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Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in cancer, however, posttranscriptional regulation such as N6-methyladenosine (m6A) of IGF1Rremains unclear. Here, we reveal a role for a lncRNA Downregulated RNA in Cancer(DRAIC)suppress tumor growth and metastasis in clear cell Renal Carcinoma (ccRCC). Mechanistically, DRAICphysically interacts with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and enhances its protein stability by blocking E3 ligase F-box protein 11 (FBXO11)-mediated ubiquitination and proteasome-dependent degradation. Subsequently, hnRNPA2B1 destabilizes m6A modified-IGF1R, leading to inhibition of ccRCC progression. Moreover, four m6A modification sites are identified to be responsible for the mRNA degradation of IGF1R. Collectively, our findings reveal that DRAIC/hnRNPA2B1 axis regulates IGF1RmRNA stability in an m6A-dependent manner and highlights an important mechanism of IGF1R fate. These findings shed light on DRAIC/hnRNPA2B1/FBXO11/IGF1Raxis as potential therapeutic targets in ccRCC and build a link of molecular fate between m6A-modified RNA and ubiquitin-modified protein.

Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR−/−mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivoelectrophysiological technique was used to record LPBN glucose-sensitive neurons to explore potential udnderlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 h, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR−/−mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GE and GI neurons.

The formation and evolution of permafrost in China during the last 20 ka were reconstructed on the basis of large amount of paleo-permafrost remains and paleo-periglacial evidence, as well as paleo-glacial landforms, paleo-flora and paleofauna records. The results indicate that, during the local Last Glacial Maximum (LLGM) or local Last Permafrost Maximum (LLPMax), the extent of permafrost of China reached 5.3×106−5.4×106km2, or thrice that of today, but permafrost shrank to only 0.80×106−0.85×106km2, or 50% that of present, during the local Holocene Megathermal Period (LHMP), or the local Last Permafrost Minimum (LLPMin). On the basis of the dating of periglacial remains and their distributive features, the extent of permafrost in China was delineated for the two periods of LLGM (LLPMax) and LHMP (LLPMin), and the evolution of permafrost in China was divided into seven periods as follows: (1) LLGM in Late Pleistocene (ca. 20000 to 13000−10800 a BP) with extensive evidence for the presence of intensive ice-wedge expansion for outlining its LLPMax extent; (2) A period of dramatically changing climate during the early Holocene (10800 to 8500−7000 a BP) when permafrost remained relatively stable but with a general trend of shrinking areal extent; (3) The LHMP in the Mid-Holocene (8500−7000 to 4000−3000 a BP) when permafrost degraded intensively and extensively, and shrank to the LLPMin; (4) Neoglaciation during the late Holocene (4000−3000 to 1000 a BP, when permafrost again expanded; (5) Medieval Warming Period (MWP) in the late Holocene (1000−500 a BP) when permafrost was in a relative decline; (6) Little Ice Age (LIA) in the late Holocene (500−100 a BP), when permafrost relatively expanded, and; (7) Recent warming (during the 20th century), when permafrost continuously degraded and still is degrading. The paleo-climate, geography and paleopermafrost extents and other features were reconstructed for each of these seven periods.

In modern pesticide discovery, target-based drug design is an attractive and cost-effective approach. Previous studies found that protein rootletin (PcRoo) is a target protein of arecoline, when interacted with Pomacea canaliculata. In this study, we modeled the target protein through threading, and the binding energy between arecoline and protein PcRoo was calculated as −5.02 kcal/mol by molecular docking. Furthermore, two target compounds, baclofen and acedoben, with molluscicidal activity in theory were obtained by virtual screening in database DrugBank. The in vivobioassay showed that baclofen could induce typical poisoning symptoms on P. canaliculata, which were characterized by weakness of foot muscles and loss of gill cilia, and the LC50value was 16.2437 mg/L (72 h). Additionally, after 15 mg/L baclofen treatment, the oxygen consumption rate, ammonia excretion rate, and oxygen nitrogen ratio of P. canaliculatadeclined. Furthermore, the treatment of baclofen also decreased the gene expression level of PcRoo. These trends were the same as the changes after 5 mg/L arecoline treatment. The pharmacophore characteristics were further analyzed, and the results showed that the chemical structures of baclofen and arecoline were correlated in molluscicidal activity. These findings indicate that baclofen has the potential to be used as a molluscicide in agricultural production, and other new molluscicides may be obtained by virtual screening based on protein PcRoo.

Forest canopy in a deciduous forest has significant sheltering effects on the sub-canopy solar radiation, significantly influencing the energy balance of snow and permafrost beneath the forest and their spatial distribution. This study employs a digital camera mounted with a fisheye lens to acquire photographs at various times in a growth cycle of the forest canopy at three selected sites in a deciduous forest near the Greater Khingan Mountains Forest Ecological Station, Northeast China. The vegetation types and conditions at the selected sites include P1 in Ledum-Claopodium-L. dahurica, P2 in Carex tato-L. dahurica, and P3 in Betula fruticosa-L. dahurica. After necessary image processing, these photographs were used to identify the canopy structure and its impacts on the sub-canopy solar radiation. Results show that fisheye photographs can successfully capture the forest canopy structure and are useful in estimating the sub-canopy solar radiation. The order of sheltering effects from the largest to the smallest on sub-canopy solar radiation at three selected sites is P3, P1, and P2, highly depending on the canopy density. Then sub-canopy solar radiation was calculated using fisheye photographs and an algorithm validated by in-situ observed solar radiation beneath the canopy at P1 and P3. The results are reasonable, although the accuracy seems compromised due to the mismatch of conditions for calculation and observation. Results also show that the mean annual solar radiation above the canopy was about 148.3 W/m2in 2018, and the mean annual solar radiation values beneath the canopy were about 90.0, 123.8, and 61.0 W/m2at P1, P2, and P3, with only 60%, 84%, and 42% of the total solar radiation penetrating through the canopy, respectively. Even in winter, when the trees are leafless, the canopy sheltering effects cannot be ignored in dense forests. Despite the limitations, fisheye photographs and related algorithms are useful in investigating the forest canopy structure and its impacts on sub-canopy solar radiation.

AbstractA comprehensive observing system was established at the Da Xing'anling (Hinggan) Mountains Station (Gen'he) of China Forest Ecological Research Network (CFERN) in Northeast China in 2009 and gradually improved since in order to evaluate the influences of boreal forest vegetation with complex structures and various components on the thermal regimes of active layer and shallow permafrost soils. At three selected typical forest sites with similar micro-reliefs, soils, and drainage conditions, the soil temperatures on the ground surface and at various depths ranging from 0.05 to 5.0 m were measured with thermistor cables permanently installed in boreholes. The temperature data were compared and contrasted for various vegetative features. In a control experiment, trees and shrubs were removed to better understand the hydrothermal effects of vegetation removal. Results show that: (1) The vegetative layer provides an evident effect of thermal insulation on the ground. The ground temperature at the same depth was lower at a stand with denser vegetation when other conditions are held the same. (2) The ground warms up when the vegetation degrades, and the ground temperature rises from the vegetation degradation could reach much deeper in winter than in summer. (3) In cases of extensive vegetation degradation, the resultant ground warming persists for a long time, resulting in a deepening active layer.

Abstract: Northeastern China has the second largest expanse of permafrost in China, primarily known as Xing’an-Baikal permafrost. Located on the southeastern edges of the Eurasian cryolithozone, the permafrost is thermally unstable and ecologically sensitive to external changes. The combined impacts of climatic, environmental, and anthropogenic changes cause 3-dimensional degradation of the permafrost. To predict these changes on the southern limit and ground temperature of permafrost in Northeastern China, an equivalent latitude model (ELM) for the mean annual ground surface temperature (MAGSTs) was proposed, and further improved to take into account of the influences of vegetation and snow-cover based on observational data and using the SHAW model. Using the finite element method and assuming a climate warming rate of 0.048°C a−1, the ELM was combined with the unsteady-state heat conduction model to simulate permafrost temperatures at present, and to predict those after 50 and 100 a. The results indicate that at present, sporadic permafrost occurs in the zones with MAGSTs of 1.5°C or colder, and there would still be a significant presence of permafrost in the zones with the present MAGSTs of 0.5°C or colder after 50 a, and in those of −0.5°C or colder after 100 a. Furthermore, the total areal extent of permafrost would decrease from 2.57×105 km2 at present to 1.84×105 km2 after 50 a and to 1.29×105 km2 after 100 a, i.e., a reduction of 28.4% and 49.8% in the permafrost area, respectively. Also the permafrost would degrade more substantially in the east than in the west. Regional warming and thinning of permafrost would also occur. The area of stable permafrost (mean annual ground temperature, or MAGT⩽−1.0°C) would decrease from present 1.07×105 to 8.8×104 km2 after 50 a, and further decrease to 5.6×104 km2 after 100 a. As a result, the unstable permafrost and seasonally frozen ground would expand, and the southern limit of permafrost would shift significantly northwards. The changes in the permafrost environment may adversely affect on ecological environments and engineering infrastructures in cold regions. Avoidance of unnecessary anthropogenic changes in permafrost conditions is a practical approach to protect the permafrost environment.

Ibrutinib in combination with rituximab and high-dose methotrexate in newly diagnosed primary central nervous system lymphoma patients

No relevant conflicts of interest to declare.

Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.