Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury

BackgroundMicrovascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and macrovascular complications, referring to atherosclerosis (AS), are the main complications of diabetes. Blindness or fatal microvascular diseases are considered to be identified earlier than fatal macrovascular complications. Exploring the intrinsic relationship between microvascular and macrovascular complications and the hub of pathogenesis is of vital importance for prolonging the life span of patients with diabetes and improving the quality of life.Materials and methodsThe expression profiles of GSE28829, GSE30529, GSE146615 and GSE134998 were downloaded from the Gene Expression Omnibus database, which contained 29 atherosclerotic plaque samples, including 16 AS samples and 13 normal controls; 22 renal glomeruli and tubules samples from diabetes nephropathy including 12 DN samples and 10 normal controls; 73 lymphoblastoid cell line samples, including 52 DR samples and 21 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques including GSEA analysis, GO-KEGG functional clustering by R (version 4.0.5), PPI analysis by Cytoscape (version 3.8.2) and String database, miRNA analysis by Diana database, and hub genes analysis by Metascape database. The drug sensitivity of characteristic DEGs was analyzed.ResultA total of 3709, 4185 and 8086 DEGs were recognized in AS, DN, DR, respectively, with 1820, 1666, 888 upregulated and 1889, 2519, 7198 downregulated. GO and KEGG pathway analyses of DEGs and GSEA analysis of common differential genes demonstrated that these significant sites focused primarily on inflammation-oxidative stress and immune regulation pathways. PPI networks show the connection and regulation on top-250 significant sites of AS, DN, DR. MiRNA analysis explored the non-coding RNA upstream regulation network and significant pathway in AS, DN, DR. The joint analysis of multiple diseases shows the common influenced pathways of AS, DN, DR and explored the interaction between top-1000 DEGs at the same time.ConclusionIn the microvascular and macrovascular complications of diabetes, immune-mediated inflammatory response, chronic inflammation caused by endothelial cell activation and oxidative stress are the three links linking atherosclerosis, diabetes retinopathy and diabetes nephropathy together. Our study has clarified the intrinsic relationship and common tissue damage mechanism of microcirculation and circulatory system complications in diabetes, and explored the mechanism center of these two vascular complications. It has far-reaching clinical and social value for reducing the incidence of fatal events and early controlling the progress of disabling and fatal circulatory complications in diabetes

Interplay between moment-dependent and field-driven unidirectional magnetoresistance in CoFeB/InSb/CdTe heterostructures

Magnetoresistance effects are crucial for understanding the charge/spin transport as well as propelling the advancement of spintronic applications. Here we report the coexistence of magnetic moment-dependent (MD) and magnetic field-driven (FD) unidirectional magnetoresistance (UMR) effects in CoFeB/InSb/CdTe heterostructures. The strong spin-orbital coupling of InSb and the matched impedance at the CoFeB/InSb interface warrant a distinct MD-UMR effect at room temperature, while the interaction between the in-plane magnetic field and the Rashba effect at the InSb/CdTe interface induces the marked FD-UMR signal that dominates the high-field region. Moreover, owning to the different spin transport mechanisms, these two types of nonreciprocal charge transport show opposite polarities with respect to the magnetic field direction, which further enable an effective phase modulation of the angular-dependent magnetoresistance. Besides, the demonstrations of both the tunable UMR response and two-terminal spin-orbit torque-driven magnetization switching validate our CoFeB/InSb/CdTe system as a suitable integrated building block for multifunctional spintronic device design

The genome and gene editing system of sea barleygrass provide a novel platform for cereal domestication and stress tolerance studies

The tribe Triticeae provides important staple cereal crops and contains elite wild species with wide genetic diversity and high tolerance to abiotic stresses. Sea barleygrass (Hordeum marinum Huds.), a wild Triticeae species, thrives in saline marshlands and is well known for its high tolerance to salinity and waterlogging. Here, a 3.82-Gb high-quality reference genome of sea barleygrass is assembled de novo, with 3.69 Gb (96.8%) of its sequences anchored onto seven chromosomes. In total, 41 045 high-confidence (HC) genes are annotated by homology, de novo prediction, and transcriptome analysis. Phylogenetics, non-synonymous/synonymous mutation ratios (Ka/Ks), and transcriptomic and functional analyses provide genetic evidence for the divergence in morphology and salt tolerance among sea barleygrass, barley, and wheat. The large variation in post-domestication genes (e.g. IPA1 and MOC1) may cause interspecies differences in plant morphology. The extremely high salt tolerance of sea barleygrass is mainly attributed to low Na+ uptake and root-to-shoot translocation, which are mainly controlled by SOS1, HKT, and NHX transporters. Agrobacterium-mediated transformation and CRISPR/Cas9-mediated gene editing systems were developed for sea barleygrass to promote its utilization for exploration and functional studies of hub genes and for the genetic improvement of cereal crops

Suppression of renal cell carcinoma growth in vivo by forced expression of vascular endothelial growth inhibitor

Vascular endothelial growth inhibitor (VEGI) has been associated with tumor-related vasculature in certain malignancies. However, its implication in renal cell carcinoma (RCC), an angiogenesis-dependent tumor, remains unknown. In the present study, we investigated the role played by VEGI in RCC. The expression of VEGI was examined in human renal tissue and RCC cell lines using immunohistochemical staining and RT-PCR, respectively. The biological impact of modifying the expression of VEGI in RCC cells was evaluated using in vitro and in vivo models. We show that VEGI mRNA is expressed in a wide variety of human RCC cell lines, all of normal renal and most of RCC tissue specimens. VEGI protein expression was observed in normal renal tubular epithelial cells, but was decreased or absent in RCC specimens, particularly in tumors with high grade. Moreover, forced expression of VEGI led to an inhibition of vascular endothelial tube formation, decrease in the motility and adhesion of RCC cells in vitro. Interestingly, forced expression of VEGI had no bearing on growth, apoptosis and invasive capacity of RCC cells. However, tumor growth was reduced in xenograft models. Immunohistochemical staining showed that microvessel density decreased in VEGI forced expression xenograft tumor samples. Taken together, our findings showed that the expression of VEGI is decreased in RCC, particularly in tumors with higher grade. Together with its inhibitory effect on cellular motility, adhesion, vascular endothelial tube formation and tumor growth in vivo, this suggests that VEGI functions mainly through inhibition of angiogenesis and is a negative regulator of aggressiveness during the development and progression of RCC

Minute-Cadence Observations of the LAMOST Fields with the TMTS V. Machine Learning Classification of TMTS Catalogues of Periodic Variable Stars

Periodic variables are always of great scientific interest in astrophysics. Thanks to the rapid advancement of modern large-scale time-domain surveys, the number of reported variable stars has experienced substantial growth for several decades, which significantly deepened our comprehension of stellar structure and binary evolution. The Tsinghua University-Ma Huateng Telescopes for Survey (TMTS) has started to monitor the LAMOST sky areas since 2020, with a cadence of 1 minute. During the period from 2020 to 2022, this survey has resulted in densely sampled light curves for ~ 30,000 variables of the maximum powers in the Lomb-Scargle periodogram above the 5sigma threshold. In this paper, we classified 11,638 variable stars into 6 main types using XGBoost and Random Forest classifiers with accuracies of 98.83% and 98.73%, respectively. Among them, 5301 (45.55%) variables are newly discovered, primarily consisting of Delta Scuti stars, demonstrating the capability of TMTS in searching for short-period variables. We cross-matched the catalogue with Gaia's second Data Release (DR2) and LAMOST's seventh Data Release (DR7) to obtain important physical parameters of the variables. We identified 5504 Delta Scuti stars (including 4876 typical Delta Scuti stars and 628 high-amplitude Delta Scuti stars), 5899 eclipsing binaries (including EA-, EB- and EW-type) and 226 candidates of RS Canum Venaticorum. Leveraging the metal abundance data provided by LAMOST and the Galactic latitude, we discovered 8 candidates of SX Phe stars within the class of "Delta Scuti stars". Moreover, with the help of Gaia color-magnitude diagram, we identified 9 ZZ ceti stars.Comment: 20 pages, 14 figures, accepted to MNRA

Minute-cadence Observations of the LAMOST Fields with the TMTS: III. Statistic Study of the Flare Stars from the First Two Years

Tsinghua University-Ma Huateng Telescopes for Survey (TMTS) aims to detect fast-evolving transients in the Universe, which has led to the discovery of thousands of short-period variables and eclipsing binaries since 2020. In this paper, we present the observed properties of 125 flare stars identified by the TMTS within the first two years, with an attempt to constrain their eruption physics. As expected, most of these flares were recorded in late-type red stars with $G_{\rm BP}-G_{\rm RP}$ > 2.0 mag, however, the flares associated with bluer stars tend to be on average more energetic and have broader profiles. The peak flux (F_peak) of the flare is found to depend strongly on the equivalent duration (ED) of the energy release, i.e., $F_{{\rm peak}} \propto {\rm ED}^{0.72\pm0.04}$, which is consistent with results derived from the Kepler and Evryscope samples. This relation is likely related to the magnetic loop emission, while -- for the more popular non-thermal electron heating model -- a specific time evolution may be required to generate this relation. We notice that flares produced by hotter stars have a flatter $F_{{\rm peak}} \propto {\rm ED}$ relation compared to that from cooler stars. This is related to the statistical discrepancy in light-curve shape of flare events with different colors. In spectra from LAMOST, we find that flare stars have apparently stronger H alpha emission than inactive stars, especially at the low temperature end, suggesting that chromospheric activity plays an important role in producing flares. On the other hand, the subclass having frequent flares are found to show H alpha emission of similar strength in their spectra to that recorded with only a single flare but similar effective temperature, implying that the chromospheric activity may not be the only trigger for eruptions.Comment: 17 pages, 15 figures, 2 tables, refereed version. For associated data files, see https://cdsarc.cds.unistra.fr/viz-bin/cat/J/MNRAS/523/219

An 18.9-minute Blue Large-Amplitude Pulsator Crossing the 'Hertzsprung Gap' of Hot Subdwarfs

Blue large-amplitude pulsators (BLAPs) represent a new and rare class of hot pulsating stars with unusually large amplitudes and short periods. Up to now, only 24 confirmed BLAPs have been identified from more than one billion monitored stars, including a group with pulsation period longer than $\sim 20$ min (classical BLAPs, hereafter) and the other group with pulsation period below $\sim 8$ min. The evolutionary path that could give rise to such kinds of stellar configurations is unclear. Here we report on a comprehensive study of the peculiar BLAP discovered by the Tsinghua University - Ma Huateng Telescopes for Survey (TMTS), TMTS J035143.63+584504.2 (TMTS-BLAP-1). This new BLAP has an 18.9 min pulsation period and is similar to the BLAPs with a low surface gravity and an extended helium-enriched envelope, suggesting that it is a low-gravity BLAP at the shortest-period end. In particular, the long-term monitoring data reveal that this pulsating star has an unusually large rate of period change, P_dot/P=2.2e-6/yr. Such a significant and positive value challenges its origins from both helium-core pre-white-dwarfs and core helium-burning subdwarfs, but is consistent with that derived from shell helium-burning subdwarfs. The particular pulsation period and unusual rate of period change indicate that TMTS-BLAP-1 is at a short-lived (~10^6 yr) phase of shell-helium ignition before the stable shell-helium burning; in other words, TMTS-BLAP-1 is going through a "Hertzsprung gap" of hot subdwarfs.Comment: 26 pages, 12 figures, 4 tables, published on Nature Astronomy, URL: https://www.nature.com/articles/s41550-022-01783-

Impacts on quality-induced water scarcity: drivers of nitrogen-related water pollution transfer under globalization from 1995 to 2009

Globalization enables the transfer of impacts on water availability. We argue that the threat should be evaluated not only by decrease of quantity, but more importantly by the degradation of water quality in exporting countries. Grouping the world into fourteen regions, this paper establishes a multi-region input-output framework to calculate the nitrogen-related grey water footprint and a water quality-induced scarcity index caused by pollution, for the period of 1995 to 2009. It is discovered that grey water embodied in international trade has been growing faster than total grey water footprint. China, the USA and India were the three top grey water exporters which accounted for more than half the total traded grey water. Dilemma rose when China and India were facing highest grey water scarcity. The EU and the USA were biggest grey water importers that alleviated their water stress by outsourcing water pollution. A structural decomposition analysis is conducted to study the drivers to the evolution of virtual flows of grey water under globalization during the period of 1995 to 2009. The results show that despite the technical progress that offset the growth of traded grey water, structural effects under globalization including both evolution in the globalized economic system and consumption structure, together with consumption volume made a positive contribution. It is found that the structural effect intensified the pollution-induced water scarcity of exporters as it generally increased all nations’ imported grey water while resulting in increases in only a few nations’ exported grey water, such as Brazil, China and Indonesia. At last, drawing from the ‘cap-and-trade’ and ‘boarder-tax-adjustment’ schemes, we propose policy recommendations that ensure water security and achieve environmentally sustainable trade from both the sides of production and consumption

reasoning about channel passing in choreography

IEEE Computer Society; IFIP; Nanjing UniversityWeb services choreography describes global models of service interactions among a set of participants. For an interaction to be executed, the participants must know the required channel(s) used in the interaction, otherwise the execution will get stuck.

Reasoning about Channel Passing in Choreography ⋆

Abstract Web services choreography describes global models of service interactions among a set of participants. For an interaction to be executed, the participants taken part in it must know the required channel(s) used in the interaction, otherwise the execution will get stuck. Because of dynamic composition, the initial channel set on each participant is often insufficient to meet the requirements. It is the responsibility of the participants to pass required channels owned (known) by one to some others. Since a choreography may involve many participants and complex channel constraints, it is hard for designers to specify channel passing in a choreography exactly as required. In this paper, we address the problem of checking whether a choreography lacks channels or has redundant channels, and how to automatically generate channel passing based on interaction flows of the choreography in the case of channel absence. Concretely, we propose a small language Chorc named for an channel interaction sub-language for modeling the channel passing aspect of choreography. Based on the formal operational semantics of Chorc, the algorithms for static checking choreography and generating channel passing are studied as well. Moreover, a purchase order choreography example is presented to show how to formalize and analyze a choreography with channel passing in Chorc