The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death ...in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.
•Cytokine release syndrome (CRS) contributes to life-threatening multiple organ dysfunction in coronavirus disease 2019 (COVID-19) and represents a potential therapeutic target.•Mechanistic understanding of CRS permits the design of novel immunotherapies.•Targeting key molecules within the inflammatory cytokine network, such as interleukin-6 (IL-6), is a novel strategy for COVID-19-induced CRS and warrants further investigation.
Summary
Type 1 diabetes (T1D) is an autoimmune disease, which is characterized by the destruction of islet β cells in the pancreas triggered by genetic and environmental factors. In past decades, ...extensive familial and genome‐wide association studies have revealed more than 50 risk loci in the genome. However, genetic susceptibility cannot explain the increased incidence of T1D worldwide, which is very likely attributed by the growing impact of environmental factors, especially gut microbiome. Recently, the role of gut microbiome in the pathogenesis of T1D has been uncovered by the increasing evidence from both human subjects and animal models, strongly indicating that gut microbiome might be a pivotal hub of T1D‐triggering factors, especially environmental factors. In this review, we summarize the current aetiological and mechanism studies of gut microbiome in T1D. A better understanding of the role of gut microbiome in T1D may provide us with powerful prognostic and therapeutic tools in the near future.
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic ...fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells. PDX1 also binds to the regulatory elements and increases insulin gene transcription. Likewise, MAFA binds to the enhancer/promoter region of the insulin gene and drives insulin expression in response to glucose. In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. Here, we review biological properties of PDX1, NEUROG3, and MAFA, and their applications and limitations for beta cell regenerative approaches. The primary source literature for this review was acquired using a PubMed search for articles published between 1990 and 2017. Search terms include diabetes, insulin, trans-differentiation, stem cells, and regenerative medicine.
Summary
A wealth of epidemiological studies concerning the distribution of type 1 diabetes (T1D) around the world have pointed to the appreciable variation in the incidence of T1D among disparate age ...groups, ethnicities, and geographical locations. On the whole, the incidence of childhood T1D has been on the rise, and a plausible inverse relationship between the initial incidence rate and the following annual increase in incidence has been raised. Countries that used to exhibit lower incidences tend to have steep annual increase whereas those with already‐established high incidences are more likely to show a modest increase or even stabilization in T1D incidence. Environmental agents considered responsible for the current evolving pattern of T1D incidence will be detailed, mainly including the increasing prevalence of childhood obesity, viral infections in a chronic manner, maternal‐child interaction such as breastfeeding, and latitude‐ultraviolet B‐vitamin D pathway. Certain rationale has been put forward in an attempt to explain the potential association between environmental agents and development of T1D. For instance, accelerator hypothesis regards insulin resistance as the promoter of earlier disease onset in obese children whereas the negative correlation of microbial infections in background populations with incidence of T1D represents the basic component of the hygiene hypothesis. Further investigations are still warranted to verify these theories across multiple ethnic groups and to identify additional contributors to the variation in T1D incidence.
Lanthanide-doped glasses and crystals are attractive for laser applications because the metastable energy levels of the trivalent lanthanide ions facilitate the establishment of population inversion ...and amplified stimulated emission at relatively low pump power. At the nanometre scale, lanthanide-doped upconversion nanoparticles (UCNPs) can now be made with precisely controlled phase, dimension and doping level. When excited in the near-infrared, these UCNPs emit stable, bright visible luminescence at a variety of selectable wavelengths, with single-nanoparticle sensitivity, which makes them suitable for advanced luminescence microscopy applications. Here we show that UCNPs doped with high concentrations of thulium ions (Tm
), excited at a wavelength of 980 nanometres, can readily establish a population inversion on their intermediate metastable
H
level: the reduced inter-emitter distance at high Tm
doping concentration leads to intense cross-relaxation, inducing a photon-avalanche-like effect that rapidly populates the metastable
H
level, resulting in population inversion relative to the
H
ground level within a single nanoparticle. As a result, illumination by a laser at 808 nanometres, matching the upconversion band of the
H
→
H
transition, can trigger amplified stimulated emission to discharge the
H
intermediate level, so that the upconversion pathway to generate blue luminescence can be optically inhibited. We harness these properties to realize low-power super-resolution stimulated emission depletion (STED) microscopy and achieve nanometre-scale optical resolution (nanoscopy), imaging single UCNPs; the resolution is 28 nanometres, that is, 1/36th of the wavelength. These engineered nanocrystals offer saturation intensity two orders of magnitude lower than those of fluorescent probes currently employed in stimulated emission depletion microscopy, suggesting a new way of alleviating the square-root law that typically limits the resolution that can be practically achieved by such techniques.
Our understanding of the assembly history of Asia depends critically on the tectonic relationships between its major cratons, including Siberia, North China, South China, and Tarim. The intervening ...microcontinents between these cratons can provide insight into the paleogeographic and paleotectonic relationships of the cratons, but there is currently a general lack of knowledge regarding the basement geology of these microcontinents. Here we present results from systematic geologic mapping, U-Pb zircon dating, whole-rock geochemical analysis, and synthesis of existing data to establish the Proterozoic to early Paleozoic evolution of the central Qilian basement to the south of the North China craton in northwest China. Our results indicate that the region underwent three major periods of magmatic activity at 960-880, 877-710, and 550-375 Ma. Our geochemical analysis suggests that the ca. 900 Ma plutons were generated during arc magmatism and/or syncollisional crustal melting, whereas the ca. 820 Ma plutons are A-type granitoids, which are typically associated with extensional tectonism. Igneous zircons from a high- and ultrahigh-pressure eclogite in the north-central Qilian Shan have a U-Pb age of ca. 916 Ma, whereas dating of the recrystallized rims suggests that eclogite facies metamorphism occurred at ca. 485 Ma. Our detrital zircon geochronology also indicates that a widespread metasedimentary unit in the region was deposited between ca. 1200 and ca. 960 Ma, prior to the onset of a rift-drift event at ca. 750 Ma. Based on regional geologic constraints and the magmatic history, we propose the following tectonic history: (1) the paleo-Qilian Ocean bound the combined North Tarim-North China craton to the south (present-day coordinates) in the Mesoproterozoic; (2) the paleo-Qilian Ocean closed between 900 and 820 Ma following the collision of North Tarim-North China craton and the South Tarim-Qaidam-Kunlun continent; (3) the younger Qilian Ocean opened at ca. 775 Ma along the previous suture trace of the paleo-Qilian Ocean as a marginal sea within southern Laurasia; and (4) this ocean closed by ca. 445-440 Ma as a result of collision between the Tarim-North China cratons and the Qaidam-Kunlun continent along a south-dipping subduction system.
AbstractObjectiveTo estimate the incidence of type 1 diabetes in all age groups in China during 2010-13.DesignPopulation based, registry study using data from multiple independent ...sources.SettingNational registration system in all 505 hospitals providing diabetes care, and communities of patients with diabetes in 13 areas across China, covering more than 133 million person years at risk, approximately 10% of the whole population.Participants5018 people of all ages with newly diagnosed type 1 diabetes and resident in the study areas from 1 January 2010 to 31 December 2013.Main outcome measuresIncidence of type 1 diabetes per 100 000 person years by age, sex, and study area. Type 1 diabetes was doctor diagnosed and further validated by onsite follow-up. Completeness of case ascertainment was assessed using the capture mark recapture method.Results5018 cases of newly diagnosed type 1 diabetes were ascertained: 1239 participants were aged <15 years, 1799 were aged 15-29 years, and 1980 were aged ≥30 years. The proportion of new onset cases in participants aged ≥20 years was 65.3%. The estimated incidence of type 1 diabetes per 100 000 persons years for all ages in China was 1.01 (95% confidence interval 0.18 to 1.84). Incidence per 100 000 persons years by age group was 1.93 (0.83 to 3.03) for 0-14 years, 1.28 (0.45 to 2.11) for 15-29 years, and 0.69 (0.00 to 1.51) for ≥30 years, with a peak in age group 10-14 years. The incidence in under 15s was positively correlated with latitude (r=0.88, P<0.001), although this association was not observed in age groups 15-29 years or ≥30 years.ConclusionMost cases of new onset type 1 diabetes in China occurred among adults. The incidence of type 1 diabetes in Chinese children was among the lowest reported in the study.
The present-day Tibetan plateau, which is the largest highland on Earth, formed primarily due to the India-Asia collision since 50-60 Ma. The development of the plateau has been associated with the ...Cenozoic development of two large intra-plateau sedimentary basins in north-central Tibet: the Qaidam and Hoh Xil basins to the north and south of the Eastern Kunlun Range, respectively. We conducted an integrated study of these two basins and the Eastern Kunlun Range that separates them to understand the timing and mechanisms of their development in order to decipher the growth and uplift history of the plateau. Crustal shortening in the Fenghuoshan-Nangqian and Qilian Shan-Nan Shan thrust belts initiated no later than the early Eocene, which formed the northern and southern boundaries of the combined Hoh Xil and Qaidam basins in central Tibet. The distinct two-stage development of the Hoh Xil basin suggests emergence of a topographic barrier between the Hoh Xil basin in the south and Qaidam basin in the north in the early Neogene, which is supported by the existing and new apatite fission-track data from the Eastern Kunlun Range that suggest rapid cooling after ca. 20 Ma. Previous and newly collected geochronological, petrological, and thermochronological data are best interpreted in the context of the Paleogene Paleo-Qaidam hypothesis, which requires Hoh Xil and Qaidam basins to have been parts of a single integrated basin during the early stage of the Cenozoic Tibetan plateau development.
Diabetes poses heavy social and economic burdens worldwide. Diabetes management apps show great potential for diabetes self-management. However, the adoption of diabetes management apps by diabetes ...patients is poor. The factors influencing patients' intention to use these apps are unclear. Understanding the patients' behavioral intention is necessary to support the development and promotion of diabetes app use.
This study aimed to identify the determinants of patients' intention to use diabetes management apps based on an integrated theoretical model.
The hypotheses of our research model were developed based on an extended Unified Theory of Acceptance and Use of Technology (UTAUT). From April 20 to May 20, 2019, adult patients with diabetes across China, who were familiar with diabetes management apps, were surveyed using the Web-based survey tool Sojump. Structural equation modeling was used to analyze the data.
A total of 746 participants who met the inclusion criteria completed the survey. The fitness indices suggested that the collected data fit well with the research model. The model explained 62.6% of the variance in performance expectancy and 57.1% of the variance in behavioral intention. Performance expectancy and social influence had the strongest total effects on behavioral intention (β=0.482; P=.001). Performance expectancy (β=0.482; P=.001), social influence (β=0.223; P=.003), facilitating conditions (β=0.17; P=.006), perceived disease threat (β=0.073; P=.005), and perceived privacy risk (β=-0.073; P=.012) had direct effects on behavioral intention. Additionally, social influence, effort expectancy, and facilitating conditions had indirect effects on behavioral intention that were mediated by performance expectancy. Social influence had the highest indirect effects among the three constructs (β=0.259; P=.001).
Performance expectancy and social influence are the most important determinants of the intention to use diabetes management apps. Health care technology companies should improve the usefulness of apps and carry out research to provide clinical evidence for the apps' effectiveness, which will benefit the promotion of these apps. Facilitating conditions and perceived privacy risk also have an impact on behavioral intention. Therefore, it is necessary to improve facilitating conditions and provide solid privacy protection. Our study supports the use of UTAUT in explaining patients' intention to use diabetes management apps. Context-related determinants should also be taken into consideration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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