Soil CO2 and N2O emissions and microbial abundances altered by temperature rise and nitrogen addition in active-layer soils of permafrost peatland

Changes in soil CO2 and N2O emissions due to climate change and nitrogen input will result in increased levels of atmospheric CO2 and N2O, thereby feeding back into Earth’s climate. Understanding the responses of soil carbon and nitrogen emissions mediated by microbe from permafrost peatland to temperature rising is important for modeling the regional carbon and nitrogen balance. This study conducted a laboratory incubation experiment at 15 and 20°C to observe the impact of increasing temperature on soil CO2 and N2O emissions and soil microbial abundances in permafrost peatland. An NH4NO3 solution was added to soil at a concentration of 50 mg N kg−1 to investigate the effect of nitrogen addition. The results indicated that elevated temperature, available nitrogen, and their combined effects significantly increased CO2 and N2O emissions in permafrost peatland. However, the temperature sensitivities of soil CO2 and N2O emissions were not affected by nitrogen addition. Warming significantly increased the abundances of methanogens, methanotrophs, and nirK-type denitrifiers, and the contents of soil dissolved organic carbon (DOC) and ammonia nitrogen, whereas nirS-type denitrifiers, β-1,4-glucosidase (βG), cellobiohydrolase (CBH), and acid phosphatase (AP) activities significantly decreased. Nitrogen addition significantly increased soil nirS-type denitrifiers abundances, β-1,4-N- acetylglucosaminidase (NAG) activities, and ammonia nitrogen and nitrate nitrogen contents, but significantly reduced bacterial, methanogen abundances, CBH, and AP activities. A rising temperature and nitrogen addition had synergistic effects on soil fungal and methanotroph abundances, NAG activities, and DOC and DON contents. Soil CO2 emissions showed a significantly positive correlation with soil fungal abundances, NAG activities, and ammonia nitrogen and nitrate nitrogen contents. Soil N2O emissions showed positive correlations with soil fungal, methanotroph, and nirK-type denitrifiers abundances, and DOC, ammonia nitrogen, and nitrate contents. These results demonstrate the importance of soil microbes, labile carbon, and nitrogen for regulating soil carbon and nitrogen emissions. The results of this study can assist simulating the effects of global climate change on carbon and nitrogen cycling in permafrost peatlands

Uncertainty-Aware Unlikelihood Learning Improves Generative Aspect Sentiment Quad Prediction

Recently, aspect sentiment quad prediction has received widespread attention in the field of aspect-based sentiment analysis. Existing studies extract quadruplets via pre-trained generative language models to paraphrase the original sentence into a templated target sequence. However, previous works only focus on what to generate but ignore what not to generate. We argue that considering the negative samples also leads to potential benefits. In this work, we propose a template-agnostic method to control the token-level generation, which boosts original learning and reduces mistakes simultaneously. Specifically, we introduce Monte Carlo dropout to understand the built-in uncertainty of pre-trained language models, acquiring the noises and errors. We further propose marginalized unlikelihood learning to suppress the uncertainty-aware mistake tokens. Finally, we introduce minimization entropy to balance the effects of marginalized unlikelihood learning. Extensive experiments on four public datasets demonstrate the effectiveness of our approach on various generation templates1

CRIT:Identifying RNA-binding protein regulator in circRNA life cycle via non-negative matrix factorization

Circular RNAs (circRNAs) are endogenous non-coding RNAs that regulate gene expression and participate in carcinogenesis. However, the RNA-binding proteins (RBPs) involved in circRNAs biogenesis and modulation remain largely unclear. We developed the circRNA regulator identification tool (CRIT), a non-negative matrix-factorization-based pipeline to identify regulating RBPs in cancers. CRIT uncovered 73 novel regulators across thousands of samples by effectively leveraging genomics data and functional annotations. We demonstrated that known RBPs involved in circRNA control are significantly enriched in these predictions. Analysis of circRNA-RBP interactions using two large cross-linking immunoprecipitation (CLIP) databases, we validated the consistency between CRIT prediction and the CLIP experiments. Furthermore, newly discovered RBPs are functionally connected with authentic circRNA regulators by various biological associations, such as physical interaction, similar binding motifs, common transcription factor modulation, and co-expression. When analyzing RNA sequencing (RNA-seq) datasets after short hairpin RNA (shRNA)/small interfering RNA (siRNA) knockdown, we found several novel RBPs that can affect global circRNA expression, which strengthens their role in the circRNA life cycle. The above evidence provided independent confirmation that CRIT is a useful tool to capture RBPs in circRNA processing. Finally, we show that authentic regulators are more likely the core splicing proteins and peripheral factors and usually harbor more alterations in the vast majority of cancers

Phased Treatment Strategies for Cerebral Ischemia Based on Glutamate Receptors

Extracellular glutamate accumulation following cerebral ischemia leads to overactivation of glutamate receptors, thereby resulting in intracellular Ca2+ overload and excitotoxic neuronal injury. Multiple attempts have been made to counteract such effects by reducing glutamate receptor function, but none have been successful. In this minireview, we present the available evidence regarding the role of all types of ionotropic and metabotropic glutamate receptors in cerebral ischemia and propose phased treatment strategies based on glutamate receptors in both the acute and post-acute phases of cerebral ischemia, which may help realize the clinical application of glutamate receptor antagonists

Dual antiplatelet therapy after percutaneous coronary intervention in patients at high bleeding risk: A systematic review and meta-analysis

Background: To date, it has not been ascertained whether shortening the duration of dual antiplatelet therapy (DAPT) can benefit high bleeding risk (HBR) patients. This systematic review and meta-analysis was performed to investigate the safety and efficacy of short (≤ 3 months) DAPT in HBR patients after percutaneous coronary intervention (PCI). Methods: The PubMed, Embase, and Clinical Trials databases were searched from inception until November 2021 to identify studies that evaluated the safety and efficacy of short DAPT in HBR patients implanted with new-generation drug-eluting stents (DES). Primary endpoints included major bleeding, definite or probable stent thrombosis (ST), and myocardial infarction (MI), while secondary endpoints included all-cause death and ischemic stroke. Based on the fixed and random effect model, the risk ratio (RR) and 95% confidence interval of each endpoint were measured. Results: Five observational studies and one randomized controlled trial were included, involving 15,432 HBR patients. Short DAPT for HBR patients undergoing PCI had a lower incidence of major bleeding in comparison with standard (> 3 months) DAPT (2.3% vs. 3.2%, RR 0.64 [0.44, 0.95], p = 0.03), while short DAPT was comparable to standard DAPT with regard to definite or probable ST (0.4% vs. 0.3%, RR 1.31 [0.77, 2.23], p = 0.32) and MI (2.4% vs. 2.0%, RR 1.17 [0.95, 1.45], p = 0.14). Conclusions: Among HBR patients implanted with new-generation DES, short DAPT was associated with reduced risk of major bleeding without significantly increasing the risk of definite or probable ST and MI in comparison with standard DAPT

The Atypical Effective Connectivity of Right Temporoparietal Junction in Autism Spectrum Disorder: A Multi-Site Study

Social function impairment is the core deficit of autism spectrum disorder (ASD). Although many studies have investigated ASD through a variety of neuroimaging tools, its brain mechanism of social function remains unclear due to its complex and heterogeneous symptoms. The present study aimed to use resting-state functional magnetic imaging data to explore effective connectivity between the right temporoparietal junction (RTPJ), one of the key brain regions associated with social impairment of individuals with ASD, and the whole brain to further deepen our understanding of the neuropathological mechanism of ASD. This study involved 1,454 participants from 23 sites from the Autism Brain Imaging Data Exchange (ABIDE) public dataset, which included 618 individuals with ASD and 836 with typical development (TD). First, a voxel-wise Granger causality analysis (GCA) was conducted with the RTPJ selected as the region of interest (ROI) to investigate the differences in effective connectivity between the ASD and TD groups in every site. Next, to obtain further accurate and representative results, an image-based meta-analysis was implemented to further analyze the GCA results of each site. Our results demonstrated abnormal causal connectivity between the RTPJ and the widely distributed brain regions and that the connectivity has been associated with social impairment in individuals with ASD. The current study could help to further elucidate the pathological mechanisms of ASD and provides a new perspective for future research

Phage vB_PaeS-PAJD-1 Rescues Murine Mastitis Infected With Multidrug-Resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative pathogen that causes a variety of infections in humans and animals. Due to the inappropriate use of antibiotics, multi-drug resistant (MDR) P. aeruginosa strains have emerged and are prevailing. In recent years, cow mastitis caused by MDR P. aeruginosa has attracted attention. In this study, a microbial community analysis revealed that P. aeruginosa could be a cause of pathogen-induced cow mastitis. Five MDR P. aeruginosa strains were isolated from milk diagnosed as mastitis positive. To seek an alternative antibacterial agent against MDR, P. aeruginosa, a lytic phage, designated vB_PaeS_PAJD-1 (PAJD-1), was isolated from dairy farm sewage. PAJD-1 was morphologically classified as Siphoviridae and was estimated to be about 57.9 kb. Phage PAJD-1 showed broad host ranges and a strong lytic ability. A one-step growth curve analysis showed a relatively short latency period (20 min) and a relatively high burst size (223 PFU per infected cell). Phage PAJD-1 remained stable over wide temperature and pH ranges. Intramammary-administered PAJD-1 reduced bacterial concentrations and repaired mammary glands in mice with mastitis induced by MDR P. aeruginosa. Furthermore, the cell wall hydrolase (termed endolysin) from phage PAJD-1 exhibited a strong bacteriolytic and a wide antibacterial spectrum against MDR P. aeruginosa. These findings present phage PAJD-1 as a candidate for phagotherapy against MDR P. aeruginosa infection

Climate warming accelerates temporal scaling of grassland soil microbial biodiversity.

Determining the temporal scaling of biodiversity, typically described as species-time relationships (STRs), in the face of global climate change is a central issue in ecology because it is fundamental to biodiversity preservation and ecosystem management. However, whether and how climate change affects microbial STRs remains unclear, mainly due to the scarcity of long-term experimental data. Here, we examine the STRs and phylogenetic-time relationships (PTRs) of soil bacteria and fungi in a long-term multifactorial global change experiment with warming (+3 °C), half precipitation (-50%), double precipitation (+100%) and clipping (annual plant biomass removal). Soil bacteria and fungi all exhibited strong STRs and PTRs across the 12 experimental conditions. Strikingly, warming accelerated the bacterial and fungal STR and PTR exponents (that is, the w values), yielding significantly (P < 0.001) higher temporal scaling rates. While the STRs and PTRs were significantly shifted by altered precipitation, clipping and their combinations, warming played the predominant role. In addition, comparison with the previous literature revealed that soil bacteria and fungi had considerably higher overall temporal scaling rates (w = 0.39-0.64) than those of plants and animals (w = 0.21-0.38). Our results on warming-enhanced temporal scaling of microbial biodiversity suggest that the strategies of soil biodiversity preservation and ecosystem management may need to be adjusted in a warmer world

Involvement of autophagy in mesaconitine-induced neurotoxicity in HT22 cells revealed through integrated transcriptomic, proteomic, and m6A epitranscriptomic profiling

Background: Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb Aconitum carmichaelii, is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms.Methods: HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both in vitro and in vivo, employing multi-omics techniques to explore the potential mechanisms of toxicity.Results: Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA.Conclusion: Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice

Demonstration of laser-produced neutron diagnostic by radiative capture gamma-rays

We report a new scenario of time-of-flight (TOF) technique in which fast neutrons and delayed gamma-ray signals were both recorded in a millisecond time window in harsh environments induced by high-intensity lasers. The delayed gamma signals, arriving far later than the original fast neutron and often being ignored previously, were identified to be the results of radiative captures of thermalized neutrons. The linear correlation between gamma photon number and the fast neutron yield shows that these delayed gamma events can be employed for neutron diagnosis. This method can reduce the detecting efficiency dropping problem caused by prompt high-flux gamma radiation, and provides a new way for neutron diagnosing in high-intensity laser-target interaction experiments