Unraveling the roles of IFIT3 gene and immune-metabolic pathways in psoriasis: a bioinformatics exploration for diagnostic markers and therapeutic targets.

Background: The functions and related signal pathways of the IFIT3 gene in the skin lesions of patients with psoriasis were explored through bioinformatics methods to determine the potential specific molecular markers of psoriasis. Methods: The "limma" R package was used to analyze three datasets from the Gene Expression Omnibus database (GSE13355, GSE30999 and GSE106992), and the differential genes were screened. The STRING database was used for gene ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, and protein-protein interaction network integration. Then, the IFIT3 subnetwork was extracted and analyzed by gene set enrichment analysis (GSEA) using the Metascape database to verify the effectiveness of gene differentiation and disease tissue identification. Results: In this study, 426 differential genes were obtained, of which 322 were significantly upregulated and 104 were significantly downregulated. GO enrichment analysis showed that the differential genes were mainly involved in immunity and metabolism; the KEGG pathway enrichment analysis mainly included the chemokine signal pathway, PPAR signal pathway, and IL-17 signal pathway, among others. Based on the IFIT3 subnetwork analysis, it was found that IFIT3 was mainly involved in the biological processes of viruses, bacteria, and other microorganisms. The pathways obtained by GSEA were mainly related to immunity, metabolism, and antiviral activities. IFIT3 was highly expressed in psoriatic lesions and may thus be helpful in the diagnosis of psoriasis. Conclusion: The differential genes, biological processes, and signal pathways of psoriasis, especially information related to and diagnostic efficiency of the IFIT3 gene, were obtained by bioinformatics analysis. These results are expected to provide the theoretical basis and new directions for exploring the pathogenesis of psoriasis, in addition to helping with finding diagnostic markers and developing drug treatment targets.

Model-based orbital-scale precipitation δ18O variations and distinct mechanisms in Asian monsoon and arid regions.

The past Asian precipitation δ18O (δ18Op) records from stalagmites and other deposits have shown significant orbital-scale variations, but their climatic implications and regional differences are still not fully understood. This study, as the first attempt of a 300-kyr transient stable isotope-enabled simulation, investigated the characteristics and mechanisms of the orbital-scale δ18Op variations in three representative regions of Asia: arid Central Asia (CA), monsoonal South Asia (SA) and monsoonal East Asia (EA). The modelling results showed that the variations in the CA, SA and EA annual δ18Op exhibited significant but asynchronous 23-kyr precession cycles. Further analyses revealed that although the precession-induced insolation variation was the ultimate cause of the δ18Op variation in all three regions, the dominant mechanisms and the involved physical processes were distinct among them. For the CA region, the rainy-season (November-March) temperature effect and water vapour transport by the westerly circulation were identified as the key precession-scale processes linking the October-February boreal mid-latitude insolation to the rainy-season or annual δ18Op. In the SA region, the rainy-season (June-September) precipitation amount effect and upstream depletion of the monsoonal water vapour δ18O served as the main mechanisms linking the rainy-season or annual δ18Op to the April-July insolation variation at the precession scale. For the EA region, however, the precession-scale annual δ18Op was mainly controlled by the late-monsoon (August-September) and pre-monsoon (April-May) water vapour transport patterns, which were driven by the July-August insolation and the global ice volume, respectively. These results suggest that the climatic implications of the orbital-scale Asia δ18Op variations are sensitive to their geographic locations as determined by the combined effects of insolation and regional circulation patterns associated with the respective rainy seasons. This study provides new insights into understanding the regional differences and formation mechanisms of the Asian orbital-scale δ18Op variations.

Loureirin A Exerts Antikeloid Activity by Antagonizing the TGF-ß1/Smad Signalling Pathway.

It has been recently shown that loureirin A (LA), a major active component of resina draconis, might be effective in the prevention and treatment of liver fibrosis. We examined whether LA could inhibit the formation of keloids. To investigate the pharmacological effects of loureirin A on keloid formation and the underlying mechanisms. CellTiter-Blue viability assays were used to examine the proliferation of keloid fibroblasts (KFs) that were treated with LA. Fibroblast migration was evaluated using a cell migration assay. Immunofluorescence staining was used to measure the expression of α-SMA in KFs. RT-qPCR was used to evaluate the mRNA expression of Col-I, Col-III, α-SMA, Bax, and Caspase-3, while Western blotting was used to evaluate the protein expression of Col-I, Col-III, α-SMA, Bax, Caspase-3, p-Smad2, and p-Smad3. LA inhibited the proliferation of KFs and suppressed the migration and TGF-ß1-induced myofibroblast differentiation of KFs. In addition, LA downregulated the mRNA and protein levels of Col-I, Col-III, and α-SMA while promoting the mRNA and protein levels of Bax and Caspase-3. Moreover, LA downregulated the protein levels of p-Smad2 and p-Smad3 in cultured TGF-ß1-treated KFs ex vivo. These results show that LA has an antikeloid effect on KFs by suppressing the TGF-ß1/Smad signalling pathway. Our findings suggest that LA may be a potential candidate drug for the prevention and treatment of keloids.

Finite-time controller design with adaptive fixed-time anti-saturation compensator for hypersonic vehicle.

An adaptive anti-saturation robust finite-time control algorithm (AARFTC) is designed for flexible air-breathing hypersonic vehicle (FAHV) under actuator saturations. Firstly, an adaptive fixed-time anti-saturation compensator (AFAC) is presented to drive system to faster leave the saturated region Compared to traditional anti-saturation compensators, the auxiliary variable of AFAC is able to realize faster and more accurate convergence when saturation disappears, which avoids the influence on convergent characteristics of tracking error. In addition, the novel adaptive law in AFAC can further shorten the duration of saturation and improve the convergent speed of tracking error via adjusting gain in AFAC according to saturation of actuator. Then, dynamic inversion control is combined with AFAC to establish anti-saturation controller for velocity subsystem. Secondly, differentiator-based backstepping control is combined with AFAC for height subsystem. Two recursive fixed settling time differentiators are utilized to approximate derivatives of virtual control signals exactly in fixed time, which avoids the complex computational burden residing in traditional backstepping control and improves convergent accuracy compared to command filtered backstepping control. Meanwhile, AFAC is utilized to suppress the influence of elevator saturation. Ultimately, multiple sets of simulations on FAHV subject to external disturbances, parametric uncertainties and actuator saturations are carried out to show the superiorities of AFAC and AARFTC.

African climate response to orbital and glacial forcing in 140,000-y simulation with implications for early modern human environments.

A climate/vegetation model simulates episodic wetter and drier periods at the 21,000-y precession period in eastern North Africa, the Arabian Peninsula, and the Levant over the past 140,000 y. Large orbitally forced wet/dry extremes occur during interglacial time, ∼130 to 80 ka, and conditions between these two extremes prevail during glacial time, ∼70 to 15 ka. Orbital precession causes high seasonality in Northern Hemisphere (NH) insolation at ∼125, 105, and 83 ka, with stronger and northward extended summer monsoon rains in North Africa and the Arabian Peninsula and increased winter rains in the Mediterranean Basin. The combined effects of these two seasonally distinct rainfall regimes increase vegetation and narrow the width of the Saharan-Arabian desert and semidesert zones. During the opposite phase of the precession cycle (∼115, 95, and 73 ka), NH seasonality is low, and decreased summer insolation and increased winter insolation cause monsoon and storm track rains to decrease and the width of the desert zone to increase. During glacial time (∼70 to 15 ka), forcing from large ice sheets and lowered greenhouse gas concentrations combine to increase winter Mediterranean storm track precipitation; the southward retreat of the northern limit of summer monsoon rains is relatively small, thereby limiting the expansion of deserts. The lowered greenhouse gas concentrations cause the near-equatorial zone to cool and reduce convection, causing drier climate with reduced forest cover. At most locations and times, the simulations agree with environmental observations. These changing regional patterns of climate/vegetation could have influenced the dispersal of early humans through expansions and contractions of well-watered corridors.

Resolving seasonal rainfall changes in the Middle East during the last interglacial period.

Paleorainfall proxy records from the Middle East have revealed remarkable patterns of variability since the penultimate glacial period (140 ka), but the seasonality of this signal has been unresolvable. Here, seasonal-resolution oxygen isotope data from Soreq Cave speleothems suggest that summer monsoon rainfall periodically reaches as far north as Israel-well removed from the modern monsoon-at times (∼125, 105 ka) that overlap with evidence for some of the earliest modern human migrations out of Africa. These seasonal proxy data are corroborated by seasonal-resolution model output of the amount and oxygen-isotope ratio of rainfall from an isotope-enabled climate model. In contrast to the modern regional climate where rainfall is delivered predominantly in winter months along westerly storm tracks, the model suggests that during extreme peaks of summer insolation-as occurs during the last interglacial (e.g., 125, 105 ka)-regional rainfall increases due to both wetter winters and the incursion of summer monsoons. This interpretation brings clarity to regional paleoproxy records and provides important environmental context along one potential pathway of early modern human migration.

[Numerical simulations of spatial and temporal characteristics of airborne dust over Asia during springs of 2000 to 2002].

Spatial and temporal characteristics of airborne dust over Asia during springs of 2000, 2001 and 2002 were simulated with a mineral dust entrainment and deposition model (DEAD) embedded in a global model of atmospheric transport and chemistry (MATCH) using the real-time meteorological data as forcing fields. The results show a good agreement of the pattern of model-simulated atmospheric dust concentration with the distribution of surface-observed spring dust storm frequency and a significant correlation between the simulated dust aerosol optical depth (DAOD) and satellite-observed aerosol index (AI). These results validate applicability of the integrated model in simulating dust entrainment, transportation and deposition and describing spatial and temporal characteristics of dust loading over the Asian continent. In addition, an attempt was made to explore possible paths of dust transportation by use of correlation analyses between the simulated dust emission flux (DEF) and DAOD.