 of potential mechanisms for the associations observed are needed to advance the 62 understanding on the potential effects of green spaces on health. 63
Delphi Method Consensus on Priority Global Otolaryngology–Head and Neck Surgery Conditions and Procedures

Objective The objective of this study was to develop an international expert consensus on priority otolaryngology–head and neck surgery conditions and procedures globally for which national health systems should be capable of caring. Study Design The Delphi method was employed via a multiround online survey administered to attending otolaryngologists in an international research collaborative of >180 otolaryngologists in >40 countries. Setting International online survey. Methods In round 1, participants listed the top 15 otolaryngologic conditions and top 15 otolaryngology procedures for their World Bank regions. In round 2, participants ranked round 1 responses in order of global importance on a 5-point Likert scale. In round 3, participants reranked conditions and procedures that did not achieve consensus, defined as 50% of the round 2 Likert responses being ranked as “important” or “very important. ” Descriptive statistics were calculated for each round. Results The survey was distributed to 53 experts globally, with a response rate of 38% (n = 20). Fifty percent (n = 10) of participants were from low- and middle-income countries, with at least 1 participant from each World Bank region. Ten consensus surgical procedures and 10 consensus conditions were identified. Conclusion This study identified a list of priority otolaryngology–head and neck surgery conditions and surgical procedures for which all national health systems around the world should be capable of managing. Acute and infectious conditions with preventative and emergent procedures were highlighted. These findings can direct future research and guide international collaborations.