•Geological disasters in hilly areas are related to Land-Use and Land-Cover Changes.•The number of geological disasters in the cultivated land area is the largest.•The point density of geological ...disasters and vegetation coverage is limited.•Geological disasters are more likely to occur in the period of heavy rainfall.•The closer geological disaster to river, the greater probability/scale of occurrence.
Sichuan hilly area is located in southwest China, which have many hilly area, is a densely populated, economically active, frequent geological disasters area. In this paper, Neijiang City in the region is taken as the test sample. This article, which analyzes Land-Use and Land-Cover Changes (LUCC), meteorological and hydrological data from 2015 to 2020, takes Neijiang City in this region as the research object. We explored the relationship between geological disasters such as collapse and landslides that often occur in the natural ecological environment with LUCC and meteorological and hydrological factors, using GIS spatial analysis and statistical analysis methods. The research results indicate that geological disasters mainly occur in farmland areas. The density of geological disaster points is highest within urban areas, making them the most prone to geological disasters. Geological disasters are more densely distributed in the area within 600 to 800 m from the river. There is a strong correlation between the average rainfall amount and the probability of geological disasters occurring. This study provides a scientific basis for the geological disaster risk assessment, prevention and control in this region. It has certain reference significance for the ecological environment governance, land resources planning and management in other similar regions.
A mesoporous TiO
2
–SiO
2
composite was synthesized by a sol–gel process (AcHE: Ac, H, and E represent acetic acid, HCl, and EtOH) using Ti(OBu)
4
and Si(OEt)
4
as the precursors and poly block ...co-polymer F127 as surfactant. The number of the Brønsted acidic sites can be increased via an hybrid process in which a fraction of Si(OEt)
4
was substituted by phenyltrimethoxysilane (PTMS), as evaluated by
31
P solid-state NMR spectroscopy using trimethylphosphine oxide as probe molecules. The acidic property of hybrid TiO
2
–SiO
2
materials can be rationally controlled by regulating the PTMS/Si(OEt)
4
mole ratio.
Wheel flats have become a major problem affecting the long-term service of railway systems. Wheels with flats create intermittent impact loads to trains and rails. This not only accelerates the ...deterioration of vehicle and track components but also leads to abnormal wheel-rail contact conditions. An effective method for detecting wheel conditions is urgently needed to ensure the operation of the railway and provide guidance for the repair of wheels. However, most previous researches have used qualitative detection methods, and hence have been unable to achieve accurate positioning of the wheel flats. In addition, the theoretical basis for the layout scheme for wheel flat detection sensors is lacking, making it impossible to meet the needs of field applications. In this study, we simulated the spatial distribution characteristics of rail strain, under different wheel flat conditions, and based on this, a layout scheme of multisensor arrays was proposed which more effectively captured the responses of the wheel flats. A wheel flat recognition and precise positioning method based on multisensor fusion was designed. The algorithm was validated through the combination of experimental and simulation methods. The result shows that the algorithm can ideally detect and locate the wheel flats under complex conditions.
Accumulating evidence has proven that N6-methyladenosine (m
6
A) RNA methylation plays an essential role in tumorigenesis. However, the significance of m
6
A RNA methylation modulators in the ...malignant progression of papillary renal cell carcinoma (PRCC) and their impact on prognosis has not been fully analyzed. The present research set out to explore the roles of 17 m
6
A RNA methylation regulators in tumor microenvironment (TME) of PRCC and identify the prognostic values of m
6
A RNA methylation regulators in patients afflicted by PRCC. We investigated the different expression patterns of the m
6
A RNA methylation regulators between PRCC tumor samples and normal tissues, and systematically explored the association of the expression patterns of these genes with TME cell-infiltrating characteristics. Additionally, we used LASSO regression to construct a risk signature based upon the m
6
A RNA methylation modulators. Two-gene prognostic risk model including IGF2BP3 and HNRNPC was constructed and could predict overall survival (OS) of PRCC patients from the Cancer Genome Atlas (TCGA) dataset. The prognostic signature-based risk score was identified as an independent prognostic indicator in Cox regression analysis. Moreover, we predicted the three most significant small molecule drugs that potentially inhibit PRCC. Taken together, our study revealed that m
6
A RNA methylation regulators might play a significant role in the initiation and progression of PRCC. The results might provide novel insight into exploration of m
6
A RNA modification in PRCC and provide essential guidance for therapeutic strategies.
Background
The tumor microenvironment (TME) plays a critical role in tumorigenesis, development, and therapeutic efficacy. Major advances have been achieved in the treatment of various cancers ...through immunotherapy. Nevertheless, only a minority of patients have positive responses to immunotherapy, which is partly due to conditions of the immunosuppressive microenvironment. Therefore, it is essential to identify prognostic biomarkers that reflect heterogeneous landscapes of the TME.
Methods and materials
Based upon the ESTIMATE algorithm, we evaluated the infiltrating levels of immune and stromal components derived from patients afflicted by various types of cancer from The Cancer Genome Atlas database (TCGA). According to respective patient immune and stromal scores, we categorized cases into high‐ and low‐scoring subgroups for each cancer type to explore associations between TME and patient prognosis. Gene Set Enrichment Analyses (GSEA) were conducted and genes enriched in IFNγ response signaling pathway were selected to facilitate establishment of a risk model for predicting overall survival (OS). Furthermore, we investigated the associations between the prognostic signature and tumor immune infiltration landscape by using CIBERSORT algorithm and TIMER database.
Results
Among the cancers assessed, the immune scores for skin cutaneous melanoma (SKCM) were the most significantly correlated with patients' survival time (P < .0001). We identified and validated a five‐IFNγ response‐related gene signature (UBE2L6, PARP14, IFIH1, IRF2, and GBP4), which was closely correlated with the prognosis for SKCM afflicted patients. Multivariate Cox regression analysis indicated that this risk model was an independent prognostic factor for SKCM. Tumor‐infiltrating lymphocytes and specific immune checkpoint molecules had notably differential levels of expression in high‐ compared to low‐risk samples.
Conclusion
In this study, we established a novel five‐IFNγ response‐related gene signature that provided a better and increasingly comprehensive understanding of tumor immune landscape, and which demonstrated good performance in predicting outcomes for patients afflicted by SKCM.
We established an effective five‐IFNγ response‐related gene‐based risk score, which has potential to be a novel prognostic signature and may provide insight into tumor immune microenvironment of cutaneous melanoma.
Preeclampsia is a pregnancy-induced hypertensive disorder that causes substantial maternal and fetal morbidity and mortality. Despite being a leading cause of maternal death and a major contributor ...to maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are poorly understood. Recent studies indicate that women with preeclampsia have autoantibodies that activate the angiotensin receptor, AT1, and that autoantibody-mediated receptor activation contributes to pathophysiology associated with preeclampsia. The research reviewed here raises the intriguing possibility that preeclampsia may be a pregnancy-induced autoimmune disease.
Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy. Elevated circulating endothelin-1 (ET-1) is associated with the disease. However the molecular basis of increased ET-1 ...production and its role in PE are unknown. This study aimed to investigate the causative factors, pathological role of elevated ET-1 production in PE, and the underlying mechanisms. In this study, we found that IgG from women with PE, in contrast to IgG from normotensive pregnant women, induced preproET-1 mRNA expression via angiotensin II type 1 receptor activation in kidneys and placentas in pregnant mice. The ET-A receptor-specific antagonist BQ123 significantly attenuated autoantibody-induced hypertension, proteinuria, and renal damage in pregnant mice, demonstrating that autoantibody-induced ET-1 production contributes to pathophysiology. Mechanistically, we discovered that IL-6 functioned downstream of TNF-α signaling, contributing to increased ET-1 production in pregnant mice. IL-6 blockade inhibited preeclamptic features in autoantibody-injected pregnant mice. Extending the data to human studies, we found that IL-6 was a key cytokine underlying ET-1 induction mediated by IgG from women with PE in human placental villous explants and that endothelial cells are a key source of ET-1. Overall, we provide human and mouse studies showing that angiotensin II type I receptor-agonistic autoantibody is a novel causative factor responsible for elevated ET-1 production and that increased TNF-α/IL-6 signaling is a key mechanism underlying increased ET-1 production and subsequent maternal features. Significantly, our findings revealed novel factors and signaling cascades involved in ET-1 production, subsequent disease symptom development, and possible therapeutic intervention in the management of PE.
•A refined finite element model of CRTS-II ballastless track is established to investigate the damage initiation and evolution of the wide and narrow joint.•The joint damage initiation and evolution ...under complexly extreme temperature load are analyzed.•Both the influence of joint damages and interface conditions on the track upper-arch mechanism are investigated under extreme temperature.•The results can provide valuable references for further research on interlayer debonding and slab arching repairment maintenance.
Joint damage has been a severe problem for the longitudinal CRTS-II type ballastless track, which affects vertical stability of the slab track significantly and threatens operation safety of the highspeed railway potentially. This paper presents a refined and detailed finite element model of the CRTS-II track to investigate the damage initiation and evolution of the wide and narrow joint, a pivotal part of the longitudinal CRTS-II track. In detail, a bilinear cohesion model is introduced to simulate the interfacial interaction accurately. And a concrete damage plasticity model is utilized to model the initiation and propagation of the joint crack for comprehensive analysis. The refined model analyzes the joint damage initiation and evolution under complexly extreme temperature load. Then, the influence of joint damages and interface conditions on the slab track upper-arch mechanism are investigated. The results show that tensile damage causes initial cracks inside the narrow joint, then the increase of compressive damage is the leading cause of the final failure of the narrow joint concrete. And the poor quality of concrete tends to cause the wide and narrow joint to be entirely crushed, while the high quality above C30 may cause joint damage intensively, leading to joint concrete fall-block. In addition, the upper-arch on the track slab increases linearly with the joint damage degree. With the interfacial tangential shear strength changing from 0.01 MPa to 1.5 MPa, the maximum arch height of the slab reduces by 4.5 mm.
Preeclampsia is a prevalent life-threatening hypertensive disorder of pregnancy for which the pathophysiology remains largely undefined. Recently, a circulating maternal autoantibody, the angiotensin ...II type I (AT1) receptor agonistic autoantibody (AA), has emerged as a contributor to disease features. Increased circulating maternal tumor necrosis factor α (TNF-α) is also associated with the disease; however, it is unknown whether this factor directly contributes to preeclamptic symptoms. Here we report that this autoantibody increases the proinflammatory cytokine TNF-α in the circulation of AT1-AA–injected pregnant mice but not in nonpregnant mice. Coinjection of AT1-AA with a TNF-α neutralizing antibody reduced cytokine availability in AT1-AA–injected pregnant mice. Moreover, TNF-α blockade in AT1-AA–injected pregnant mice significantly attenuated the key features of preeclampsia. Autoantibody-induced hypertension was reduced from 131±4 to 110±4 mm Hg, and proteinuria was reduced from 212±25 to 155±23 μg of albumin per milligram of creatinine (both P<0.05). Injection of AT1-AA increased the serum levels of circulating soluble fms-like tyrosine kinase 1 and soluble endoglin (34.1±5.1, 2.4±0.3 ng/mL, respectively) and coinjection with the TNF-α blocker significantly reduced their levels (21.7±3.4 and 1.2±0.4 ng/mL, respectively). Renal damage and placental abnormalities were also decreased by TNF-α blockade. Lastly, the elevated circulating TNF-α in preeclamptic patients is significantly correlated with the AT1-AA bioactivity in our patient cohort. Similarly, the autoantibody, through AT1 receptor–mediated TNF-α induction, contributed to increased soluble fms-like tyrosine kinase 1, soluble endoglin secretion, and increased apoptosis in cultured human villous explants. Overall, AT1-AA is a novel candidate that induces TNF-α, a cytokine that may play an important pathogenic role in preeclampsia.
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