Numerical validation of a damage diagnosis method for arch bridges hangers

This paper proposes a test method for damage diagnosis of arch bridge hangers. The acceleration response of every hanger under pulse excitation before and after damage is collected and used to extract the damage feature in time domain directly. Then the damage feature waveform before and after damage is obtained respectively by connecting these damage feature values of all measured hangers one by one. Finally the mean value of normalized curvature difference of damage feature waveforms before and after damage is considered as the damage index to diagnose the hangers. The proposed method has a high sensitivity to small damage and the damage sensitivity has no obvious change to hangers with different lengths; moreover, the proposed method doesn’t require the finite element model of the arch bridge. All of these lay a good foundation for damage diagnosis of arch bridge hangers

Phosphatidylserine phospholipase A1 enables GPR34-dependent immune cell accumulation in the peritoneal cavity.

The peritoneal cavity (PerC) is an important site for immune responses to infection and cancer metastasis. Yet few ligand-receptor axes are known to preferentially govern immune cell accumulation in this compartment. GPR34 is a lysophosphatidylserine (lysoPS)-responsive receptor that frequently harbors gain-of-function mutations in mucosa-associated B cell lymphoma. Here, we set out to test the impact of a GPR34 knock-in (KI) allele in the B-lineage. We report that GPR34 KI promotes the PerC accumulation of plasma cells (PC) and memory B cells (MemB). These KI cells migrate robustly to lysoPS ex vivo, and the KI allele synergizes with a Bcl2 transgene to promote MemB but not PC accumulation. Gene expression and labeling studies reveal that GPR34 KI enhances PerC MemB proliferation. Both KI PC and MemB are specifically enriched at the omentum, a visceral adipose tissue containing fibroblasts that express the lysoPS-generating PLA1A enzyme. Adoptive transfer and chimera experiments revealed that KI PC and MemB maintenance in the PerC is dependent on stromal PLA1A. These findings provide in vivo evidence that PLA1A produces lysoPS that can regulate GPR34-mediated immune cell accumulation at the omentum

Platelets and mast cells promote pathogenic eosinophil recruitment during invasive fungal infection via the 5-HIAA-GPR35 ligand-receptor system

Cryptococcus neoformans is the leading cause of fungal meningitis and is characterized by pathogenic eosinophil accumulation in the context of type-2 inflammation. The chemoattractant receptor GPR35 is expressed by granulocytes and promotes their migration to the inflammatory mediator 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. Given the inflammatory nature of cryptococcal infection, we examined the role of GPR35 in the circuitry underlying cell recruitment to the lung. GPR35 deficiency dampened eosinophil recruitment and fungal growth, whereas overexpression promoted eosinophil homing to airways and fungal replication. Activated platelets and mast cells were the sources of GPR35 ligand activity and pharmacological inhibition of serotonin conversion to 5-HIAA, or genetic deficiency in 5-HIAA production by platelets and mast cells resulted in more efficient clearance of Cryptococcus. Thus, the 5-HIAA-GPR35 axis is an eosinophil chemoattractant receptor system that modulates the clearance of a lethal fungal pathogen, with implications for the use of serotonin metabolism inhibitors in the treatment of fungal infections

Inflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodes.

Sustained lymphocyte migration from blood into lymph nodes (LNs) is important for immune responses. The CC-chemokine receptor-7 (CCR7) ligand CCL21 is required for LN entry but is downregulated during inflammation, and it has been unclear how recruitment is maintained. Here, we show that the oxysterol biosynthetic enzyme cholesterol-25-hydroxylase (Ch25h) is upregulated in LN high endothelial venules during viral infection. Lymphocytes become dependent on oxysterols, generated through a transcellular endothelial-fibroblast metabolic pathway, and the receptor EBI2 for inflamed LN entry. Additionally, Langerhans cells are an oxysterol source. Ch25h is also expressed in inflamed peripheral endothelium, and EBI2 mediates B cell recruitment in a tumor model. Finally, we demonstrate that LN CCL19 is critical in lymphocyte recruitment during inflammation. Thus, our work explains how naive precursor trafficking is sustained in responding LNs, identifies a role for oxysterols in cell recruitment into inflamed tissues, and establishes a logic for the CCR7 two-ligand system

Iurnal Variability of Airway Hyperresponsiveness in Asthma Patients

BackgroundThere are daytime variability in pulmonary function indexes such as peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) in asthma patients. Studies evaluating the effects of drug therapy on lung function and airway hyperresponsiveness (AHR) in asthma patients all required patients to perform spirometry and bronchial challenge test in the same time point of the days. However, whether there is a daily diurnal AHR variability is still not clear.ObjectiveTo explore the characteristics and diurnal variability of AHR in asthma patients.MethodsThe data of 202 patients with asthma who consulted in respiratory department of the First Affiliated Hospital of Guangzhou Medical University from January 2018 to September 2020 were included for statistical analysis. All patients completed the methacholine bronchial provocation tests, they were divided into the morning detection group (morning group) with 81 cases and the afternoon detection group (afternoon group) with 121 cases; according to the disease course, 98 cases were divided into the initial diagnosis group if the disease course was ≤6 months, and 104 cases were divided into the follow-up group if the disease course was >6 months. The initial diagnosis group and the follow-up group were divided into the initial diagnosis morning group, the initial diagnosis afternoon group, the follow-up morning group, and the follow-up afternoon group according to the detection time; according to the AHR, the patients were divided into very mild, mild, moderate and severe groups. The characteristics of AHR and the main pulmonary function indexes including FVC%pred, FEV1%pred, PEF%pred, MMEF%pred, MEF50%pred, MEF25%pred, PD20-FEV1, PD20-PEF, PD20-MMEF, PD20-MEF25%, PD20-MEF50% of these groups were analyzed and compared.ResultsThere were no significant differences of the math pulmonary function indexes and PD20 between morning and afternoon groups (P<0.05) . FEV1%pred and PD20-PEF were significantly higher in initial diagnosed group than follow-up group (P<0.05) . There was no significant difference in FVC%pred, PEF%pred, MMEF%pred, MEF50%pred, MEF25%pred, PD20-FEV1, PD20-MMEF, PD20-MEF25%, and PD20-MEF50% between the initial visit group and the follow-up visit group (P>0.05) . In follow-up group, MMEF%pred and MEF50%pred were higher in afternoon than in morning (P<0.05) . There were no differences of lung function and AHR between morning and afternoon in initial diagnosed group (P<0.05) . No obvious correlations were found between disease history and PD20. There were no significant differences of PD20-FEV1 between the morning and afternoon, initial diagnosed and follow-up (P>0.05) .ConclusionThe longer the duration of asthma, more serious impairment of lung function found in asthma, while the AHR had no significant difference between morning and afternoon

Inhibition of Extracellular Signal-Regulated Kinases Ameliorates Hypertension-Induced Renal Vascular Remodeling in Rat Models

The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2) inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs) and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries

Loss of signalling via Gα13 in germinal center B-cell-derived lymphoma

Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined1,2. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells3,4. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma

Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers

Selective ablation of follicular dendritic cells in mice results in disorganization of primary follicles and dispersal of B cells out of splenic germinal centers