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Lung cancer is one of the leading causes of death among cancer patients worldwide. Carbon-ion radiotherapy is a radical nonsurgical treatment with high local control rates and no serious adverse events. N6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic messenger RNA (mRNA) and has important effects on the stability, splicing, and translation of mRNAs. Recently, the regulatory role of m6A in tumorigenesis has been recognized more and more. However, the dysregulation of m6A and its role in carbon-ion radiotherapy of non-small-cell lung cancer (NSCLC) remains unclear. In this study, we found that the level of methyltransferase-like 3 (METTL3) and its mediated m6A modification were elevated in NSCLC cells with carbon-ion radiotherapy. Knockdown of METTL3 in NSCLC cells impaired proliferation, migration, and invasion in vitro and in vivo. Moreover, we found that METTL3-mediated m6A modification of mRNA inhibited the decay of H2A histone family member X (H2AX) mRNA and enhanced its expression, which led to enhanced DNA damage repair and cell survival.

Algal blooms (ABs) in inland lakes have caused adverse ecological effects, and health impairment of animals and humans. We used archived Landsat images to examine ABs in lakes (>1 km2) around the globe over a 37-year time span (1982–2018). Out of the 176032 lakes with area >1 km2 detected globally, 863 were impacted by ABs, 708 had sufficiently long records to define a trend, and 66% exhibited increasing trends in frequency ratio (FRQR, ratio of the number of ABs events observed in a year in a given lake to the number of available Landsat images for that lake) or area ratio (AR, ratio of annual maximum area covered by ABs observed in a lake to the surface area of that lake), while 34% showed a decreasing trend. Across North America, an intensification of ABs severity was observed for FRQR (p

Reduced generation of multiple motile cilia (RGMC) and the consequent primary ciliary dyskinesia (PCD) cause infertility due to a substantial reduction in the number of multiciliated cells (MCCs) in the efferent ducts (EDs)/oviducts. MCIDAS acts upstream of CCNO to regulate the biogenesis of basal bodies (BBs); therefore, both genes play a vital role in the multiciliogenesis of the reproductive tract epithelium. In this study, whole-exome sequencing was performed to identify the causative genes in ten unrelated infertile patients with PCD: seven males and three females. Notably, homozygous frameshift mutations in MCIDAS (c.186dupT, p.Pro63Serfs*22) and CCNO (c.262_263insGGCCC, p.Gln88Argfs*8) were identified in one male and one female participant from two unrelated consanguineous families. Haematoxylin-eosin staining/scanning electron microscopy revealed abnormal MCCs in the mutated EDs/oviducts. Furthermore, transmission electron microscopy revealed significantly reduced BBs. Immunofluorescence staining showed the absence of MCIDAS and CCNO signals in the affected tissues and confirmed that MCIDAS acts upstream of CCNO in the context of multiciliogenesis in the reproductive tract epithelium. In vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) was successful, with a positive pregnancy outcome in both MCIDAS- and CCNO-mutated patients. Our results support the use of IVF/ICSI interventions to treat infertility due to RGMC in couples.

Hypoxia is a risk factor for Alzheimer's disease (AD). Besides, mitochondrial fission is increased in response to hypoxia. In this study, we sought to investigate whether hypoxia‐induced mitochondrial fission plays a critical role in regulating amyloid‐β (Aβ) production. Hypoxia significantly activated extracellular signal‐regulated kinase (ERK), increased phosphorylation of dynamin‐related protein 1 (Drp1) at serine 616, and decreased phosphorylation of Drp1 at serine 637. Importantly, hypoxia triggered mitochondrial dysfunction, elevated β‐secretase 1 (BACE1) and γ‐secretase activities, and promoted Aβ accumulation in HEK293 cells transfected with β‐amyloid precursor protein (APP) plasmid harboring the Swedish and Indiana familial Alzheimer's disease mutations (APPSwe/Ind HEK293 cells). Then, we investigated whether the ERK inhibitor PD325901 and Drp1 inhibitor mitochondrial division inhibitor‐1 (Mdivi‐1) would attenuate hypoxia‐induced mitochondrial fission and Aβ generation in APPSwe/Ind HEK293 cells. PD325901 and Mdivi‐1 inhibited phosphorylation of Drp1 at serine 616, resulting in reduced mitochondrial fission under hypoxia. Furthermore, hypoxia‐induced mitochondrial dysfunction, BACE1 activation, and Aβ accumulation were downregulated by PD325901 and Mdivi‐1. Our data demonstrate that hypoxia induces mitochondrial fission, impairs mitochondrial function, and facilitates Aβ generation. The ERK–Drp1 signaling pathway is partly involved in the hypoxia‐induced Aβ generation by regulating mitochondrial fission and BACE1 activity. Therefore, inhibition of hypoxia‐induced mitochondrial fission may prevent or slow the progression of AD., Hypoxia is a risk factor for Alzheimer's disease. However, whether hypoxia‐induced mitochondrial fission plays a critical role in the regulation of amyloid‐β (Aβ) accumulation has not yet been investigated. In the current study, we show that the ERK/Drp1 signaling pathway is partly involved in regulating mitochondrial fission and Aβ generation under hypoxia.

Seasonality is a key feature of the biosphere and the seasonal dynamics of soil carbon (C) emissions represent a fundamental mechanism regulating the terrestrial-climate interaction. We applied a microbial explicit model-CLM-Microbe-to evaluate the impacts of microbial seasonality on soil C cycling in terrestrial ecosystems. The CLM-Microbe model was validated in simulating belowground respiratory fluxes, that is, microbial respiration, root respiration, and soil respiration at the site level. On average, the CLM-Microbe model explained 72% (n = 19, p < 0.0001), 65% (n = 19, p < 0.0001), and 71% (n = 18, p < 0.0001) of the variation in microbial respiration, root respiration, and soil respiration, respectively. We then compared the model simulations of soil respiratory fluxes and soil organic C content in top 1 m between the CLM-Microbe model with (CLM-Microbe) and without (CLM-Microbe_wos) seasonal dynamics of soil microbial biomass in natural biomes. Removing soil microbial seasonality reduced model performance in simulating microbial respiration and soil respiration, but led to slight differences in simulating root respiration. Compared with the CLM-Microbe, the CLM-Microbe_wos underestimated the annual flux of microbial respiration by 0.6%-32% and annual flux of soil respiration by 0.4%-29% in natural biomes. Correspondingly, the CLM-Microbe_wos estimated higher soil organic C content in top 1 m (0.2%-7%) except for the sites in Arctic and boreal regions. Our findings suggest that soil microbial seasonality enhances soil respiratory C emissions, leading to a decline in SOC storage. An explicit representation of soil microbial seasonality represents a critical improvement for projecting soil C decomposition and reducing the uncertainties in global C cycle projection under the changing climate.

AIMS: Soil dissolved organic carbon (DOC) is a primary form of labile carbon in terrestrial ecosystems, and therefore plays a vital role in soil carbon cycling. This study aims to quantify the budgets of soil DOC at biome and global levels and to examine the variations in soil DOC and their environmental controls. LOCATION: Global. TIME PERIOD: 1981–2019. METHODS: We compiled a global dataset and analysed the concentration and distribution of DOC across 10 biomes. RESULTS: Large variations in DOC are found among biomes across space and the soil DOC concentration declines exponentially along soil depths. Tundra has the highest soil DOC concentration in 0–30 cm soils [453.75 (95% confidence interval: 324.95–633.5) mg/kg], whereas tropical and temperate forests have relatively lower DOC concentrations, ranging from 30.20 (24.78–36.80) to 54.54 (49.77–59.77) mg/kg. DOC generally accounts for

In recent years, China has promoted many new energy projects in order to meet the growing demand for electricity. Therefore, China's offshore wind power installed capacity has grown rapidly. China has a long coastline and abundant offshore wind energy resources. Offshore wind power is an important area for the development of renewable energy, which can promote wind power technology advancement and energy structure adjustment. Therefore, conducting effective research and forecast on the cumulative installed capacity of China's offshore wind power will help the government to rationally deploy and reduce the risk of investment in offshore wind power. In order to accurately predict the future prospects of offshore wind power in China, this paper firstly constructed a set of influencing factors and used gray correlation analysis to screen the main influencing factors. Then, this paper proposed a novel forecasting model named e‐VMD‐PCA‐RELM. The algorithm is based on the traditional RELM (robust extreme learning machine) algorithm, which effectively processes the noise information through the PCA (principal component analysis) algorithm, and extracted the feature elements of the RELM hidden layer to reduce the information redundancy. At the same time, the e‐VMD (variational mode decomposition optimized by entropy) algorithm is used to decompose the original time series to obtain multiple components. By comparing with the other forecasting algorithms, it is proved that the proposed forecasting model has strong generalization ability and has achieved good prediction result. Finally, the e‐VMD‐PCA‐RELM model is used to predict the scale of offshore wind farms in China from 2019 to 2035. We find that the cumulative installed capacity of China's offshore wind power will exceed 60 GW in 2035, and the installed capacity will increase year by year. In 2030, there will be a large increase, with a relative growth rate of 20%.

Grassland ecosystems account for more than 10% of the global CH4 sink in soils. A 4-year field experiment found that addition of P alone did not affect CH4 uptake and experimental addition of N alone significantly suppressed CH4 uptake, whereas concurrent N and P additions suppressed CH4 uptake to a lesser degree. A meta-analysis including 382 data points in global grasslands corroborated these findings. Global extrapolation with an empirical modelling approach estimated that contemporary N addition suppresses CH4 sink in global grassland by 11.4% and concurrent N and P deposition alleviates this suppression to 5.8%. The P alleviation of N-suppressed CH4 sink is primarily attributed to substrate competition, defined as the competition between ammonium and CH4 for the methane mono-oxygenase enzyme. The N and P impacts on CH4 uptake indicate that projected increases in N and P depositions might substantially affect CH4 uptake and alter the global CH4 cycle.

Neural progenitor cells (NPCs) are sequentially specified into neurons and glia during the development of central nervous system. WNT/β-catenin signaling is known to regulate the balance between the proliferation and differentiation of NPCs during neurogenesis. However, the function of WNT/β-catenin signaling during gliogenesis remains poorly defined. Here, we report that activation of WNT/β-catenin signaling disrupts astrogliogenesis in the developing spinal cord. Conversely, inhibition of WNT/β-catenin signaling leads to precocious astrogliogenesis. Further analysis reveals that activation of WNT/β-catenin pathway results in a dramatic increase of neurogenin 2 (Ngn2) expression in transgenic mice, and knockdown of Ngn2 expression in neural precursor cells can reverse the inhibitory effect of WNT/β-catenin on astrocytic differentiation. Moreover, Ngn2 can directly bind to the promoters of several astrocyte specific genes and suppress their expression independent of STATs activity. Together, our studies provide the first in vivo evidence that WNT/β-catenin signaling inhibits early astrogliogenesis via an Ngn2-dependent transcriptional repression mechanism.

The triboelectric nanogenerator (TENG) is an emerging technology that offers excellent potential for the conversion of mechanical energy from rain into electricity for hybrid energy applications. However, a high-performance TENG is yet to be achieved because a quantitative analysis method for the energy conversion process is still lacking. Herein, a quantitative analysis method, termed the "kinetic energy calculation and current integration" (KECCI) method, which significantly improves the understanding of the mechanical-to-electrical energy conversion process, is presented. Based on the KECCI method, a high-performance TENG is developed by systematically optimizing a biomimetic surface structure and instant switch design, with 1.25 mA short-circuit current (I

Gastric cancer (GC) is one of the main causes of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) is an important biological process involving the process by which malignant tumor cells obtain the ability of migration, invasion, resistance of apoptosis, and degradation in the extracellular matrix. The current study aimed at investigating whether bone marrow X kinase Rho GTPase activating protein 12 (BMX-ARHGAP) fusion gene affects GC. First, short hairpin RNA (shRNA) against BMX-ARHGAP or BMX-ARHGAP were introduced to treat SGC-7901 cells with the highest BMX-ARHGAP among the five GC cell lines (SGC-7901, MKN-45, NCI-N87, SNU-5, and AGS). Next, cell vitality, drug resistance, migration, and invasion of SGC-7901 cells, activities of Rho and JAK/STAT axis, as well as EMT and lymph node metastasis (LNM) were evaluated. The survival rate of the mice was then determined through the transfection of the specific pathogen-free NOD-SCID mice with treated SGC-7901 cells. The results showed that BMX-ARHGAP expression was associated with the infiltration degree of GC tumor and poor prognosis for patients with GC. BMX-ARHGAP silencing was found to play an inhibitory role in the Rho and JAK/STAT axis to reduce cell vitality, drug resistance, migration and invasion, reverse EMT process, as well as inhibit LNM. BMX-ARHGAP overexpression was observed to have induced effects on GC cells as opposed to those inhibited by BMX-ARHGAP silencing. The survival rate of mice was increased after transfection with silenced BMX-ARHGAP. These findings provided evidence that the suppression of BMX-ARHGAP resulted in the inhibition of RhoA to restraint the development of GC cells by blocking the JAK/STAT axis.

Nitrogen (N) ammonification and nitrification are two primary microbial processes controlling the availability of soil ammonium (NH4+), a key nutrient for vegetative growth. The large-scale patterns of gross ammonification (GA) and gross nitrification (GN) rates represent soil microbial adaptations to different vegetative and environmental conditions. In this study, we investigated GA and GN rates in nine forest soils along a 3,700-km north–south transect in eastern China. We used 15N-labelling techniques, along with field experiments and laboratory incubations, to assess in situ and potential rates of the GA and GN. The mean in situ GA rate was 4.9 ± 0.5 mg N kg−1 day−1, whereas the mean potential rate of GA was 32.0 ± 8.6 mg N kg−1 day−1. The mean in situ GN rate was 1.7 ± 0.3 mg N kg−1 day−1 (potential GN rate: 3.2 ± 0.6 mg N kg−1 day−1). GA was significantly higher than GN along the transect, and there were high variations in GA and GN among different forests. Significant relationships were identified between meteorological factors (temperature and precipitation) and the GA and GN rates during the sampling month (August 2013). However, the mean GA rate in primary forest was significantly lower in the Huzhong (HZ), Dongling (DL), Taiyue (TY) and Dinghu (DH) sites compared with other sites, whereas with the exception of the Liangshui (LS) sampling site, the mean GN rate in primary and secondary forests showed the same trends. Significant differences in GA rates were found between primary and secondary forests at the LS and Changbai (CB) sites, and differences were detected in GN rate at the HZ, LS and Jiulian (JL) sites. Structural equation modelling analysis suggested that soil N contents, microbial biomass N pool sizes and bacterial abundance are the primary determinants of the in situ rates of GA and GN. The strong control of edaphic factors on GA and GN indicates a need to improve soil N models with more explicit representation of edaphic factors and their control on soil N transformations. A plain language summary is available for this article.

Aim Anthropogenic additions of nitrogen (N) are expected to drive terrestrial ecosystems toward greater phosphorus (P) limitation. However, a comprehensive understanding of how an ecosystem's P cycle responds to external N inputs remains elusive, making model predictions of the anthropogenic P limitation and its impacts largely uncertain. Location Global. Time period 1986-2015. Major taxa studied Terrestrial ecosystems. Methods We conducted a meta-analysis including 288 independent study sites from 192 articles to evaluate global patterns and controls of 10 variables associated with ecosystem P cycling under N addition. Results Overall, N addition increased biomass in plants (+34%) and litter (+15%) as well as plant P content (+17%), while decreasing P concentrations in plants and litter (−8% and −11%, respectively). N addition did not change soil labile P or microbial P, but enhanced phosphatase activity (+24%). The effects of N addition on the litter P pool and soil total P remained unclear due to significant publication biases. The response of P cycling to N addition in tropical forests was different from that in other ecosystem types. N addition did not change plant biomass or phosphatase activity in tropical forests but significantly reduced plant P and soil labile P concentrations. The shift in plant P concentration under N addition was negatively correlated with the N application rate or total N load. N-induced change in soil labile P was strongly regulated by soil pH value at the control sites, with a significant decrease of 14% only in acidic soils (pH

The carbon use efficiency of plants (CUEa ) and microorganisms (CUEh ) determines rates of biomass turnover and soil carbon sequestration. We evaluated the hypothesis that CUEa and CUEh counterbalance at a large scale, stabilizing microbial growth (μ) as a fraction of gross primary production (GPP). Collating data from published studies, we correlated annual CUEa , estimated from satellite imagery, with locally determined soil CUEh for 100 globally distributed sites. Ecosystem CUEe , the ratio of net ecosystem production (NEP) to GPP, was estimated for each site using published models. At the ecosystem scale, CUEa and CUEh were inversely related. At the global scale, the apparent temperature sensitivity of CUEh with respect to mean annual temperature (MAT) was similar for organic and mineral soils (0.029°C-1 ). CUEa and CUEe were inversely related to MAT, with apparent sensitivities of -0.009 and -0.032°C-1 , respectively. These trends constrain the ratio μ : GPP (= (CUEa × CUEh )/(1 - CUEe )) with respect to MAT by counterbalancing the apparent temperature sensitivities of the component processes. At the ecosystem scale, the counterbalance is effected by modulating soil organic matter stocks. The results suggest that a μ : GPP value of c. 0.13 is a homeostatic steady state for ecosystem carbon fluxes at a large scale.