PL-TARMI: A deep learning framework for pixel-level traffic crash risk map inference.

A citywide traffic crash risk map is of great significance for preventing future traffic crashes. However, the fine-grained geographic traffic crash risk inference is still a challenging task, mainly due to the complex road network structure, human behavior and high data requirements. In this work, we propose a deep-learning framework PL-TARMI, which leverages easily accessible data to achieve accurate fine-grained traffic crash risk map inference. Specifically, we integrate the satellite image and road network image, combine with other accessible data (e.g., point of interest distribution, human mobility data, traffic data, etc.) as input, and finally obtain the pixel-level traffic crash risk map, which could provide more reasonable traffic crash prevention guidance with a lower cost. Extensive experiments on real-world datasets demonstrate the effectiveness of PL-TARMI.

Study on endogenous inhibitors against PD-L1: cAMP as a potential candidate.

The discovery of new anti-cancer drugs targeting the PD-1/PD-L1 pathway has been a research hotspot in recent years. In this study, biological affinity ultrafiltration (BAU), UPLC-HRMS, molecular dynamic (MD) simulations and molecular docking methods were applied to search for endogenous active compounds that can inhibit the binding of PD-L1 to PD-1. We screened dozens of potential cancer related endogenous compounds. Surprisingly, cyclic adenosine monophosphate (cAMP) was found to have a direct inhibitory effect on the PD-1/PD-L1 binding with an in vitro IC50 value of about 36.4 ± 9.3 µM determined by homogeneous time-resolved fluorescence (HTRF) assay. cAMP could recover the proliferation of Jurkat T cells co-cultured with DU-145 cells and may suppress PD-L1 expression of DU-145 cells. cAMP was demonstrated to bind and induce PD-L1 dimerization by FRET assay, and also predicted by MD simulations and molecular docking. The finding of cAMP as a potential inhibitor directly targeting the PD-1/PD-L1 interaction could advance our understanding of the activity of endogenous compounds regulating PD-L1.

Disulfiram reduces the severity of mouse acute pancreatitis by inhibiting RIPK1-dependent acinar cell necrosis.

Acute pancreatitis (AP) is a frequent abdominal inflammatory disease. Despite the high morbidity and mortality, the management of AP remains unsatisfactory. Disulfiram (DSF) is an FDA-proved drug with potential therapeutic effects on inflammatory diseases. In this study, we aim to investigate the effect of DSF on pancreatic acinar cell necrosis, and to explore the underlying mechanisms. Cell necrosis was induced by sodium taurocholate or caerulein, AP mice model was induced by nine hourly injections of caerulein. Network pharmacology, molecular docking, and molecular dynamics simulation were used to explore the potential targets of DSF in protecting against cell necrosis. The results indicated that DSF significantly inhibited acinar cell necrosis as evidenced by a decreased ratio of necrotic cells in the pancreas. Network pharmacology, molecular docking, and molecular dynamics simulation identified RIPK1 as a potent target of DSF in protecting against acinar cell necrosis. qRT-PCR analysis revealed that DSF decreased the mRNA levels of RIPK1 in freshly isolated pancreatic acinar cells and the pancreas of AP mice. Western blot showed that DSF treatment decreased the expressions of RIPK1 and MLKL proteins. Moreover, DSF inhibited NF-κB activation in acini. It also decreased the protein expression of TLR4 and the formation of neutrophils extracellular traps (NETs) induced by damage-associated molecular patterns released by necrotic acinar cells. Collectively, DSF could ameliorate the severity of mouse acute pancreatitis by inhibiting RIPK-dependent acinar cell necrosis and the following formation of NETs.

Ruthenium red attenuates acute pancreatitis by inhibiting MCU and improving mitochondrial function.

Acute pancreatitis (AP) is a common inflammatory disease of the digestive system. Mitochondrial calcium uniporter (MCU) mediates mitochondrial uptake of Ca2+ and plays an important role in calcium homeostasis. However, it is undefined whether AP can be relieved by inhibiting MCU. This study aimed to study the therapeutic potential of Ruthenium red (RuR), a MCU inhibitor, in AP mice model and primary acinar cells. Cell injury and AP mice model was induced by caerulein. RuR alleviated CER-AP evidenced by reduced serum lipase, TNF-α, and pancreatic MPO levels, less severe pancreatic pathology damage, and decreased inflammatory cell infiltration. In freshly isolated pancreatic acinar cells, RuR diminished cell necrosis with effect on suppressing the expression of MCU. RuR also decreased levels of cytosolic calcium and ROS, preventing mitochondrial membrane potential loss, ATP depletion and MPTP opening. The present findings indicate that inhibit MCU by RuR has a beneficial effect in AP by preventing calcium overload, mitochondrial dysfunction, and cell necrosis.

The optimal duration of triple antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome or undergoing percutaneous coronary intervention: A network meta-analysis of randomized clinical trials.

BACKGROUND: Triple antithrombotic therapy (TAT) consisting of anticoagulant and dual antiplatelet agents is a core treatment for prevention of ischemic events in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing post-percutaneous coronary intervention (PCI), however, due to bleeding risks, the optimal duration of TAT is unclear. METHODS: We searched the database and conducted a network meta-analysis of randomized controlled trials (RCTs) to determine the optimal duration of TAT for patients with AF and ACS or undergoing PCI by comparing the probability of ischemic and bleeding outcomes for four different TAT durations. RESULTS: After analyzing data from 12,329 patients, we determined that short-term TAT is advantageous to varying degrees for reducing bleeding events. While long-term TAT has a lower stent thrombosis risk than short-term TAT, the four strategies have comparable outcomes for major adverse cardiovascular events (MACE), stroke, all-cause death, and myocardial infarction events. Based on Surface Under the Cumulative Ranking (SUCRA) values, no treatment duration has an absolute advantage for reducing these ischemic events. CONCLUSION: Long-term TAT may be reasonable for patients at a high risk for stent thrombosis, but short-term TAT is associated with fewer bleeding complications, and there are no significant differences in most ischemic events across treatment durations. Overall, our results indicate that short-term TAT should be the default strategy unless there is a high risk of stent thrombosis that warrants appropriate prolongation of TAT duration.

Affinity ultrafiltration and UPLC-HR-Orbitrap-MS based screening of thrombin-targeted small molecules with anticoagulation activity from Poecilobdella manillensis.

This study aims to screen potential anticoagulant components from leeches, a representative animal-sourced traditional Chinese medicine using thrombin (THR)-targeted ultrafiltration combined with ultrahigh performance liquid chromatography and high-resolution Orbitrap mass spectrometry (UPLC-HR-Orbitrap-MS). As a result, five small molecules in leech extract were discovered to interact with THR for the first time. Among them, two new compounds were isolated and their structures were identified by IR, HR-MS and NMR data. Furthermore, their THR inhibitory activity was confirmed with IC50 values of 4.74 and 8.31 µM, respectively. In addition, molecular docking analysis showed that the active (catalytic) site of THR might be the possible binding site of the two hits. Finally, reverse screening analysis indicated that LTA4-H, ACE and ALOX5AP were potential anticoagulant targets of the two new compounds. This study will broaden our understanding of the medicinal substance basis in leeches and further contribute to the discovery and development of clinical anticoagulant drugs from leeches.

A novel thrombin inhibitory peptide discovered from leech using affinity chromatography combined with ultra-high performance liquid chromatography-high resolution mass spectroscopy.

Thrombin (THR) inhibitors play an important role in the treatment of thrombotic diseases. This study established a THR-based bio-specific extraction coupled with affinity chromatography and ultra-high performance liquid chromatography-high resolution mass spectroscopy (UPLC-HR-MS) analysis method to screen and identify THR ligands in Leech. After evaluating the reliability of the screening method using positive control drug (hirudin), it was successfully used to screen the potential active constituents in leech. And a comprehensive analysis of the peptides in leech elution was performed by UPLC-HR-MS, a total of 34 peptides were identified. At the same time, anti-THR activity was explored and inferred by searching databases and published literature. As a result, six peptides were discovered to be potential active compounds in leech. Further, the six peptides were synthesized and in vitro enzymatic activity assay was performed. Finally, SYELPDGQVITIGNER was screened as an anti-THR peptide with an IC50 value of 255.75 µM and it was discovered for the first time from Whitmania pigra Whitman and Hirudo nipponica Whitman. The molecular docking study showed that THR inhibitory activity of the polypeptide was mainly attributed to the hydrogen bond interactions, van der Waals forces and electrostatic interactions interaction between polypeptide and THR. These results suggest that the polypeptide is a potential natural THR inhibitor that can be used as anticoagulant.

Inter-urban mobility via cellular position tracking in the southeast Songliao Basin, Northeast China.

Position tracking using cellular phones can provide fine-grained traveling data between and within cities on hourly and daily scales, giving us a feasible way to explore human mobility. However, such fine-grained data are traditionally owned by private companies and is extremely rare to be publicly available even for one city. Here, we present, to the best of our knowledge, the largest inter-city movement dataset using cellular phone logs. Specifically, our data set captures 3-million cellular devices and includes 70 million movements. These movements are measured at hourly intervals and span a week-long duration. Our measurements are from the southeast Sangliao Basin, Northeast China, which span three cities and one country with a collective population of 8 million people. The dynamic, weighted and directed mobility network of inter-urban divisions is released in simple formats, as well as divisions' GPS coordinates to motivate studies of human interactions within and between cities.

The temporal geographically-explicit network of public transport in Changchun City, Northeast China.

The vehicle trajectory data is a feasible way for us to understand and reveal urban traffic conditions and human mobility. Therefore, it is extremely valuable to have a fine-grained picture of large-scale vehicle trajectory data, particularly in two different modes, taxis and buses, over the same period at an urban scale. This paper integrates the trajectory data of approximately 7,000 taxis and 1,500 buses in Changchun City, China and accesses the temporal geographically-explicit network of public transport via sequential snapshots of vehicle trajectory data every 30 seconds of the first week in March 2018. In order to reveal urban traffic conditions and human mobility, we construct two-layer urban traffic network (UTN) between these two different transport modes, take crossings as nodes and roads as edges weighted by the volume or average speed of vehicles in each hour. We released this temporal geographically-explicit network of public transport and the dynamics, weighted and directed UTN in simple formats for easy access.

The temporal network of mobile phone users in Changchun Municipality, Northeast China.

Mobile data are a feasible way for us to understand and reveal the feature of human mobility. However, it is extremely hard to have a fine-grained picture of large-scale mobility data, in particular at an urban scale. Here, we present a large-scale dataset of 2-million mobile phone users with time-varying locations, denoted as the temporal network of individuals, conducted by an open-data program in Changchun Municipality. To reveal human mobility across locations, we further construct the aggregated mobility network for each day by taking cellular base stations as nodes coupled by edges weighted by the total number of users' movements between pairs of nodes. The resulting temporal network of mobile phone users and the dynamic, weighted and directed mobility network are released in simple formats for easy access to motivating research using this new and extensive data of human mobility.

Polysaccharides from Dendrobium officinale inhibit bleomycin-induced pulmonary fibrosis via the TGFß1-Smad2/3 axis.

Polysaccharides from Dendrobium officinale (PDO) have been found to elicit significant benefits for patients with fibrotic diseases. However, there are no reports on treatment of idiopathic pulmonary fibrosis (IPF) using PDO. The aim of this paper was to investigate the therapeutic effects of PDO on IPF and its underlying mechanisms. Our data showed that PDO significantly ameliorated indices for both pulmonary inflammation and fibrosis in a bleomycin (BLM)-induced pulmonary fibrosis model in rats, which was associated with inactivation of transforming growth factor ß1 (TGFß1)-Smad2/3 signaling pathway. Moreover, PDO effectively blocked TGFß1-induced transformation of rat alveolar epithelial type II cells into myofibroblasts, with the inhibition of total Smad2/3, pSmad2/3, collagen I and fibronectin protein expression in a dose-dependent manner in vitro. Therefore, PDO may represent as a promising candidate biomacromolecule drug for the safe and effective therapy of IPF.