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Idiopathic pulmonary fibrosis (IPF) is the most common and fatal diffuse fibrotic lung disease accompanied by macrophage M2 activation. ErbB4 is involved in and affects the process of inflammation. In this study, we determined that the mRNA level and protein expression of ErbB4 and M2 cytokine members were increased in the serum of IPF patients. In mouse alveolar macrophage MH-S cells, after knocking down ErbB4 by siRNA, the mRNA level and protein expression of M2 activator induced by interleukin (IL)-4 were decreased compared with the control group. Activating by ErbB4 agonist neuromodulatory protein (NRG)-1, IL-4-induced M2 program was promoted. Mechanistically, treated with NRG-1 in MH-S cells, the phosphorylation level of Akt did not change, while the phosphorylation level of ERK increased. Using SCH772984 to inhibit ERK pathway, the increasing IL-4-induced M2 activation by NRG-1 was inhibited, and the high level of M2 activator protein expression and mRNA expression was restored. Collectively, our data support that ErbB4 and M2 programs are implicated in IPF, and ErbB4 participates in the regulation of M2 activation induced by IL-4 through the ERK pathway.

This study investigates the enhancement of hydraulic lime mortar (HLM) using varying contents of metakaolin (MK) to improve its application in the restoration of historic buildings. Samples from historic structures were analyzed, and the effects of different MK contents on the physical and mechanical properties of HLM were examined. The reaction mechanism and microstructural changes were evaluated using XRD and SEM analysis. The results indicated that increasing MK levels in HLM led to a decrease in fluidity, with fluidity reducing by 4.8% at 12% MK. The addition of MK increased water consumption for standard consistency by 5.4% and shortened the final setting time by 10.2%. MK consumption promoted secondary hydration, enhancing compressive strength by up to 98.1% and flexural strength by up to 55.1%, and increasing bonding strength by 26.9%. The density of HLM improved with MK addition, slightly reducing moisture content by 4.5% and water absorption by 4.6%, while the water vapor transmission properties decreased by 50.9%, indicating reduced porosity. The elastic modulus of the mortar increased significantly from 2.19 GPa to 7.88 GPa with the addition of MK, enhancing rigidity and crack resistance. The optimal blend for restoration materials was found to be 9.0% MK and 25.0% heavy calcium carbonate and was characterized by moderate mechanical strength, enhanced early strength, commendable permeability, minimal risk of cracking, and ease of application. This blend is highly suitable for the rehabilitation of historic structures. [ABSTRACT FROM AUTHOR]

AbstractBackground Prostate cancer (PCa) is poor response to the immunotherapy for its high heterogeneity of immune microenvironment. In this study, we aim to introduce a new immune subtype for PCa involving M2 tumour associated macrophages (M2-TAMs).Methods Three hundred and sixty-two PCa patients and matched normal prostate tissues were selected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Patients’ immune infiltration characters were then analyzed based on the gene expressions. The immune subtypes were identified by the method of unsupervised hierarchical clustering. Finally, the relationship between the M2-TAMs infiltration and anti-programmed death-ligand-1 (PD-L1) therapy was investigated in the IMvigor210 cohort.Results PCa expressed lower immune-related genes levels compared with the adjacent normal tissues. Based on the proved immunosuppressive mechanisms in PCa, tumour patients were classified into three independent subclasses with high infiltrated cytolytic activity (CYT), M2-TAMs and regulatory T cell (Tregs), respectively. Among these subtypes, M2-TAMs infiltration subtype showed the worst clinicopathological features and prognosis compared with the other two subtypes. The results of the IMvigor210 cohort demonstrated poor response of anti-PD-L1 therapy for patients with high M2-TAMs infiltration.Conclusion Prostate tumours involved in significant immunosuppression, and high infiltration of M2-TAMs can be applied to predict the effect of anti-PD-L1 therapy.Key MessagesPCa patients can be classified into three immunotypes of high infiltrated CYT, M2-TAMS, and Tregs according to the immunosuppressive mechanisms.High M2-TAMs infiltration subtype reflected the worst clinical characters, immune infiltration, and lowest expression of immune checkpoint inhibitors among the three subclasses in PCa.High M2-TAMs infiltration predicts the low response rate of anti-PD-L1 therapy.

N6-methyladenosine (m6A) plays a role in various diseases, but it has rarely been reported in acute lung injury (ALI). The FTO (fat mass and obesity-associated) protein can regulate mRNA metabolism by removing m6A residues. The aim of this study was to examine the role and mechanism of the m6A demethylase FTO in LPS-induced ALI. Lung epithelial FTO-knockout mice and FTO-knockdown/overexpression human alveolar epithelial (A549) cell lines were constructed to evaluate the effects of FTO on ALI. Bioinformatics analysis and a series of in vivo and in vitro assays were used to examine the mechanism of FTO regulation. Rescue assays were conducted to examine whether the impact of FTO on ALI depended on the TXNIP/NLRP3 pathway. In LPS-induced ALI, RNA m6A modification amounts were upregulated, and FTO expression was downregulated. In vivo, lung epithelial FTO knockout alleviated alveolar structure disorder, tissue edema, and pulmonary inflammation and improved the survival of ALI mice. In vitro, FTO knockdown reduced A549 cell damage and death induced by LPS, whereas FTO overexpression exacerbated cell damage and death. Mechanistically, bioinformatics analysis revealed that TXNIP was a downstream target of FTO. FTO deficiency mitigated pyroptosis in LPS-induced ALI via the TXNIP/NLRP3 pathway. Rescue assays confirmed that the impact of FTO on the TXNIP/NLRP3 pathway was significantly reversed by the TXNIP inhibitor SRI-37330. Deficiency of FTO alleviates LPS-induced ALI via TXNIP/NLRP3 pathway–mediated alveolar epithelial cell pyroptosis, which might be a novel therapeutic strategy for combating ALI. [ABSTRACT FROM AUTHOR]

Sensor-related indoor localization has attracted considerable attention in recent years. The accuracy of conventional fingerprint solutions based on a single sensor, such as a Wi-Fi sensor, is affected by multipath interferences from other electronic devices that are produced as a result of complex indoor environments. Light sensors and magnetic (i.e., geomagnetic) field sensors can be used to enhance the accuracy of a system since they are less vulnerable to disturbances. In this paper, we propose a deep feedforward (DFF)-neural-network-based method, termed DFF-WGL, which integrates the data from the embedded Wi-Fi sensor, geomagnetic field sensor, and light sensor (WGL) in a smart device to localize the device in an indoor environment. DFF-WGL does not require complex and expensive auxiliary equipment, except for basic fluorescent lamps and low-density Wi-Fi signal coverage, conditions that are easily satisfied in modern offices or educational buildings. The proposed system was implemented on a commercial off-the-shelf android device, and performance was evaluated through an experimental analysis conducted in two different indoor testbeds, one measuring 60.5 m2 and the other measuring 38 m2, with 242 and 60 reference points, respectively. The results indicate that the model prediction with an input consisting of the combination of light, a magnetic field sensor, and two Wi-Fi RSS signals achieved mean localization errors of 0.01 m and 0.04 m in the two testbeds, respectively, compared with any subset of combination of sensors, verifying the effectiveness of the proposed DFF-WGL method. [ABSTRACT FROM AUTHOR]