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Intraventricular haemorrhage (IVH) is a severe and acute type of stroke with a complex pathophysiology and is a therapeutic challenge. This case report described a man in his early 50’s diagnosed with IVH by computed tomography (CT). Although bilateral extraventricular drainage (EVD) was undertaken, a postoperative CT scan showed that while the left catheter was correctly positioned, the right catheter had been wrongly inserted into the cisterna ambiens. The procedure was equivalent to simultaneous EVD combined with cisternostomy. As a consequence, the haematoma was rapidly removed, the risk of infection and long-term hydrocephalus was reduced, and prognosis was improved. Large case-control studies or prospective studies are needed to evaluate the safety and effectiveness of this treatment modality.

As the main friction pair of engine, the friction loss of piston-cylinder liner assembly in the working process has become the main reason of engine friction power consumption. Many species in the biological world have formed non-smooth forms of resistance reduction after thousands of years of survival and evolution. Many people have applied this non-smooth shape of drag reduction on organisms to the surface of friction pairs in construction machinery. Based on LX108 engine, the wear and erosion resistance of Scapharca subcrenata surface is applied to the piston skirt, which is the main friction pair in the engine. Nine test schemes were designed according to orthogonal test. This design selects three factors, namely, groove distribution type, groove depth and width, groove spacing, and each factor includes three levels. The macroscopic fluid lubrication state of the whole piston skirt with bionic shape is studied. Through the change of oil film thickness caused by thermal-mechanical coupling deformation of skirt, combined with the average Reynolds equation, the hydrodynamic pressure of lubricating oil, shear stress, and skirt friction force are obtained to verify the contribution of bionic shape to piston drag reduction, wear reduction, wetting increase, and friction power consumption. The simulation and test results show that the lubrication of all parts of the bionic groove piston skirt is better than that of the standard piston; When the depth and width of groove is 0.8 mm and the spacing is 10°, the thicker the oil film thickness of skirt is; The bionic piston whose oil film bearing area is 74%–87% of the standard piston has the smallest normal pressure and friction; When the upper end of the skirt is arranged with groove shape and the lower end is arranged with narrow groove shape between wide grooves, the lubrication effect is better.

Vehicle trajectory prediction is a key technology in autonomous driving, one of the aims of which is to ensure the safety of vehicle travelling and lane changing. Especially in complex traffic scenarios, it is critical to accurately predict the vehicle trajectory so that the automated driving system can make appropriate response actions to help the vehicle driver avoid accidents to the greatest extent possible. Some studies on vehicle trajectory prediction have used recurrent networks (LSTMs) to extract temporal correlations and additional convolutional neural networks (CNNs) to capture spatial correlations. This hybrid model can be added more operations, so we propose a new CNN-LSTM hybrid model containing multi-module, interaction regions and spatial-temporal attention mechanisms (IA-CSTM). In this paper, the traffic scene is divided into multiple interaction regions, and vehicles in different regions have different impacts on the predicted vehicles. The model has multiple modules that deal with vehicle information in different interaction regions. The model will cross-fuse vehicle information in important interaction regions to enhance the model’s perception of vehicle information. Multiple modules are linked through a spatial-temporal attention mechanism and capture the relevance of the vehicle in the interaction region to predicted vehicle.

(1) Background: Excessive nitrogen (N) fertilizer application in tea plantations leads to challenges such as soil acidification and nitrogen loss, impending the sustainable development of the plantation system. Yet, there is a lack of research on blended fertilization strategies, and limited data regarding N loss when substituting with organic fertilizer. (2) Methods: A year-long field monitoring experiment was conducted to evaluate the effects of substituting compound fertilizer with organic fertilizer, specifically with respect to runoff N loss and uptake of chemical fertilizer N by tea trees. (3) Results: The annual runoff N loss ranged from 0.16 to 0.57 kg·hm−2 and accounted for a mere 0.22–0.48% of N from fertilizer applications. Substitution with organic fertilizer reduced runoff N loss by 21–53% and improved the tea tree utilization efficiency of chemical fertilizer N from 16% to 27%. A 50% organic fertilizer substitution (based on the amount of N) promoted a net soil N mineralization rate, creating an ammonium-rich environment favored by tea trees. (4) Conclusions: The positive effects of partially substituting N fertilizer with organic fertilizer in tea plantation systems on both N utilization efficiency and N loss were confirmed. If conditions permit, the study team would aim to expand the temporal scope of the study, and to investigate the impact of organic fertilizer substitution on N loss under various precipitation intensities.

Off-treatment HBsAg reversion occurs in a considerable number of chronic hepatitis B(CHB) patients after IFN(interferon)-induced HBsAg clearance. HBV vaccination protects the general population against HBV infection. However, it remains unclear whether HBV vaccination could prevent off-treatment HBsAg reversion in CHB patients with HBsAg clearance. CHB patients (n = 199) with HBsAg clearance were included in the current study, comprising spontaneous HBsAg clearance group (n = 51), NA (nucleoside/nucleotide analogues)-induced group (n = 36) and IFN-induced group (n = 112). Log-rank test was performed to compare the cumulative incidences of HBsAg reversion between groups. Cox regression model was used to identify the factors associated with off-treatment HBsAg reversion. The 5-year cumulative incidence of HBsAg reversion in IFN-induced group was significantly higher than that in NA-induced group or spontaneous group (27.6% vs. 3.3% vs. 8.1%, both p 100mIU/ml) was significantly lower than that in those with weak responses to HBV vaccination (HBsAb level ≤100mIU/ml) or without HBV vaccination in IFN-induced group (7.7% vs. 58.5% vs. 31.9%, both p

Despite significant advances of the bovine epigenome investigation, new evidence for the epigenetic basis of fetal cartilage development remains lacking. In this study, the chondrocytes were isolated from long bone tissues of bovine fetuses at 90 days. The Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) were used to characterize gene expression and chromatin accessibility profile in bovine chondrocytes. A total of 9686 open chromatin regions in bovine fetal chondrocytes were identified and 45% of the peaks were enriched in the promoter regions. Then, all peaks were annotated to the nearest gene for Gene Ontology (GO) and Kyoto Encylopaedia of Genes and Genomes (KEGG) analysis. Growth and development-related processes such as amide biosynthesis process (GO: 0043604) and translation regulation (GO: 006417) were enriched in the GO analysis. The KEGG analysis enriched endoplasmic reticulum protein processing signal pathway, TGF-β signaling pathway and cell cycle pathway, which are closely related to protein synthesis and processing during cell proliferation. Active transcription factors (TFs) were enriched by ATAC-seq, and were fully verified with gene expression levels obtained by RNA-seq. Among the top50 TFs from footprint analysis, known or potential cartilage development-related transcription factors FOS, FOSL2 and NFY were found. Overall, our data provide a theoretical basis for further determining the regulatory mechanism of cartilage development in bovine.

Background & AimsDrug-induced liver injury (DILI) is one of the leading causes of liver failure with some of the patients progressed to chronic DILI. The mechanisms underlying the severity and chronicity of DILI are poorly elucidated and the biomarkers are limited. Metabolites and gut microbiota played a crucial role in the development of various liver diseases. Herein, a systematic analysis of serum metabolites and gut microbiota was performed in DILI patients, aiming to identify metabolites correlated with the progression and clinical prognosis of DILI.MethodsVarious serum metabolites were quantitated using a metabolite array technology in this prospective study. Gut microbiome compositions and the expression profiles of liver genes were determined in patients with DILI and healthy controls.ResultsMetabolomic analysis revealed that bile acids (BAs) and polyunsaturated fatty acids (PUFAs) were closely related to DILI severity and chronicity respectively. The ratios of serum primary/secondary BAs and omega-6/omega-3 PUFAs were elevated in DILI patients. A model established by adrenic acid (AdA) and aspartic acid (Asp) exerts good performance for predicting the chronicity of DLIL. Hepatic transcriptome revealed enhanced expression of PUFA peroxidation and supressed expression of BA synthesis related genes in DILI patients. In addition, Lactic acid bacteria and BA converting bacteria were increased in gut of DILI patients. Besides, elevated serum malondialdehyde (MDA) and fibroblast growth factor 19 (FGF19) was observed in DILI patients.ConclusionBAs and PUFAs could be potent markers for the severity and chronicity of DILI respectively. The panel of AdA and Asp could be ideal predictive model for the risk of chronicity at the acute stage of DILI. Gut microbiota might act as a negative feedback mechanism to maintain the homeostasis of BAs and PUFAs via FGF19 signalling and PUFA saturation, respectively. Our study revealed novel biomarkers for severe and chronic DILI and provided new therapeutic targets for DILI.

Objective: To evaluate the efficacy and safety of tirofiban for patients with acute ischemic stroke (AIS), especially posterior circulation stroke (PCS).Methods: We enrolled consecutive patients with AIS who suffered large artery occlusion (LAO) and underwent mechanical thrombectomy (MT) between January 2016 and May 2020. Patients were divided into two groups according to whether tirofiban was used during MT. The primary efficacy outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 3 months. The safety outcomes were the rate of mortality at 3 months and the presence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH). Cohorts were balanced using 1:1 propensity score matching (PSM). Subgroup analysis was further performed to compare the efficacy and safety of tirofiban between the anterior circulation stroke (ACS) and PCS groups.Results: A total of 292 patients were eligible for this study and divided into the tirofiban group (n = 51) and the no-tirofiban group (n = 241). In the propensity-score-matched cohort, the tirofiban group had a higher rate of favorable outcomes than the no-tirofiban group (49.0 vs. 25.5%, p = 0.014), and the mortality at 3 months showed a greater downward trend in the tirofiban group than the no-tirofiban group (15.6 vs. 33.3% p = 0.064). The risk of sICH and ICH was the same between the tirofiban and control groups (17.6 vs. 27.4% p = 0.236, 31.3 vs. 45.1% p = 0.154, respectively). Tirofiban use was predictive of favorable outcomes [adjusted odds ratio (aOR) = 2.87, 95% confidence interval (CI) 1.52–6.44, p = 0.043] after multiple logistic regression analysis. Subgroup analysis revealed that tirofiban use was significantly associated with favorable outcomes in ACS (aOR = 3.66, 95% CI 1.24–5.22, p = 0.019) but not in PCS (aOR = 1.12, 95% CI 0.47–7.52, p = 0.570).Conclusion: We demonstrated that tirofiban may be associated with improving favorable outcome for the AIS patients who underwent MT, without increasing ICH or sICH. Furthermore, our results indicated that for PCS patients tirofiban may not be associated with favorable outcome, and more comprehensive randomized controlled trials are needed to confirm this finding.

Tirofiban has recently shown encouraging efficacy and safety among acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT). However, the benefits of tirofiban varied among studies depending on the patient’s condition, which was often not well analyzed. This study aimed to identify the characteristics of patients who may obtain the largest benefits from tirofiban. The efficacy endpoint was a favorable outcome defined as a modified Rankin Scale (mRS) score of 0~2 at 90 days. The safety endpoints were intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Adjusted logistic regression analysis and subgroup analyses were utilized to investigate the factors associated with tirofiban and the outcome. All of 285 patients fit the inclusion criteria. Tirofiban was associated with a higher rate of favorable outcome (aOR 2.033, 95% CI, 1.002~4.123, p = 0.043) but not with an increased risk of ICH, sICH or mortality (p > 0.05). Moreover, subgroup analyses revealed that tirofiban was associated with favorable outcomes in patients with NIHSS > 14 (aOR 2.778, 95% CI 1.056~7.356, p = 0.038) but not in patients with NIHSS ≤ 14 (aOR 1.719, 95% CI 0.646~4.578, p = 0.278). No significant heterogeneity was found in the effect of tirofiban across the subgroups of age, sex, ASPECTS, time from onset to puncture, use of t-PA or stroke etiology (p for interaction > 0.05). The administration of tirofiban was associated with favorable outcomes in severe ischemic stroke patients, and further studies are needed to confirm this finding.

Aneurysmal subarachnoid hemorrhage (aSAH) is an important type of stroke with the highest rates of mortality and disability. Recent evidence indicates that neuroinflammation plays a critical role in both early brain injury and delayed neural deterioration after aSAH, contributing to unfavorable outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a peripheral biomarker that conveys information about the inflammatory burden in terms of both innate and adaptive immunity. This review summarizes relevant studies that associate the NLR with aSAH to evaluate whether the NLR can predict outcomes and serve as an effective biomarker for clinical management. We found that increased NLR is valuable in predicting the clinical outcome of aSAH patients and is related to the risk of complications such as delayed cerebral ischemia (DCI) or rebleeding. Combined with other indicators, the NLR provides improved accuracy for predicting prognosis to stratify patients into different risk categories. The underlying pathophysiology is highlighted to identify new potential targets for neuroprotection and to develop novel therapeutic strategies.

Abstract Background Neuroinflammation is closely associated with functional outcome in subarachnoid hemorrhage (SAH) patients. Our recent study demonstrated that fluoxetine inhibited NLRP3 inflammasome activation and attenuated necrotic cell death in early brain injury after SAH, while the effects and potential mechanisms of fluoxetine on neuroinflammation after SAH have not been well-studied yet. Methods One hundred and fifty-three male SD rats were subjected to the endovascular perforation model of SAH. Fluoxetine (10 mg/kg) was administered intravenously at 6 h after SAH induction. TAK-242 (1.5 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h after SAH. SAH grade, neurological scores, brain water content, Evans blue extravasation, immunofluorescence/TUNEL staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were performed. Results Fluoxetine administration attenuated BBB disruption, brain edema, and improved neurological function after SAH. In addition, fluoxetine alleviated the number of Iba-1-positive microglia/macrophages, neutrophil infiltration, and cell death. Moreover, fluoxetine reduced the levels of pro-inflammatory cytokines, downregulated the expression of TLR4 and MyD88, and promoted the nuclear translocation of NF-κB p65, which were also found in rats with TAK-242 administration. Combined administration of fluoxetine and TAK-242 did not enhance the neuroprotective effects of fluoxetine. Conclusion Fluoxetine attenuated neuroinflammation and improved neurological function in SAH rats. The potential mechanisms involved, at least in part, TLR4/MyD88/NF-κB signaling pathway.

Abstract Background The size of the protein sequence database has been exponentially increasing due to advances in genome sequencing. However, experimentally characterized proteins only constitute a small portion of the database, such that the majority of sequences have been annotated by computational approaches. Current automatic annotation pipelines inevitably introduce errors, making the annotations unreliable. Instead of such error-prone automatic annotations, functional interpretation should rely on annotations of ‘reference proteins’ that have been experimentally characterized or manually curated. Results The Seq2Ref server uses BLAST to detect proteins homologous to a query sequence and identifies the reference proteins among them. Seq2Ref then reports publications with experimental characterizations of the identified reference proteins that might be relevant to the query. Furthermore, a plurality-based rating system is developed to evaluate the homologous relationships and rank the reference proteins by their relevance to the query. Conclusions The reference proteins detected by our server will lend insight into proteins of unknown function and provide extensive information to develop in-depth understanding of uncharacterized proteins. Seq2Ref is available at: http://prodata.swmed.edu/seq2ref.

DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.

Abstract Background Computational sequence analysis, that is, prediction of local sequence properties, homologs, spatial structure and function from the sequence of a protein, offers an efficient way to obtain needed information about proteins under study. Since reliable prediction is usually based on the consensus of many computer programs, meta-severs have been developed to fit such needs. Most meta-servers focus on one aspect of sequence analysis, while others incorporate more information, such as PredictProtein for local sequence feature predictions, SMART for domain architecture and sequence motif annotation, and GeneSilico for secondary and spatial structure prediction. However, as predictions of local sequence properties, three-dimensional structure and function are usually intertwined, it is beneficial to address them together. Results We developed a MEta-Server for protein Sequence Analysis (MESSA) to facilitate comprehensive protein sequence analysis and gather structural and functional predictions for a protein of interest. For an input sequence, the server exploits a number of select tools to predict local sequence properties, such as secondary structure, structurally disordered regions, coiled coils, signal peptides and transmembrane helices; detect homologous proteins and assign the query to a protein family; identify three-dimensional structure templates and generate structure models; and provide predictive statements about the protein's function, including functional annotations, Gene Ontology terms, enzyme classification and possible functionally associated proteins. We tested MESSA on the proteome of Candidatus Liberibacter asiaticus. Manual curation shows that three-dimensional structure models generated by MESSA covered around 75% of all the residues in this proteome and the function of 80% of all proteins could be predicted. Availability MESSA is free for non-commercial use at http://prodata.swmed.edu/MESSA/

This study addresses the problem that the traditional method is not effective in improving the adsorption performance of vacuum suckers. From the perspective of bionics, the adsorption performance of bionic suckers based on the excellent adsorption of the abalone abdominal foot was studied. A bionic sucker was designed by extracting the sealing ring structure of the abdominal foot tentacle. The bionic sucker was subjected to tensile experiments using an orthogonal experimental design, and the adsorption of the bionic sucker was simulated and analyzed to explore its adsorption mechanism. The results show that the primary and secondary factors affecting the adsorption of the sucker are the number of sealing rings, the width of sealing rings and the spacing of sealing rings. At 60% vacuum, the bionic sucker with two sealing rings, a 1.5 mm sealing ring width and 3 mm sealing ring spacing has the largest adsorption force, and its maximum adsorption force is 15.8% higher than that of the standard sucker. This study shows that the bionic sucker design can effectively improve the adsorption performance of the sucker. The bionic sucker had a different stress distribution on the sucker bottom, which resulted in greater Mises stress in the sealing ring and the surrounding area, while the Mises stress in the central area of the sucker was smaller. [ABSTRACT FROM AUTHOR]

A propeptide is removed from a precursor protein to generate its active or mature form. Propeptides play essential roles in protein folding, transportation, and activation and are present in about 2.3% of reviewed proteins in the UniProt database. They are often found in secreted or membrane‐bound proteins including proteolytic enzymes, hormones, and toxins. We identified a variety of globular and nonglobular Pfam domains in protein sequences designated as propeptides, some of which form intramolecular interactions with other domains in the mature proteins. Propeptide‐containing enzymes mostly function as proteases, as they are depleted in other enzyme classes such as hydrolases acting on DNA and RNA, isomerases, and lyases. We applied AlphaFold to generate structural models for over 7000 proteins with propeptides having no less than 20 residues. Analysis of residue contacts in these models revealed conformational changes for over 300 proteins before and after the cleavage of the propeptide. Examples of conformation change occur in several classes of proteolytic enzymes in the families of subtilisins, trypsins, aspartyl proteases, and thermolysin‐like metalloproteases. In most of the observed cases, cleavage of the propeptide releases the constraints imposed by the covalent bond between the propeptide and the mature protein, and cleavage enables stronger interactions between the propeptide and the mature protein. These findings suggest that post‐cleavage propeptides could play critical roles in regulating the activity of mature proteins. [ABSTRACT FROM AUTHOR]

A variety of bionic vacuum suckers with papillae structures of different parameters were developed to improve the attachment performance of vacuum suckers. The oral sucker of the suckermouth catfish served as the bionic prototype and bionic suckers were made by taking the diameter of papillae, the number of single rows of papillae, the center distance between adjacent rows of papillae, and the distance between the outermost row of papillae and the edge as influencing factors. The single-factor tests and response surface tests were carried out respectively with the growth rates of vertical and horizontal attachment forces as the response values. Twenty-five groups of bionic suckers and one group of standard suckers were fabricated and tested for attachment forces. The experimental results revealed that the bionic suckers had higher vertical and horizontal attachment forces than standard suckers and that their maximum growth rates for these forces were 5.16% and 59.87%, respectively. This suggested that the bionic suckers had better attachment performance. The significant orders of the factors affecting response values were established and their interaction was also analyzed. Besides, the optimal parameter combination of papillae structures of the bionic suckers with optimal vertical and horizontal attachment properties was obtained, respectively. Finally, the influence mechanism of papillae structures on the attachment properties of bionic suckers was analyzed. The studies can serve as a guide for the application of bionic suckers in agricultural production areas such as fruit picking and handling, and the improvement of attachment performance of associated machinery. [ABSTRACT FROM AUTHOR]

The Karner blue butterfly, Plebejus (Lycaeides) samuelis, is an endangered North American climate change‐vulnerable species that has undergone substantial historical habitat loss and population decline. To better understand the species' genetic status and support Karner blue conservation, we sampled 116 individuals from 22 localities across the species' geographical range in Wisconsin (WI), Michigan (MI), Indiana (IN), and New York (NY). Using genomic analysis, we found that these samples were divided into three major geographic groups, NY, WI, and MI‐IN, with populations in WI and MI‐IN each further divided into three subgroups. A high level of inbreeding was revealed by inbreeding coefficients above 10% in almost all populations in our study. However, strong correlation between FST and geographical distance suggested that genetic divergence between populations increases with distance, such that introducing individuals from more distant populations may be a useful strategy for increasing population‐level diversity and preserving the species. We also found that Karner blue populations had lower genetic diversity than closely related species and had more alleles that were present only at low frequencies (<5%) in other species. Some of these alleles may negatively impact individual fitness and may have become prevalent in Karner blue populations due to inbreeding. Finally, analysis of these possibly deleterious alleles in the context of predicted three‐dimensional structures of proteins revealed potential molecular mechanisms behind population declines, providing insights for conservation. This rich new range‐wide understanding of the species' population genomic structure can contextualize past extirpations and help conserve and even enhance Karner blue genetic diversity. [ABSTRACT FROM AUTHOR]