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How to deal with the ever more complex religious relationships is not only a significant issue for Chinese central government and the Communist Party but also a cutting-edge topic for the religious academy at home and abroad. Based on the review of the latest internationally acknowledged four theoretical orientations, namely religious market model, religious ecological model, religious compatibilism, and religious praxism, this article proposes an innovated framework, positive orientating theory of Chinese religious relations. The author intends to explore more active thoughts on theories and policies that would particularly reflect on and align with the typical characteristics of religious relationships in Chinese context.Contribution: Based on the review of the latest internationally acknowledged four theoretical orientations, namely religious market model, religious ecological model, religious compatibilism, and religious praxism, this article proposes an innovated framework, positive orientating theory of Chinese religious relations.

The recent success of PD-1 and PD-L1 blockade in cancer therapy illustrates the important role of the PD-1/PD-L1 pathway in the regulation of antitumor immune responses. However, signaling regulated by the PD-1/PD-L pathway is also associated with substantial inflammatory effects that can resemble those in autoimmune responses, chronic infection, and sepsis, consistent with the role of this pathway in balancing protective immunity and immunopathology, as well as in homeostasis and tolerance. Targeting PD-1/PD-L1 to treat cancer has shown benefits in many patients, suggesting a promising opportunity to target this pathway in autoimmune and inflammatory disorders. Here, we systematically evaluate the diverse biological functions of the PD-1/PD-L pathway in immune-mediated diseases and the relevant mechanisms that control these immune reactions.

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the characteristic pathological changes of DN and Tervaert pathological classification, which divides DN into four classifications according to glomerular lesions, along with a separate scoring system for tubular, interstitial, and vascular lesions. Given the heterogeneity of the renal lesions and the complex mechanism underlying diabetic nephropathy, Tervaert classification has both significance and controversies in the guidance of diagnosis and prognosis. Applications and evaluations using Tervaert classification and indications for renal biopsy are summarized in this review according to recent studies. Meanwhile, differential diagnosis with another nodular glomerulopathy and the situation that a typical DN superimposed with a nondiabetic renal disease (NDRD) are discussed and concluded in this review.

Colonocyte metabolism shapes the microbiome. Metabolites are the main mediators of information exchange between intestine and microbial communities. Arachidonic acid (AA) is an essential polyunsaturated fatty acid and its role in colorectal cancer (CRC) remains unexplored. In this study, we show that AA feeding promotes tumor growth in AOM/DSS and intestinal specific Apc −/− mice via modulating the intestinal microecology of increased gram-negative bacteria. Delta-5 desaturase (FADS1), a rate-limiting enzyme, is upregulated in CRC and effectively mediates AA synthesis. Functionally, FADS1 regulates CRC tumor growth via high AA microenvironment-induced enriched gram-negative microbes. Elimination of gram-negative microbe abolishes FADS1 effect. Mechanistically, gram-negative microbes activate TLR4/MYD88 pathway in CRC cells that contributes FADS1-AA axis to metabolize to prostaglandin E2 (PGE2). Cumulatively, we report a potential cancer-promoting mechanism of FADS1-AA axis in CRC that converts raising synthesized AA to PGE2 via modulating the intestinal microecology of gram-negative. The role of arachidonic acid (AA) in colorectal cancer (CRC) is unclear. Here they show that FADS1-AA axis modulates the intestinal microecology by enriching gram-negative bacteria in CRC and that the altered microecology accelerates the conversion of AA to PGE2, promoting CRC tumorigenesis.

Background Lysyl oxidase-like 4 (LOXL4) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). However, the role of LOXL4 in HCC progression remains largely unclear. In this study, we investigated the clinical significance and biological involvement of LOXL4 in the progression of HCC. Methods LOXL4 expression was measured in HCC tissues and cell lines. Overexpression, shRNA-mediated knockdown, recombinant human LOXL4 (rhLOXL4), and deletion mutants were applied to study the function of LOXL4 in HCC. Exosomes derived from HCC cell lines were assessed for the ability to promote cancer progression in standard assays. The effects of LOXL4 on the FAK/Src pathway were examined by western blotting. Results LOXL4 was commonly upregulated in HCC tissues and predicted a poor prognosis. Elevated LOXL4 was associated with tumor differentiation, vascular invasion, and tumor-node-metastasis (TNM) stage. Overexpression of LOXL4 promoted, whereas knockdown of LOXL4 inhibited cell migration and invasion of HCC in vitro, and overexpressed LOXL4 promoted intrahepatic and pulmonary metastases of HCC in vivo. Most interestingly, we found that HCC-derived exosomes transferred LOXL4 between HCC cells, and intracellular but not extracellular LOXL4 promoted cell migration by activating the FAK/Src pathway dependent on its amine oxidase activity through a hydrogen peroxide-mediated mechanism. In addition, HCC-derived exosomes transferred LOXL4 to human umbilical vein endothelial cells (HUVECs) though a paracrine mechanism to promote angiogenesis. Conclusions Taken together, our data demonstrate a novel function of LOXL4 in tumor metastasis mediated by exosomes through regulation of the FAK/Src pathway and angiogenesis in HCC.

Pumps are one of the core components of drilling equipment, and their fault diagnosis is of great significance. The data-driven approach has made remarkable achievements in the field of pump fault diagnosis; however, most of them are easily affected by complex background conditions and usually suffer from data scarcity problems in real-industrial scenarios, which limit their application in practical engineering. To overcome the above shortcoming, a novel framework for a model named Hyperparameter Optimization Multiple-Signal Fusion Transfer Convolution Neural Network is proposed in this paper. A convolutional neural network model based on transfer learning is built to promote well-learned knowledge transfer over different background conditions, improve robustness, and generalize the model to cross-domain diagnosis tasks. The multi-signal fusion strategy is involved in capturing system state information for establishing the mapping relationship between the raw signal and fault pattern by integrating the multi-physical signal with the weight allocation protocol. The hyperparameter optimization method is explored in conjunction with the transfer-based model by integrating Grid Search with the Gradient Descent algorithm for further improvement of diagnosis performance. Results show that the proposed model can effectively realize the fault diagnosis of pumps under different background conditions, achieving 95% accuracy.

This study was a post hoc analysis of data from a retrospective cohort population. The purpose of this study was to analyze the predictive value of albumin for the short-term survival of patients with unplanned early readmission to the emergency department (ED). A total of 6,249 emergency patients were enrolled in this study, including 5,368 patients (85.49%) who had been admitted for the first time and 881 patients (14.51%) with unplanned early readmission to the ED; the data were from the clinical cohort data publicly released on the Dryad website. The patients were classified on the basis of the tertile of their albumin values. Kaplan‒Meier survival curve analysis, the log-rank test and a Cox proportional hazards model were used to analyze the associations between albumin levels and 30-day mortality risk in emergency patients. The dose‒response relationship between albumin and outcome was fitted by a restricted cubic spline (RCS). Sensitivity analysis was performed on the results of the difference test by creating a multivariate Cox regression model with the forward likelihood ratio (LR) method. The demographic characteristics and clinical indicators of patients in the ED differed according to the number of admissions. The median albumin level of patients admitted to the hospital for the first time was greater than that of patients who were readmitted (Z = -9.642, P < 0.001). The duration of patient hospitalization was used as the follow-up time. The median length of hospitalization was 2 days (range: 1-123 days); 328 patients died within 30 days, and the all-cause mortality rate of patients with unplanned early readmission was higher than that of first-time hospitalization patients (4.49% vs. 9.86%, [Formula: see text] =44.136, P < 0.001). Kaplan-Meier survival curve analysis revealed that albumin levels were associated with 30-day mortality in all patients, first-time admitted patients, and patients with unplanned early readmission (log-rank test, P < 0.001). The multivariate Cox regression model revealed that albumin was a significant factor only in all patients combined (HR 0.93, 95% CI 0.91-0.95, P < 0.001) and in first-time admitted patients (HR 0.92, 95% CI 0.89-0.94, P < 0.001) but not in patients with unplanned early readmission (HR 0.97, 95% CI 0.93-1.01, P = 0.121). The same result was obtained with a Cox regression model in which albumin was included as a categorical variable. Sensitivity analysis revealed that the results of multivariate Cox regression analysis were reliable. There was a specific correlation between albumin and the short-term outcome of emergency patients. Albumin levels are associated with short-term outcomes in patients admitted to the hospital for the first time, but its association with the outcomes of patients with unplanned early readmission to the ED is likely trivial.

Colorectal cancer (CRC) is one of the most prevalent cancers globally and is one of the leading causes of cancer-related deaths due to therapy resistance and metastasis. Understanding the mechanism underlying colorectal carcinogenesis is essential for the diagnosis and treatment of CRC. microRNAs (miRNAs) can act as either oncogenes or tumor suppressors in many cancers. A tumor suppressor role for miR-27b has recently been reported in neuroblastoma, while no information about miR-27b in CRC is available. In this study, we demonstrated that miR-27b expression is decreased in most CRC tissues and determined that overexpression of miR-27b represses CRC cell proliferation, colony formation and tumor growth in vitro and in vivo. We identified vascular endothelial growth factor C (VEGFC) as a novel target gene of miR-27b and determined that miR-27b functioned as an inhibitor of tumor progression and angiogenesis through targeting VEGFC in CRC. We further determined that DNA hypermethylation of miR-27b CpG islands decreases miR-27b expression. In summary, an anti-tumor role for miR-27b and its novel target VEGFC in vivo could lead to tumor necrosis and provide a rationale for developing miR-27b as a therapeutic agent.

Early mobilization has been proven to be an effective and safe intervention for preventing complications in mechanically ventilated patients; however, there is currently no unified definition of the optimal mobilization initiation time, hindering widespread clinical implementation. As clinicians are increasingly aware of the benefits of early mobilization, the definition of early mobilization is important. The purpose of this study was to evaluate the effects of different early mobilization initiation times on mechanically ventilated patients and rank these times for practical consideration. The Chinese Biomedical Literature Database, the Chinese Knowledge Infrastructure, Wanfang Data, PubMed, Cochrane Library, Web of Science, and Embase databases, along with grey literature and reference lists, were searched for randomized control trials (RCTs) that evaluated the effects of early mobilization for improving patient outcomes; databases were searched from inception to October 2018. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook (v5.1.0). Data were analyzed using Stata (v13.0) and Review Manager (v5.3.0). A total of 15 RCTs involving 1726 patients and seven mobilization initiation times (which were all compared to usual care) were included in our analysis. Network meta-analysis showed that mechanical ventilation for 48-72 h may be optimal to improve intensive care unit acquired weakness (ICU-AW) and reduce the duration of mechanical ventilation; however, there were no significant differences in length of ICU stay according to mobilization initiation time. The results of this study indicate that initiation of mobilization within 48-72 h of mechanical ventilation may be optimal for improving clinical outcomes for mechanically ventilated patients.

The mid-latitude ecological environment is highly vulnerable, and increasing hydroclimate variability poses a significant threat to it. However, the mechanisms driving this variability remain unclear due to short observational records and climate model biases. Here, we present a sub-millennial resolution precipitation record spanning the past ~5.7 million years (Myr), derived from a 300.8-meter fluvio-lacustrine sediment core in mid-latitude East Asia (northern China). Our results reveal a persistent influence of the westerly jet on mid-latitude precipitation since the Pliocene, as well as a marked reduction in mid-latitude precipitation variability alongside amplified low-latitude variability after ~3 million years ago (Ma). Based on idealized sensitivity simulations, we attribute the amplified mid-latitude precipitation variability before ~3 Ma to enhanced westerly jet waviness driven by Arctic warming. Given projected increases in jet waviness under future global warming, we predict more frequent hydroclimate extremes in mid-latitude regions.