We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment ...indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets,
N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.
FMRP is a selective mRNA-binding protein that regulates protein synthesis at synapses, and its loss may lead to the impairment of trace fear memory. Previously, we found that FMRP levels in the ...hippocampus of rats with post-traumatic stress disorder (PTSD) were decreased. However, the mechanism underlying these changes remains unclear.
Forty-eight male Sprague-Dawley rats were randomly divided into four groups. The experimental groups were treated with the single-prolonged stress (SPS) procedure and injected with a lentivirus-mediated inhibitor of miR-142-5p. Behavior test as well as morphology and molecular biology experiments were performed to detect the effect of miR-142 downregulation on PTSD, which was further verified by in vitro experiments.
We found that silence of miRNA-142 (miR-142), an upstream regulator of FMRP, could alleviate PTSD-like behaviors of rats exposed to the SPS paradigm. MiR-142 silence not only decreased the levels of proinflammatory mediators, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, but also increased the expressive levels of synaptic proteins including PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We further detected that miR-142 silence also downregulated the transportation of nuclear factor kappa-B (NF-κB) into the nuclei of neurons and might further affect the morphology of neurons.
The results revealed miR-142 downregulation could alleviate PTSD-like behaviors through attenuating neuroinflammation in the hippocampus of SPS rats by binding to FMRP.
Unmanned ship navigates on the water in an autonomous or semiautonomous way, which can be widely used in maritime transportation, intelligence collection, maritime training and testing, ...reconnaissance, and evidence collection. In this paper, we use deep reinforcement learning to solve the optimization problem in the path planning and management of unmanned ships. Specifically, we take the waiting time (phase and duration) at the corner of the path as the optimization goal to minimize the total travel time of unmanned ships passing through the path. We propose a new reward function, which considers the environment and control delay of unmanned ships at the same time, which can reduce the coordination time between unmanned ships at the same time. In the simulation experiment, through the quantitative and qualitative results of deep reinforcement learning of unmanned ship navigation and path angle waiting, the effectiveness of our solution is verified.
Nanofluidics derived from low‐dimensional nanosheets and protein nanochannels are crucial for advanced catalysis, sensing, and separation. However, polymer nanofluidics is halted by complicated ...preparation and miniaturized sizes. This work reports the bottom‐up synthesis of modular nanofluidics by confined growth of ultrathin metal–organic frameworks (MOFs) in a polymer membrane consisting of zwitterionic dopamine nanoparticles (ZNPs). The confined growth of the MOFs on the ZNPs reduces the chain entanglement between the ZNPs, leading to stiff interfacial channels enhancing the nanofluidic transport of water molecules through the membrane. As such, the water permeability and solute selectivity of MOF@ZNPM are one magnitude improved, leading to a record‐high performance among all polymer nanofiltration membranes. Both the experimental work and the molecular dynamics simulations confirm that the water transport is shifted from high‐friction‐resistance conventional viscous flow to ultrafast nanofluidic flow as a result of rigid and continuous nanochannels in MOF@ZNPM.
A rigid‐scaffold‐reinforced polymeric nanoparticles’ interfacial channel strategy is proposed for fabricating nanofluidic membranes that exhibit water permeance and dye/salt selectivity that are 1–2 orders of magnitude higher than conventional polymeric membranes. The unprecedented separation performance is due to the paradigm shift of water transport from conventional viscous flow to ultrafast nanofluidic flow in the membrane nanofluidics.
The role of autophagy in the cardioprotection conferred by ischemic preconditioning (IPC) has been well described. This study aimed to investigate the changes in autophagy levels during the ...cardioprotective effects initiated by exercise preconditioning (EP).Rats were randomly divided into 4 groups: group C (control), group EP, group EE (exhaustive exercise), and group EP + EE (EP pretreatment at 0.5 hours before EE). The EP protocol included 4 periods of 10 minutes of treadmill running each at 30 m/minute with intervening 10 minute periods of rest. Hematoxylin-basic fuchsin-picric acid (HBFP) staining and plasma levels of cardiac troponin I (cTnI) were used to evaluate the ischemia-hypoxia injury in rat myocardium. Alteration levels in several autophagy proteins in the left ventricular myocardium were analyzed by Western blot. The phasic alterations of autophagy levels during EP-initiated cardioprotective phase were also examined.Compared with group C, the ischemia-hypoxia positive areas and IOD value in HBFP-staining and cTnI plasma levels increased significantly in group EE. Compared with group EE, the ischemia-hypoxia injury was markedly attenuated in group EP + EE. Compared with group C, the LC3-II/LC3-I ratio, a marker of autophagosome formation, was reduced in group EE, but the LC3-II/LC3-I ratio remained unaltered in group EP + EE. Furthermore, the LC3-II/LC3-I ratio increased significantly at 2 hours during the cardioprotective phase after EP.These results suggest that the activated autophagy level during the EP-initiated cardioprotective phase may be partly involved in the cardioprotective effects by maintaining a normal autophagy basal level during the subsequent exhaustive exercise in rat myocardium.
Pyogenic liver abscess (PLA) is a severe condition that significantly increases the risk of sepsis. However, there is a notable dearth of research regarding the prediction of sepsis in PLA patients. ...The objective of this study was to develop and validate a prognostic nomogram for predicting sepsis in PLA patients. A total of 206 PLA patients were enrolled in our study, out of which 60 individuals (29.1%) met the Sepsis-3 criteria. Independent risk factors for sepsis were identified through univariate and multivariate logistic regression analyses. Subsequently, a nomogram was developed based on age, positive blood culture, procalcitonin, alanine aminotransferase, blood urea nitrogen, and D-dimer. The nomogram demonstrated excellent calibration and discrimination, as evidenced by the area under the receiver operating characteristic curve (AUC) values of 0.946 (95% confidence interval CI, 0.912-0.979) and 0.980 (95%CI 0.951-1.000) in the derivation and validation cohorts, respectively. Furthermore, decision-curve analysis confirmed the clinical utility of the nomogram. This study provides valuable insights for the prevention of sepsis in PLA patients and underscores the potential application of the prognostic nomogram in clinical practice.
Fragile X-related protein 1 (FXR1) is a member of the fragile X family of RNA-binding proteins, which regulates a number of neurological and neuropsychiatric disorders such as fragile X syndrome, and ...is expected as a novel therapeutic target for some psychiatric diseases. However, it is unknown how FXR1 changes and functions in post-traumatic stress disorder (PTSD), a common mental disorder related to trauma and stressor. In this study, we characterized the expression pattern of FXR1 in the pathophysiological process of PTSD and further investigated the possible mechanism underlying these changes by finding an upstream regulator, namely miRNA-132 (miR-132). Furthermore, we verified whether miR-132 silence had an effect on the PTSD-like behaviors of single prolonged stress (SPS) rats through open field test, forced swimming test, and water maze test. At last, we examined the expression levels of PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We showed that the levels of FXR1 and fragile X mental retardation protein (FMRP), an autosomal homolog of FXR1, were decreased in the hippocampus of PTSD rats, but the levels of PSD95 and synapsin I were increased, which could be reversed by downregulation of miR-132. The results revealed that miR-132 could modulate PTSD-like behaviors in rats following SPS through regulating FXR1 and FMRP.
•MiR-142 levels were significantly increased in the amygdala of rats subjected to SPS.•Npas4 was identified as a direct target of miR-142.•Activation of miR-142 reduced the expression of Npas4 and ...BDNF.•Administration of LV-anti-miR-142 into amygdalae abolished the behavioral responses caused by SPS.
Posttraumatic stress disorder (PTSD) is a prevalent mental disorder that is classified as a trauma- and stressor-related disorder. While numerous epigenetic factors are related to the risk for PTSD, the precise mechanisms underlying this disorder remain unclear. However, accumulating evidence has demonstrated that dysregulation of microRNAs is involved in stress-related psychiatric disorders, resulting in anxiety-like behavior, memory-related deficits and aberrant neuronal plasticity. Here, rats exposed to single prolonged stress showed increased microRNA-142-5p levels in the amygdala and a concurrent reduction in the levels of its predicted target Npas4, an activity-regulated transcription factor, which was implicated in stress-related psychopathologies. In addition, the inhibition of microRNA-142 following exposure to single prolonged stress exhibited decreased anxiety-like behaviors and memory deficits, as well as increased expression of Npas4 and BDNF. Furthermore, a dual-luciferase reporter assay indicated that Npas4 was a direct downstream target of miR-142. Taken together, these data suggest that miR-142 may play a key role in the pathogenesis of stress-related psychiatric disorders.
Objective
People can be categorized into one of four meaning‐in‐life profiles: High Presence High Search (HPHS), High Presence Low Search (HPLS), Low Presence High Search (LPHS), and Low Presence Low ...Search (LPLS).The main goal of this study is to provide a theoretical explanation for why Chinese people with different meaning‐in‐life profiles have different mental health levels than Western people, based on their emotional‐cognitive‐processing ability.
Method
We adopted eye‐movement analysis and recognition‐judgment experimental paradigm concerning absolute‐recognition judgment and relative‐recognition judgment in our study. Moreover, we applied a multifactor and multilevel mixed‐experimental design. We selected 118 participants for the experiments from the 788 Chinese college students who responded.
Results
Our results showed that HPHS individuals preferred positive‐emotion pictures, LPLS individuals preferred negative‐emotion pictures, HPLS individuals preferred positive‐ and neutral‐emotion pictures, and LPHS individuals preferred neutral‐emotion pictures. Moreover, HPHS individuals were better at accurately processing facial expression from pictures, while LPLS individuals lacked such ability. The fine‐processing ability of HPLS and LPHS individuals was lower than that of HPHS yet higher than that of LPLS individuals. Moreover, the features of HPLS individuals were closer to HPHS, while those of LPHS individuals were closer to LPLS.
Conclusions
Our findings support the hypothesis that meaning‐in‐life profiles have different immediate processing abilities and preferences regarding facial expression recognition and different emotional‐cognitive‐processing ability.
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