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Circular RNAs (circRNA) and N6-methyladenosine (m6A) modification are extensively involved in the progression of diverse tumors, including hepatocellular carcinoma (HCC). However, the cross-talk between circRNAs and m6A remains elusive in the pathogenesis of HCC. Here we investigated m6A-mediated regulation of circRNAs in HCC. m6A-related circRNAs were identified by integrating information from two published studies, revealing circular cleavage and polyadenylation specific factor 6 (circCPSF6) as a novel m6A-modified circRNA. circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated circCPSF6 expression served as an independent prognostic factor for worse survival of patients with HCC. Loss-of-function assays demonstrated that circCPSF6 maintained cell proliferation and tumorigenicity and reinforced cell motility and tumor metastasis. circCPSF6 triggered expression of YAP1, further activating its downstream cascade. Mechanistically, circCPSF6 competitively bound PCBP2, blunting its binding to YAP1 mRNA, thereby sustaining the stability of YAP1. Functionally, removal of YAP1 reversed the effects of circCPSF6 in vitro and in vivo. Aberrant activation of the circCPSF6-YAP1 axis promoted HCC malignancy. These findings offer novel insights into the regulation of circRNAs by m6A modifications and the role of this epigenetic reprogramming in HCC.Significance:This study advances the understanding of the interplay between m6A methylation and circRNAs in hepatocellular carcinoma, highlighting the potential of circCPSF6 as a therapeutic target.

Seasonal changes in wind regime have driven the formation and emergence of reversing dunes and crest reversal in the inland arid and coastal areas of Asia, but due to the strong prevailing winds, the reversing dunes or reversing crest can be flipped. Therefore, the transient reversing dunes or crest reversal will be ignored and unobserved. To investigate dune morphology and sedimentology concerning seasonal alternation of the wind regime, we reconstructed dune topographies using aerial drone photos and analyzed the grain-size parameters and internal sedimentary structures of dunes. Morphological results show that wind-blown sands from the lee side are transported and deposited on the upper stoss side because of the reversing winds. Then, the dune crestal area is flattened, surface sand compositions were reorganized from fining to coarsening at the dune crest. Combining these field surveys with numerical simulation results, we found that the internal sedimentary structures are composed of high-angle cross-strata and low-angle bounding surfaces. The dip angles of the bounding surfaces gradually decrease from the bottom to the top because of the reversing wind erosion on the lee side. The increase in sand flux on the lee side plays a critical role in shaping the dip angle of the bounding surfaces due to the speed-up effect.

Irisin is a newly discovered exercise-induced cytokine, produced by the proteolytic hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Irisin is widely distributed in the human body and is involved in the browning of white adipose tissue, improving insulin resistance, improving cognitive function, and regulating bone metabolism. Recent studies have shown that irisin concentration is elevated in a variety of tumor tissues as compared with that in normal tissues. However, irisin has different effects on the proliferation and apoptosis of tumor cells in breast cancer, lung cancer, and liver cancer through various mechanisms. Irisin plays an important role in the occurrence, development, and metastasis of different tumors, suggesting that irisin can be used as a potential target for tumor diagnosis and treatment. Therefore, studying the expression and function of irisin in tumors may be of great significance for the prevention and treatment of tumors. This article reviews the research progress on the role of irisin in tumors.

This file includes the data for dune orthomosaic images, grain sizeand relevant materials in manuscript "The Effects of Seasonal Wind Regimes on the Evolution of Reversing Barchanoid Dunes"&nbsp

The function of the N6-methyladenosine (m6A) methyltransferase RNA-binding motif protein 15 (RBM15) in hepatocellular carcinoma (HCC) has not been thoroughly investigated. Here we determined the clinical value, biological functions, and potential mechanisms of RBM15 in HCC. Expression of RBM15 was identified using tissue microarrays and online databases. A risk-prediction model based on RBM15 was developed and validated. We determined the biological role of RBM15 on HCC cells in vitro and in vivo. RNA sequencing was used to screen candidate targets of RBM15. Subsequently, the m6A dot blot assay, methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, RNA decay assay, and RNA immunoprecipitation qPCR were employed to explore the mechanisms of RBM15. Our study showed that RBM15 was highly expressed in HCC, and overexpression of RBM15 indicated a worse outcome. A new nomogram combining RBM15 with age and TNM stage was developed and validated to predict the outcome of HCC patients; our nomogram increased the prediction accuracy of the TNM system. Functionally, RBM15 facilitates the proliferation and invasiveness of HCC. RBM15-mediated m6A modification contributed to a post-transcriptional activation of YES proto-oncogene 1 (YES1) in an insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)-dependent manner. In addition, YES1 was confirmed as an oncogene in HCC cells by activating the mitogen-activated protein kinase (MAPK) pathway. In conclusion, RBM15-mediated m6A modification might facilitate the progression of HCC via the IGF2BP1–YES1–MAPK axis. RBM15 may be a promising biomarker in the outcome prediction of HCC.

Introduction Irisin is a newly identified cytokine that has gained increasing attention because of its potential therapeutic applications in metabolic diseases and human cancers. Recently, accumulating evidence indicates that irisin plays an important role in the development and metastasis of various tumors. The aim of this study was to evaluate the effects and underlying mechanisms of irisin on malignant growth of pancreatic cancer cells. Materials and methods The anti-proliferative effect of irisin was examined using the CCK-8 assay. Irisin-induced apoptosis was determined by the annexin V-FITC/PI staining assay. The effects of irisin on cell migration and invasion were assessed using the scratch-induced wound healing assay and transwell invasion assay, respectively. The expression and phosphorylation of signaling proteins were detected by Western blot analysis. Results Our results showed that irisin inhibited cell proliferation and induced apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, irisin decreased the migration and invasion of pancreatic cancer cells. Finally, Western blot analysis revealed that irisin downregulated the PI3K/AKT signaling pathway. Conclusion Our findings suggest that irisin is a novel therapeutic agent for pancreatic cancer.

This paper presents the environmental history and its responses to palaeoclimatic changes since the start of the Holocene in the eastern portion of the desert belt (sand seas and sandy lands) in northern China by comparing the aeolian sand-palaeosol sequences and their palaeoclimatic proxies. The optically stimulated luminescence (OSL) ages of the aeolian sand-palaeosol sedimentary sequences and a series of palaeoenvironmental proxies show that: (1) The large-scale dune landscape currently in the Kubuqi Sand Sea was formed during the Holocene in general; and the palaeosol was generally developed during the period of 4–2 ka, indicating conditions favorable for vegetation growth, soil development, and organic carbon accumulation due to increased precipitation or effective moisture and weakened aeolian activities; the large-scale expansion of dunes in the recent 2 ka is closely linked to human activities. The variable discharge of the Yellow River with diversions for irrigation may have resulted in a more consistent supply of aeolian particles for dune field expansion. (2) The dune landscape of the Hunshandake Sandy Land was likely formed around 12 ka, and before this, the western part of the Hunshandake Sandy Land would have been covered by a single large lake; it was obviously wetter than today in the sandy land during the period of 9.6–3 ka and the palaeosols were developed at the same time. But the aeolian activities have not been completely dormant in this long-lasting wetter epoch; because the Holocene wetter period was likely time-transgressive across the region. (3) The palaeosol of the Hulunbuir Sandy Land began to develop as early as 14.5 ka, probably continuing until the last 2 ka. The palaeosol development of various dune fields in the eastern portion of the desert belt (sand seas and sandy lands) in northern China is spatially heterogeneous, and even the palaeosol development time in different locations within each sandy land is inconsistent. During the middle Holocene (especially the 7.5–3.5 ka), all the sandy lands were stabilized in general and the intensity of aeolian activities was significantly weakened. The number of palaeoenvironmental records in the eastern portion of the desert belt (sand seas and sandy lands) in northern China has increased rapidly in the past decade, but the amount of published data still does not match the vast extent of the dune fields. It does require much more in-depth palaeoenvironmental studies for a full understanding of the relationship between aeolian activities and climate change in northern China.

Circular RNAs (circRNA) and N6-methyladenosine (m6A) modification are extensively involved in the progression of diverse tumors, including hepatocellular carcinoma (HCC). However, the cross-talk between circRNAs and m6A remains elusive in the pathogenesis of HCC. Here we investigated m6A-mediated regulation of circRNAs in HCC. m6A-related circRNAs were identified by integrating information from two published studies, revealing circular cleavage and polyadenylation specific factor 6 (circCPSF6) as a novel m6A-modified circRNA. circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated circCPSF6 expression served as an independent prognostic factor for worse survival of patients with HCC. Loss-of-function assays demonstrated that circCPSF6 maintained cell proliferation and tumorigenicity and reinforced cell motility and tumor metastasis. circCPSF6 triggered expression of YAP1, further activating its downstream cascade. Mechanistically, circCPSF6 competitively bound PCBP2, blunting its binding to YAP1 mRNA, thereby sustaining the stability of YAP1. Functionally, removal of YAP1 reversed the effects of circCPSF6 in vitro and in vivo. Aberrant activation of the circCPSF6-YAP1 axis promoted HCC malignancy. These findings offer novel insights into the regulation of circRNAs by m6A modifications and the role of this epigenetic reprogramming in HCC. Significance: This study advances the understanding of the interplay between m6A methylation and circRNAs in hepatocellular carcinoma, highlighting the potential of circCPSF6 as a therapeutic target.

Irisin is a newly discovered exercise-induced cytokine, produced by the proteolytic hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Irisin is widely distributed in the human body and is involved in the browning of white adipose tissue, improving insulin resistance, improving cognitive function, and regulating bone metabolism. Recent studies have shown that irisin concentration is elevated in a variety of tumor tissues as compared with that in normal tissues. However, irisin has different effects on the proliferation and apoptosis of tumor cells in breast cancer, lung cancer, and liver cancer through various mechanisms. Irisin plays an important role in the occurrence, development, and metastasis of different tumors, suggesting that irisin can be used as a potential target for tumor diagnosis and treatment. Therefore, studying the expression and function of irisin in tumors may be of great significance for the prevention and treatment of tumors. This article reviews the research progress on the role of irisin in tumors.

Desertification is a key environmental concern in arid and semi-arid regions. The sedimentological and geochemical characteristics of sediments are closely related to desertification processes, but the relationship between them is still unclear. This study aimed to identify the sedimentological and geochemical characteristics of different sediments in the Taklamakan Desert and to monitor changes in sediment composition as the intensity of desertification varied in the last decades. We examined the grain size, major, trace and rare earth elements of surface sediments collected from loess, sandy loess, fluvial sands, vegetated dunes and mobile dunes along the Keriya River in the Taklamakan Desert. Major element analysis found that loess had the highest degree of chemical weathering, while weathering of surface sediments on dunes (both mobile and vegetated ones) was relatively weak. Trace and rare earth element analysis found sediments were mainly derived from the West Kunlun and West Tianshan Mountains. This study also analyzed vegetation and wind data from 2000 to 2018 and found that the intensity of desertification processes weakened. The near-surface mean wind speed also decreased from 2000 to 2018, resulting in an increase in both the grain size of aeolian sediments on the surface of mobile dunes and the degree of chemical weathering. Additionally, this study confirmed that clay-sized components can be carried by high-altitude westerlies or formed by pedogenesis. With the strengthening of westerlies and the increase of chemical weathering, it is likely that more clay components will be added to the loess located on the northern slope of the Kunlun Mountains. This study demonstrates that the landscape evolution of the Keriya River in the Taklamakan Desert is primarily driven by fluvial processes, vegetation and wind dynamics, and that these processes may be affected by the intensity of desertification.

The Kubuqi Desert is the only active sand sea in the semiarid regions of northern China and occurs along the southern margin of the Yellow River. Little is known about the age and origin of this large (17,000 km2) sand sea with a present annual precipitation of 200‐480 mm. Sand drift potentials indicated net capable winds for aeolian transport are from the northwest, though winds are stronger to north beyond the dune field than within the sand sea. Geomorphic and stratigraphic observations indicate that Holocene aeolian sand often drapes over bedrock and river terraces as a palimpsest landscape. Field investigations identified four stratigraphic sections with multiple aeolian sand units and palaeosols, with age control by optically stimulated luminescence (OSL) dating of quartz grains. Palaeosols are weakly developed, mostly accumulative A horizon with organic carbon content

In the middle-to-late Holocene, Earth's monsoonal regions experienced catastrophic precipitation decreases that produced green to desert state shifts. Resulting hydrologic regime change negatively impacted water availability and Neolithic cultures. Whereas mid-Holocene drying is commonly attributed to slow insolation reduction and subsequent nonlinear vegetation-atmosphere feedbacks that produce threshold conditions, evidence of trigger events initiating state switching has remained elusive. Here we document a threshold event ca. 4,200 years ago in the Hunshandake Sandy Lands of Inner Mongolia, northern China, associated with groundwater capture by the Xilamulun River. This process initiated a sudden and irreversible region-wide hydrologic event that exacerbated the desertification of the Hunshandake, resulting in post-Humid Period mass migration of northern China's Neolithic cultures. The Hunshandake remains arid and is unlikely, even with massive rehabilitation efforts, to revert back to green conditions.

Irisin is a newly identified myokine that may be cancer-associated, and its impact on liver cancer is unclear. To understand the roles of irisin in liver cancer, we investigated its effect in HepG2 and SMCC7721 hepatocellular carcinoma cells, and the underlying mechanisms. We determined irisin levels in liver tissues and serum samples obtained from patients by using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Irisin levels in cancerous livers were significantly upregulated compared with those in control livers, but serum irisin levels remained unchanged. Additionally, we evaluated the effects of different concentrations of human recombinant modified and active (glycosylated) irisin (IM) or human recombinant nonmodified irisin (INM) on cell migration, proliferation, viability, and invasiveness. CCK8, transwell, and scratching assays demonstrated that irisin significantly increased cell proliferation, invasion, and migration through activation of the PI3K/AKT pathway. Irisin-induced cell proliferation, migration, and invasion were blocked by a PI3K inhibitor (LY294002). Irisin also decreased the cytotoxicity of doxorubicin in HepG2 cells. These data indicate that increased irisin levels may have protective roles in liver cancer cells through partial activation of the PI3K/AKT pathway, which may facilitate liver cancer progression and decrease the sensitivity to chemotherapy.

Identification of aeolian sand sources occurring in oases of desert environments is of great importance for understanding desertification processes and for developing strategies for sustainable development in arid regions. Combined with wind data and hierarchical cluster analysis, we analyzed the spatial characteristics of major and trace elements of sands sampled at the margins of the Minqin Oasis, northwestern China and its adjacent deserts (the Badain Jaran Desert and the Tengger Desert), with the purpose to identify the aeolian sand sources and their transport pathways in the region. The spatial distribution revealed by bivariate plots of Cr, Ni, Cr/V, Y/Ni, Al, V, Zr, Hf, Zr/Hf and ternary plots of major and trace elements showed that sands between the west (B - Badain Jaran Desert, BM - the dune belt between Badain Jaran and the Minqin Oasis and TNE - dune field located in the northeast margin of the Minqin Oasis) and southeast (TSW - dune field located in the southeast margin of the Minqin Oasis) sides of the oasis have different provenances, while the composition of sands in the Minqin Oasis (M) and in the dune field located in the south margin (TM) is associated with both. The variations in abundance of K, Rb, Ba and Sr were used as indicators of aeolian transport processes. Our results show that while aeolian sands from the Badain Jaran Desert can be transported over mountains and over long distances by northwest winds to the west sides of the Minqin Oasis, they cannot directly reach neither bypass the oasis to the east side. Our interpretation is that the oasis can act as an effective barrier to stop the migration of dune fields both in the Badain Jaran Desert and the Tengger Desert. However, the extensive occurrence of aeolian sands in the Minqin Oasis indicates that its role in preventing desert encroachment should not be overestimated. (C) 2014 Elsevier Ltd and INQUA. All rights reserved.

Sedimentary sequences occurring in desert dunes reflect changes in desert systems, and as such may contain signals useful for recognizing spatial and temporal changes of deserts and their response to regional or even global climate fluctuations. Geomorphological and palaeoenvironmental studies within the dune fields of the Asian middle-latitudes have provided some solid evidence for interpreting the history of these sand seas. Using the Hunshandake (Otindag) Sandy Land, a sandy area covered primarily by stabilized dunes and located in the semi-arid zone of eastern Inner Mongolia, China (Fig. 1), as an example, we studied the initiation and variation in the dune landscape in the eastern portion of the desert belt in northern China. On the basis of physical and biochemical indicators in the sediments and OSL chronology, we herein argue that this dune system in the middle latitudes of eastern Asia is much younger than previously assumed and that it has responded sensitively to climate change during the late Quaternary. Geological evidence from the Sandy Land suggests that most of the current dunes are of late Pleistocene or even Holocene age. Palaeosols intercalated in the aeolian sequences and their OSL chronology show that the climate of the Hunshandake was much wetter than today between 9.6 ka and 3 ka. This resulted in stabilization of the dunes in the eastern and central portions of the Sandy Land. Epochs of reworking or stabilization of the dunes are broadly consistent with the fluctuations in northern hemisphere solar radiation although with an obvious time lag. Because the increase rate of annual precipitation was not sufficient to fully stabilize the dunes in more arid part of the region, some active dunes persisted even during this long-lasting wetter epoch. We conclude that periods of Holocene dune stabilization due to palaeosol formation varied along the climate gradients across the various sandy lands of northern China, and in general it began earlier and lasted longer in the east than in the west. The general nature of the sandy lands and their counterparts in the western portion of the desert belt during the LGM and mid-Holocene climate optimum is discussed in comparison with their current states.