Analysis and prediction of compressive and split-tensile strength of secondary steel fiber reinforced concrete based on RBF fuzzy neural network model.

Accurate analysis of the strength of steel-fiber-reinforced concrete (SFRC) is important for ensuring construction quality and safety. Cube compression and splitting tensile tests of steel fiber with different varieties, lengths, and dosages were performed, and the effects of different varieties, lengths, and dosages on the compressive and splitting properties of secondary concrete were obtained. It was determined that the compression and splitting strengths of concrete could be effectively improved by the addition of end-hooked and milled steel fibers. The compressive and splitting strengths of concrete can be enhanced by increasing the fiber length and content. However, concrete also exhibits obvious uncertainty owing to the comprehensive influence of steel fiber variety, fiber length, and fiber content. In order to solve this engineering uncertainty, the traditional RBF neural network is improved by using central value and weight learning strategy especially. On this basis, the RBF fuzzy neural network prediction model of the strength of secondary steel fiber-reinforced concrete was innovatively established with the type, length and content of steel fiber as input information and the compressive strength and splitting tensile strength as output information. In order to further verify the engineering reliability of the prediction model, the compressive strength and splitting tensile strength of steel fiber reinforced concrete with rock anchor beams are predicted by the prediction model. The results show that the convergence rate of the prediction model is increased by 15%, and the error between the predicted value and the measured value is less than 10%, which is more efficient and accurate than the traditional one. Additionally, the improved model algorithm is efficient and reasonable, providing technical support for the safe construction of large-volume steel fiber concrete projects, such as rock anchor beams. The fuzzy random method can also be applied to similar engineering fields.

Discoidin domain receptor 2 signaling through PIK3C2α in fibroblasts promotes lung fibrosis.

Pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), portends significant morbidity and mortality, and current therapeutic options are suboptimal. We have previously shown that type I collagen signaling through discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase expressed by fibroblasts, is critical for the regulation of fibroblast apoptosis and progressive fibrosis. However, the downstream signaling pathways for DDR2 remain poorly defined and could also be attractive potential targets for therapy. A recent phosphoproteomic approach indicated that PIK3C2α, a poorly studied member of the PI3 kinase family, could be a downstream mediator of DDR2 signaling. We hypothesized that collagen I/DDR2 signaling through PIK3C2α regulates fibroblast activity during progressive fibrosis. To test this hypothesis, we found that primary murine fibroblasts and IPF-derived fibroblasts stimulated with endogenous or exogenous type I collagen led to the formation of a DDR2/PIK3C2α complex, resulting in phosphorylation of PIK3C2α. Fibroblasts treated with an inhibitor of PIK3C2α or with deletion of PIK3C2α had fewer markers of activation after stimulation with TGFß and more apoptosis after stimulation with a Fas-activating antibody. Finally, mice with fibroblast-specific deletion of PIK3C2α had less fibrosis after bleomycin treatment than did littermate control mice with intact expression of PIK3Cα. Collectively, these data support the notion that collagen/DDR2/PIK3C2α signaling is critical for fibroblast function during progressive fibrosis, making this pathway a potential target for antifibrotic therapy. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Exponential synchronization of delayed coupled neural networks with delay-compensatory impulsive control.

This paper studies the exponential synchronization problem for a class of delayed coupled neural networks with delay-compensatory impulsive control. A Razumikhin-type inequality involving some destabilizing delayed impulse gains and a new idea of delay-compensatory that shows two critical roles for system stability are presented, respectively. Based on the constructed inequality and the presented delay-compensatory idea, sufficient stability and synchronization criteria for globally exponential synchronization (GES) of coupled neural networks (CNNs) are presented. Compared with existing results, the uniqueness of the presented results lies in that impulse delays can be fetched and integrated to compensate for instantaneous unstable impulse dynamics caused by destabilizing gains. Moreover, constraints between system delay and impulsive delay are relaxed, and the interval of impulses no longer constrains the system delay. Comparisons and a practical application are given to demonstrate the superior performance of the presented novel control methods.

CD36/Lyn kinase interactions within macrophages promotes pulmonary fibrosis in response to oxidized phospholipid.

Recent data from human studies and animal models have established roles for type II alveolar epithelial cell (AEC2) injury/apoptosis and monocyte/macrophage accumulation and activation in progressive lung fibrosis. Although the link between these processes is not well defined, we have previously shown that CD36-mediated uptake of apoptotic AEC2s by lung macrophages is sufficient to drive fibrosis. Importantly, apoptotic AEC2s are rich in oxidized phospholipids (oxPL), and amongst its multiple functions, CD36 serves as a scavenger receptor for oxPL. Recent studies have established a role for oxPLs in alveolar scarring, and we hypothesized that uptake and accrual of oxPL by CD36 would cause a macrophage phenotypic change that promotes fibrosis. To test this hypothesis, we treated wild-type and CD36-null mice with the oxPL derivative oxidized phosphocholine (POVPC) and found that CD36-null mice were protected from oxPL-induced scarring. Compared to WT mice, fewer macrophages accumulated in the lungs of CD36-null animals, and the macrophages exhibited a decreased accumulation of intracellular oxidized lipid. Importantly, the attenuated accrual of oxPL in CD36-null macrophages was associated with diminished expression of the profibrotic mediator, TGFß. Finally, the pathway linking oxPL uptake and TGFß expression was found to require CD36-mediated activation of Lyn kinase. Together, these observations elucidate a causal pathway that connects AEC2 injury with lung macrophage activation via CD36-mediated uptake of oxPL and suggest several potential therapeutic targets.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

Inhibition of discoidin domain receptor 2 reveals kinase-dependent and kinase-independent functions in regulating fibroblast activity.

Progressive pulmonary fibrosis is a devastating condition and current treatment is suboptimal. There has been considerable interest in the role of tyrosine kinase signaling as mediators of pro- and antifibrotic processes. Nintedanib is a nonspecific tyrosine kinase that has been shown to have therapeutic benefit in lung fibrosis. However, the precise mechanism of action remains unclear because nintedanib inhibits several tyrosine kinases, which are often expressed on multiple cell types with different activities during fibrosis. Discoidin domain receptor 2 (DDR2) has been suggested as a potential target of nintedanib. DDR2 is a receptor tyrosine kinase that is activated by fibrillar collagens such as type I collagen. DDR2 is primarily expressed by fibroblasts. The effectiveness of specifically targeting DDR2 signaling during fibrosis remains undefined. In the present study, we show that nintedanib acts as a direct and indirect inhibitor of DDR2. We then utilize a novel allosteric inhibitor of DDR2, WRG-28, which blocks ligand binding and activation of DDR2. We find that WRG-28 augments fibroblast apoptosis and attenuates fibrosis. Finally, we show that fibroblast type I collagen autocrine signaling is regulated by DDR2 through both kinase-dependent and kinase-independent functions of DDR2. These findings highlight the importance of type I collagen autocrine signaling by fibroblasts during fibrosis and demonstrate that DDR2 has a central role in this pathway making it a potential therapeutic target.NEW & NOTEWORTHY Type I collagen is a major component of fibrosis and can signal through cell surface receptors such as discoidin domain receptor 2 (DDR2). DDR2 activation can lead to further collagen deposition by fibroblasts setting up a profibrotic positive feedback loop. In this report, we find that inhibition of DDR2 with nintedanib or a specific DDR2 inhibitor, WRG-28, can disrupt this cycle and prevent fibrosis through augmented fibroblast apoptosis and inhibited activation.

Catheterization Before Transperineal Ultrasound-guided Prostate Biopsy and the Risk of Urethrorrhagia.

OBJECTIVE: To investigate the efficacy of catheterization before transperineal ultrasound-guided prostate biopsy in reducing risk of urethrorrhagia. Currently, transperineal ultrasound-guided prostate biopsy (TPPB) is one of the most commonly used measures to help diagnose prostate cancer. However, whether the retention of catheterization before transperineal ultrasound-guided prostate biopsy is associated with the reduced risk of urethrorrhagia remains uncertain. METHODS: A cohort study was conducted in our hospital from January 2021 to September 2021. This study included 93 patients who participated in transperineal ultrasound-guided prostate biopsy. We compared the risk of urethrorrhagia in patients who underwent indwelling catheterization before biopsy and those who did that after biopsy, and performed an unadjusted analysis. We also analyzed the use of related confounding factors to limit the cohort of men, and applied propensity-score adjustment to control potential confounders. Analyses that restricted the cohort men with the related confounding factors and that used propensity-score adjustment to control for potential confounders. RESULTS: A total of 93 men were recruited in the cohort study, and the numbers of patients in group 1 and group 2 were 64 and 29, respectively. There were 34 patients (53.1%) of urethrorrhagia in group 1, and 22 patients (75.8%) of urethrorrhagia in group 2. This was a significant difference between the 2 groups (P = .008). After adjusting for correlative factors, the preoperative catheterization is still a protective factor for postoperative urethrorrhagia through multivariate multiple piecewise linear regression analysis. CONCLUSION: The result of this cohort study suggested that preoperative catheterization can significantly reduce the risk of urethrorrhagia.

Association between anesthesia technique and complications after hip surgery in the elderly population.

BACKGROUND: Spinal anesthesia is superior to general anesthesia for postoperative recovery in older patients (≥ 65 age). However, evidence for this is lacking. AIM: To evaluate the effect of anesthesia on postoperative complications in older patients undergoing hip surgery. METHODS: This is a retrospective, propensity score-matched, cohort study. Patients ≥ 65-years-old who underwent hip surgery at the Traditional Chinese Medicine of Guangdong Provincial Hospital in China from October 2016 to June 2020 were included. The operative methods were femoral fracture's internal fixation and hip replacement. The orthopedic doctors in different hospitals of our group have varied requirements for patients' out-of-bed time after surgery. Therefore, spinal anesthesia or general anesthesia was selected according to the requirements of the orthopedic doctors. The primary outcome of this study was complications during the hospitalization of the postoperative patient. The length of hospital stay, postoperative blood transfusion, routine blood analysis, renal function, coagulation function, and inflammatory correlations were secondary outcomes. Propensity score matching (PSM) was performed utilizing logistic regression. RESULTS: Among the 864 patients identified from the electronic medical record data database, we screened out those with incomplete medical record data. After PSM of the baseline values of the two groups of patients, data of 309 patients (206 patients in spinal anesthesia group and 103 patients in general anesthesia) were utilized in this study. 67/309 patients had complications, including postoperative limb dysfunction, pulmonary infection, delirium, lower extremity venous thrombosis, and shock. The incidence of complications was not related to anesthesia methods (P > 0.05), but the levels of D-Dimer (P = 0.017), fibrinogen (P = 0.005), and high-sensitivity C-reactive protein (hsCRP) (P = 0.002) in the spinal anesthesia group were significantly higher than those in the general anesthesia group. CONCLUSION: Anesthesia technology is not a risk factor for postoperative complications of hip surgery. The levels of D-Dimer and hsCRP were higher in the spinal anesthesia group.

Hydrochemical patterns indicating hydrological processes with the background of changing climatic and environmental conditions in China: a review.

In the background of global climate and environmental change, the hydrochemical characteristics of water bodies present significant instability to all regions, including humid, arid, and alpine ones. There are two main reasons for this: (1) climate change has altered the temporal and spatial distribution of precipitation, and climate warming intensified the mutual transformation of water bodies. The temperature in China increased by 0.29 °C/10a from 1951 to 2018. For different regions, whether the alpine region (0.37 °C/10a, P < 0.05), the arid region (0.278 °C/10a, P < 0.05), or the humid region (0.168 °C/10a, P < 0.05), there was a significant increasing trend (P < 0.05) from 1951 to 2018. Thus, the characteristics of water recharge sources and the hydrological processes and hydrochemical characteristics of water bodies are affected. Increase in precipitation increases the input sources for water transformation, intensifying the transformation of water bodies. (2) In the context of climate and environmental change, human activities and the local environment are seriously affecting the transformation of various water bodies and hydrochemical ion sources. The comprehensive effects of various physical and geographical conditions, geological structure, lithology and transformation, and recharge of various water bodies affect the hydrochemical characteristics of water bodies in China. The differences in the type of water bodies showed that the hydrochemical process of water bodies was more complex, although there was a hydraulic connection between precipitation, river water, lake water, and groundwater. This provides a new idea for the future study of hydrochemical characteristics and hydrology.

Bulk phosphorous deposition at four typical land use sites in Southwest China.

Whilst ongoing increases in the deposition of atmospheric nitrogen (N) in China have attracted a lot of attention, to date there has been little research on phosphorus (P) deposition. In this study, we quantified inorganic P (PO43-), dissolved organic P (DOP) and total P (TP) in bulk deposition at four sites in the Sichuan Basin, Southwest China. Chengdu (CD), Shifang (SF), Yanting (YT), and Gongga (GG). They represent the land use categories urban, suburban, agricultural and forest, respectively, during 2008-2018 at CD and YT, 2015-2018 at SF, and 2007-2014 at GG. Annual average TP concentrations (deposition rates) were 0.07 (0.61), 0.49 (3.22), 0.17 (1.07) and 0.01 (0.20) mg L-1 (kg ha-1 yr-1), at CD, SF, YT and GG, respectively. The TP concentrations at YT and GG showed significant increasing trends over the years, with very little change at CD and a decline at SF because of the implementation of environmental control measures. Average PO43- to DOP ratios were 0.65, 0.95, 0.82 and 0.81 at CD, SF, YT and GG, respectively, indicating that DOP accounts for a higher proportion at the urban site, and dominated by combustion sources. Bulk P deposition showed higher deposition rates in summer and lower in winter. These results highlight the importance of long term monitoring in detecting spatial and temporal changing trends of the chemical composition, so as to implement effective policies to eliminate air pollution, especially for Southwest China, where there is limited research on atmospheric P deposition.

A high-throughput cell-based gaussia luciferase reporter assay for measurement of CYP1A1, CYP2B6, and CYP3A4 induction.

The induction of cytochrome P450s can result in reduced drug efficacy and lead to potential drug-drug interactions. The xenoreceptors-aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR)-play key roles in CYP induction by xenobiotics. In order to be able to rapidly screen for the induction of three enzymes (CYP1A1, CYP2B6, and CYP3A4), we generated a stable AhR-responsive HepG2 cell line, a stable CAR-responsive HepG2 cell line, and a stable PXR-responsive HepG2 cell line.To validate these stable xenoreceptor-responsive HepG2 cell lines, we evaluated the induction of the different Gaussia reporter activities, as well as the mRNA and protein expression levels of endogenous CYPs in response to different inducers.The induction of luciferase activity in the stable xenoreceptor-responsive HepG2 cell lines by specific inducers occurred in a concentration dependent manner. There was a positive correlation between the induction of luciferase activities and the induction endogenous CYP mRNA expression levels. These xenoreceptor-responsive HepG2 cell lines were further validated with known CYP1A1, CYP2B6, and CYP3A4 inducers.These stable xenoreceptor-responsive HepG2 cell lines may be used in preclinical research for the rapid and sensitive detection of AhR, CAR, and PXR ligands that induce CYP450 isoforms.

Circular RNA circANKS1B acts as a sponge for miR-152-3p and promotes prostate cancer progression by upregulating TGF-α expression.

BACKGROUND: A growing number of studies indicate that circular RNAs (circRNAs) play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aimed to investigate the expression and function of circANKS1B in prostate cancer (PC). METHODS: The expression of circANKS1B and miR-152-3p was analyzed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell migration and invasion were measured using a transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by a dual-luciferase reporter gene assay. Rescue experiments were conducted to determine whether circANKS1B regulated the invasion of PC cells via the circANKS1B-miR-152-3p-TGF-α pathway. RESULTS: The expression of circANKS1B was markedly upregulated in both PC cells and tissues. Moreover, high circANKS1B expression was associated with poor prognosis in PC patients. Dual-luciferase reporter assay indicated that circANKS1B directly bound to miR-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B markedly suppressed cell migration and invasion and TGF-α expression in PC cells, whereas the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on invasion of circANKS1B-deficient PC cells was also abrogated by TGF-α deficiency. Overall, circANKS1B acts as a sponge for miR-152-3p to promote PC progression by upregulating TGF-α expression. CONCLUSION: Our findings reveal that circANKS1B may be a potential prognostic biomarker and therapeutic target for PC.

[Clinical effect of an additional maintenance dose of caffeine before ventilator weaning in preterm infants with respiratory distress syndrome: a prospective randomized controlled trial].

OBJECTIVE: To study the clinical effect of an additional maintenance dose (5 mg/kg) of caffeine citrate injection at 1 hour before ventilator weaning in improving the success rate of ventilator weaning in preterm infants (gestational age ≤32 weeks) with respiratory distress syndrome (RDS) on mechanical ventilation. METHODS: A total of 338 preterm infants with RDS (gestational age of ≤32 weeks) who were admitted to the Neonatal Intensive Care Unit of Xiamen Maternal and Child Health Hospital from January 2017 to December 2019 and treated with mechanical ventilation were enrolled. They were randomly divided into an observation group and a routine group, with 169 infants in each group. Both groups received early routine treatment with caffeine. The infants in the observation group received an additional maintenance dose of caffeine citrate injection at 1 hour before ventilator weaning. The two groups were compared in terms of reintubation rate and number of apnea episodes within 48 hours after ventilator weaning, changes in blood gas parameters, blood glucose, heart rate, and mean blood pressure at 2 hours after ventilator weaning, and incidence rates of major complications during hospitalization. RESULTS: Compared with the routine group, the observation group had significantly lower reintubation rate (P=0.034) and number of apnea episodes (≥2 times/day) (P=0.015) within 48 hours after ventilator weaning. Compared with the routine group at 2 hours after ventilator weaning, the observation group had a significantly higher pH value and a significantly lower arterial partial pressure of carbon dioxide (P < 0.05), while there were no significant differences between the two groups in arterial partial pressure of oxygen, blood glucose, heart rate, and mean blood pressure (P > 0.05). During hospitalization, the observation group had a significantly lower incidence rate of intraventricular hemorrhage than the routine group (P=0.048), but there were no significant differences between the two groups in the incidence rates of bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, and periventricular leukomalacia and mortality rate (P > 0.05). CONCLUSIONS: An additional maintenance dose of caffeine citrate injection at 1 hour before ventilator weaning is safe and effective in improving the success rate of ventilator weaning in preterm infants with RDS and thus holds promise for clinical application.

CD200-CD200R1 signaling pathway regulates neuroinflammation after stroke.

OBJECTIVE: To study how the CD200-CD200R1 signaling pathway modulates poststroke inflammation and advances our knowledge of immune responses to ischemia insults in stroke. METHODS: Focal middle cerebral artery occlusion (MCAO) was induced in mice for 90 min, and mice were sacrificed at 1, 3, and 7 days of reperfusion. CD200, CD200R1, iNOS, and Arg-1 expression in ischemic brains was assessed by Western blotting (WB), and immunohistochemical (IHC) staining was performed to examine the expression of CD200 on neurons and CD200R1 on infiltrating lymphocytes. The severity of neurobehavioral deficits was evaluated by neurological deficit scores (NDS) and infarction volume estimated by TTC staining. To study the relationship between CD200/CD200R1 expression and the diversity of the neuroinflammatory response in stroke, CD200Fc (CD200R1 agonist) was subcutaneously injected at onset, at 1 day and 2 days after MCAO operation, and the brains were collected for detection at 3 days after MCAO/R (reperfusion). RESULTS: CD200 expression on neurons increased at 1 day and then decreased at 3 days after MCAO/R, and the expression of CD200R1 on lymphocytes showed an opposite temporal pattern as tested by IHC. The WB results showed that CD200/CD200R1 variance exhibited a similar pattern of IHC results, and the level of iNOS peaked at 1 day and then decreased gradually, but Arg-1 increased with time after MCAO/R in ischemic brains. After CD200Fc injection, CD200R1 expression significantly increased, and CD200Fc promoted Arg-1 but inhibited iNOS expression. The infarct volume and NDS of the group treated with CD200Fc were significantly smaller than those of the IgG2a-treated group. CONCLUSIONS: The CD200-CD200R1 signaling pathway regulates neuroinflammation after stroke. Stimulation of CD200R1 by CD200Fc promotes the anti-inflammatory response and alleviates ischemic injury.

[Community of Benthic Diatoms and Their Relationship with Aquatic Environmental Factors in the Tangwang River, China].

To reasonably evaluate the eco-environmental health of the Tangwang River, which is a tributary of the Songhua River in China, community structures of periphyton and cleanliness of the benthic diatom at 24 sampling sites were investigated using McNaughton's dominance index, clustering, and ecotype analysis, while the relationship between the environmental factors and the diatom communities were studied by principal component analysis, Spearman correlation test, and redundancy analysis, in August 2018 (flood season). A total of 99 species or variants of benthic diatoms have been identified, indicating that there were abundant diatoms in the Tangwang River. Achnanthidium minutissimum and other diatoms that can be used as clean water indicators were dominant species in the Tangwang River, which indicates that the eco-environmental quality of the Tangwang River was relatively healthy in the flood season. Of these, the dominant degree of A. minutissimum was 0.32, making it the absolute dominant species in Tangwang River. Sampling sites can be divided into three groups based on clustering analysis. The dominant species of group 1 and group 2 were mainly clean species, indicating that the two groups were in a relatively healthy state. Nitzschia palea, Ulnaria ulna, and other diatoms that can be used as eutrophication indicators were the dominant species of group 3, indicating that group 3 was less healthy than the other two groups. From groups 1 and 2, the results from ecotype analysis showed a decrease in the proportion of polyoxybiontic diatoms and an increase in the proportion of α-mesosaphrobe diatoms, polysaprobe diatoms, oligo-mesotrophic diatoms, mesotrophic diatoms, meso-eutrophic diatoms, and eutrophic diatoms. Compared to the other two groups, the results from ecotype analysis showed a significant increase in the proportion of α-mesosaphrobe diatoms, polysaprobe diatoms, eutrophic diatoms and hypereutrophic diatoms in group 3. The predominant aquatic influencing factors of diatom community structures for the Tangwang River were permanganate index, total nitrogen (TN), and ammonia nitrogen (NH4+-N), of which permanganate index was the main factor for group 2, while TN and NH4+-N were the main factors for group 3. As a result, the eco-environmental quality of the Tangwang River was good, and the benthic diatom was found to be an effective indicator of the nutritional conditions and saprophytic status.

Type I Collagen Signaling Regulates Opposing Fibrotic Pathways through α2ß1 Integrin.

Fibrosis is characterized by fibroblast activation, leading to matrix remodeling culminating in a stiff, type I collagen-rich fibrotic matrix. Alveolar epithelial cell (AEC) apoptosis is also a major feature of fibrogenesis, and AEC apoptosis is sufficient to initiate a robust lung fibrotic response. TGF-ß (transforming growth factor-ß) is a major driver of fibrosis and can induce both AEC apoptosis and fibroblast activation. We and others have previously shown that changes in extracellular matrix stiffness and composition can regulate the cellular response to TGF-ß. In the present study, we find that type I collagen signaling promotes TGF-ß-mediated fibroblast activation and inhibits TGF-ß-induced AEC death. Fibroblasts cultured on type I collagen or fibrotic decellularized lung matrix had augmented activation in response to TGF-ß, whereas AECs on cultured on type I collagen or fibrotic lung matrix were more resistant to TGF-ß-induced apoptosis. Both of these responses were mediated by integrin α2ß1, a major collagen receptor. AECs treated with an α2 integrin inhibitor or with deletion of α2 integrin had loss of collagen-mediated protection from apoptosis. We found that mice with fibroblast-specific deletion of α2 integrin were protected from fibrosis whereas mice with AEC-specific deletion of α2 integrin had more lung injury and a greater fibrotic response to bleomycin. Intrapulmonary delivery of an α2 integrin-activating collagen peptide inhibited AEC apoptosis in vitro and in vivo and attenuated the fibrotic response. These studies underscore the need for a thorough understanding of the divergent response to matrix signaling.

Diverse Injury Pathways Induce Alveolar Epithelial Cell CCL2/12, Which Promotes Lung Fibrosis.

Accumulating evidence suggests that fibrosis is a multicellular process with contributions from alveolar epithelial cells (AECs), recruited monocytes/macrophages, and fibroblasts. We have previously shown that AEC injury is sufficient to induce fibrosis, but the precise mechanism remains unclear. Several cell types, including AECs, can produce CCL2 and CCL12, which can promote fibrosis through CCR2 activation. CCR2 signaling is critical for the initiation and progression of pulmonary fibrosis, in part through recruitment of profibrotic bone marrow-derived monocytes. Attempts at inhibiting CCL2 in patients with fibrosis demonstrated a marked upregulation of CCL2 production and no therapeutic response. To better understand the mechanisms involved in CCL2/CCR2 signaling, we generated mice with conditional deletion of CCL12, a murine homolog of human CCL2. Surprisingly, we found that mice with complete deletion of CCL12 had markedly increased concentrations of other CCR2 ligands and were not protected from fibrosis after bleomycin injury. In contrast, mice with lung epithelial cell-specific deletion of CCL12 were protected from bleomycin-induced fibrosis and had expression of CCL2 and CCL7 similar to that of control mice treated with bleomycin. Deletion of CCL12 within AECs led to decreased recruitment of exudate macrophages. Finally, injury to murine and human primary AECs resulted in increased production of CCL2 and CCL12, in part through activation of the mTOR pathway. In conclusion, these data suggest that targeting CCL2 may be a viable antifibrotic strategy once the pathways involved in the production and function of CCL2 and other CCR2 ligands are better defined.

Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis.

The susceptibility to autoimmune diseases is affected by genetic and environmental factors. In rheumatoid arthritis (RA), the shared epitope (SE), a five-amino acid sequence motif encoded by RA-associated HLA-DRB1 alleles, is the single most significant genetic risk factor. The risk conferred by the SE is increased in a multiplicative way by exposure to various environmental pollutants, such as cigarette smoke. The mechanism of this synergistic interaction is unknown. It is worth noting that the SE has recently been found to act as a signal transduction ligand that facilitates differentiation of Th17 cells and osteoclasts in vitro and in vivo. Intriguingly, the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the xenobiotic effects of many pollutants, including tobacco combustion products, has been found to activate similar biologic effects. Prompted by these similarities, we sought to determine whether the SE and AhR signaling pathways interact in autoimmune arthritis. Here we uncovered a nuclear factor kappa B-mediated synergistic interaction between the SE and AhR pathways that leads to markedly enhanced osteoclast differentiation and Th17 polarization in vitro. Administration of AhR pathway agonists to transgenic mice carrying human SE-coding alleles resulted in a robust increase in arthritis severity, bone destruction, overabundance of osteoclasts, and IL17-expressing cells in the inflamed joints and draining lymph nodes of arthritic mice. Thus, this study identifies a previously unrecognized mechanism of gene-environment interaction that could provide insights into the well-described but poorly understood amplification of the genetic risk for RA upon exposure to environmental pollutants.

Environment significance and hydrochemical characteristics of supra-permafrost water in the source region of the Yangtze River.

This paper analyzed the environment significance and hydrochemical characteristics of the main ions on the supra-permafrost water from the view of space-time and different ablations. The study is conducted through collected 330 samples from June to September in 2016 and 2017 in the Source Region of the Yangtze River (SRYR). The results showed the pattern of ionic dominance based on mean value was following as: Cl- > Na+ > SO42- > Ca2+ > Mg2+ > K+ > NO3- > NO2- > NH4+ > F- > Li+. Cl- alone contributed 40.57%, and Cl-, Na+, SO42- and Ca2+ accounted for 94.06% of the total ionic concentrations. The spatial variation of ionic concentration was larger at the initial stage of ablation, and more stable in strong ablation and the end of the ablation stage. The area with elevation of 4500 m was the region where the control source of ions was more sensitive to the hydrochemical characteristics of supra-permafrost water in the study area. Through the analysis of the sources of ions, the anions and cations in supra-permafrost water in the study area were mainly controlled by crustal sources including evaporates rocks and carbonate rocks. The recharge effect of precipitation and snow-melt water only affected the concentration of Cl-, NH4+, NO3-, F-, Li+ and K+, but did not affect NO2-, SO42-, Mg2+ and Ca2+. The hydrochemical type of supra-permafrost water was Ca2+-SO42- in high elevation (>4800 m). However, the hydrochemical type of middle elevation (from 4400 m to 4700 m) was Na+-Cl-. The type of hydrochemistry at low altitude was more complex than at high and middle elevation. This study provides insights on the construction of hydrological models in the cold regions and scientific basis for water resources management in the Tibet Plateaus.