Vasogenic brain edema after subarachnoid hemorrhage (SAH) is an independent risk factor for death and poor prognosis. Disruption of the blood-brain barrier (BBB) is the main cause of vasogenic brain ...edema induced by SAH. Oleanolic acid (OA) is a natural pentacyclic triterpenoid with various biological functions. Previous studies have shown that prophylactic administration of OA could prevent the BBB disruption in autoimmune encephalomyelitis mice. In this context, we speculate that OA may play a neuroprotective role by protecting the integrity of the BBB and reducing vasogenic cerebral edema after SAH. To validate this hypothesis, a SAH model was established on Sprague Dawley rats using a standard intravascular puncture model. The effects of OA on various physiological indexes were observed, including SAH grades, mortality, neurological function score, brain edema and BBB permeability. Related proteins of the brain endothelial cell junction complex were also detected, including tight junctions (TJs) and adherent junctions (AJs). Results showed that OA significantly reduced the permeability of BBB and relieved brain edema by increasing protein expression of TJs and AJs, and decreased the SAH grades by increasing the protein expression of heme oxygenase-1 (HO-1) in SAH rats. Additionally, we found OA could inhibit up-regulation of VEGF and the phosphorylation of p38 mitogen-activated protein kinase (MAPK), and suppress p38MAPK/VEGF/Src signaling pathway which involved in BBB disruption following SAH. From the experimental results, we speculate that OA effectively alleviated SAH-induced vasogenic edema by targeting p38 MAPK/VEGF/Src axis.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and CD4+ T lymphocytes can inhibit hepatocarcinogenesis and mediate tumor regression. However, few ...studies have focused on the prognostic power of CD4+ Tconv-related lncRNAs in HCC patients.
We obtained data from TCGA and GEO databases and identified CD4+Tconv-related lncRNAs in HCC. The risk score was constructed using lasso regression and the model was validated using two validation cohorts. The RS was also assessed in different clinical subgroups, and a nomogram was established to further predict the patients' outcomes. Furthermore, we estimated the immune cell infiltration and cancer-associated fibroblasts (CAFs) through TIMER databases and assessed the role of RS in immune checkpoint inhibitors response.
We constructed a CD4+ Tconv-related lncRNAs risk score, including six lncRNAs (AC012073.1, AL031985.3, LINC01060, MKLN1-AS, MSC-AS1, and TMCC1-AS1), and the RS had good predictive ability in validation cohorts and most clinical subgroups. The RS and the T stage were included in the nomogram with optimum prediction and the model had comparable OS prediction power compared to the AJCC. Patients in the high-risk group had a poor immune response phenotype, with high infiltrations of macrophages, CAFs, and low infiltrations of NK cells. Immunotherapy and chemotherapy response analysis indicated that low-risk group patients had good reactions to immune checkpoint inhibitors.
We constructed and validated a novel CD4+ Tconv-related lncRNAs RS, with the potential predictive value of HCC patients' survival and immunotherapy response.
In this work, the relationship between rolling contact fatigue (RCF) failure and the microstructure of D2 wheel steel was studied using a GPM-30 fatigue tester under oil lubrication conditions. The ...microstructural evolution during the RCF process can be divided into three stages: In the first stage, the misorientation of the proeutectoid ferrite is 2°–10°, the ferrite phase in pearlite is less than 2°, and the dislocation density is low. In the second stage, with the increase in cycles, the misorientation of the proeutectoid ferrite increases to more than 10°, and the ferrite phase in pearlite increases to 2°–10°. In the third stage, the misorientation of the ferrite phase in pearlite increases to more than 10°, the ferrite phase is divided into fine grains, and the dislocation density is high. RCF cracks are formed in the third stage. Crack initiation is ascribed to the refinement of the surface ferrite phase and proeutectoid ferrite and the increase in dislocation density. RCF cracks are initiated and propagate primarily at the interface of pearlite/proeutectoid ferrite and in proeutectoid ferrite.
Debugging a genome sequence is imperative for successfully building a synthetic genome. As part of the effort to build a designer eukaryotic genome, yeast synthetic chromosome X (synX), designed as ...707,459 base pairs, was synthesized chemically. SynX exhibited good fitness under a wide variety of conditions. A highly efficient mapping strategy called pooled PCRTag mapping (PoPM), which can be generalized to any watermarked synthetic chromosome, was developed to identify genetic alterations that affect cell fitness ("bugs"). A series of bugs were corrected that included a large region bearing complex amplifications, a growth defect mapping to a recoded sequence in
, and a loxPsym site affecting promoter function of
PoPM is a powerful tool for synthetic yeast genome debugging and an efficient strategy for phenotype-genotype mapping.
A mesoporous ZnS shell is in situgrown on a CdS core through a one-pot surfactant-free hydrothermal route. Due to the mesoporous ZnS shell and the unique spatial distribution of the photoexcited ...charge carriers in the CdS-ZnS core-shell particles, the hydrogen evolution rate over CdS-ZnS is 169 and 56 times higher than that of ZnS and CdS under visible light, respectively. Moreover, the core-shell particles show excellent photocatalytic stability over 60 h.
The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) remains poor even after radical pancreaticoduodenectomy (PD). The study aimed to develop and validate a novel preoperative ...prognostic model to accurately predict the long-term survival of patients with PDAC.
Patients with PDAC of pancreatic head from Chinese PLA General Hospital were included. The preoperative PDAC model with contour plots was developed using a non-linear model in the training cohort and then tested in the validation cohort.
Of 421 patients who met the inclusion criteria, 280 were in the training cohort and 141 in the validation cohort. Contour plots for preoperative PDAC model were established to visually predict the survival probabilities of these patients, based on preoperative carbohydrate antigen 19-9, preoperative fibrinogen to albumin ratio and pain symptoms. This model stratified patients into low- and high-risk groups with distinctly different long-term survival in the training cohort median overall survival (OS) 32.1 vs. 17.5 months; median recurrence-free survival (RFS) 19.3 vs. 10.0 months, both P < 0.001 and the validation cohort (median OS 28.3 vs. 19.0 months; median RFS 17.5 vs. 11.2 months, both P < 0.001). Time-dependent receiver operating characteristic and decision curve analyses revealed that the model provided higher diagnostic accuracy and superior net benefit compared to other staging systems.
This study constructed and validated a novel preoperative prognostic model that can accurately and conveniently predict the long-term survival of patients with resectable PDAC of pancreatic head. Besides, the model can screen high-risk patients with poor prognosis, which may provide references for personal treatment strategies in the future.
The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from ...seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.
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•11,394 proteins are quantified in autopsy samples from 7 organs in 19 COVID-19 patients•Elevated expression of cathepsin L1 is detected in the COVID-19 lung tissue•Dysregulation of angiogenesis, coagulation, and fibrosis is detected in multiple organs•Systemic metabolic dysregulation is detected in multiple organs
A proteomics analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients shows elevated expression of cathepsin L1, rather than ACE2, in the lung tissue and highlights dysregulation of angiogenesis, coagulation, and fibrosis in multiple organs, in addition to systemic hyperinflammation.
To investigate the relationship between surface microstructure and wear mechanism in D2/U71Mn wheel-rail material under different contact stress conditions, rolling wear tests using a GPM-40 wear ...machine to simulate the wheel-rail operation was performed. After wear tests, an optical microscope (OM), scanning electron microscope (SEM) and micro-hardness testers were used to characterize the microstructure and fatigue wear cracks. The results show that the thickness of the plastic deformation layer and surface hardness is increased with the increase of contact stress. Under high contact stress condition (1200 MPa), the severe plastic deformation layer led to the formation of fatigue wear of wheel-rail samples. Under a contact stress of 700 MPa, the wear mechanism of samples is adhesive wear and wear rate is low. With the increase of contact stress, the fatigue cracks are gradually severe. Under a contact stress of 1200 MPa, the wear mechanism of samples becomes fatigue wear and the fatigue wear cracks cause the increase of wear rate. The fatigue wear can accelerate the wear failure of wheel-rail samples. The fatigue wear cracks of wheel samples are severer than that of rail samples due to both the rate of plastic strain and the content of proeutectoid ferrite.
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