The signal pathways and treatment of cytokine storm in COVID-19

The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It has affected a significant proportion of the global population both physically and mentally, and destroyed businesses and societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation of monocytes and macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, and especially, cytokine storm (CS). The CS is characterized by hyperproduction of an array of pro-inflammatory cytokines and is closely associated with poor prognosis. These excessively secreted pro-inflammatory cytokines initiate different inflammatory signaling pathways via their receptors on immune and tissue cells, resulting in complicated medical symptoms including fever, capillary leak syndrome, disseminated intravascular coagulation, acute respiratory distress syndrome, and multiorgan failure, ultimately leading to death in the most severe cases. Therefore, it is clinically important to understand the initiation and signaling pathways of CS to develop more effective treatment strategies for COVID-19. Herein, we discuss the latest developments in the immunopathological characteristics of COVID-19 and focus on CS including the current research status of the different cytokines involved. We also discuss the induction, function, downstream signaling, and existing and potential interventions for targeting these cytokines or related signal pathways. We believe that a comprehensive understanding of CS in COVID-19 will help to develop better strategies to effectively control immunopathology in this disease and other infectious and inflammatory diseases

Predicting Intracerebral Hemorrhage Patients’ Length-of-Stay Probability Distribution Based on Demographic, Clinical, Admission Diagnosis, and Surgery Information

The vast majority of patients with intracerebral hemorrhage (ICH) suffer from long and uncertain length of stay (LOS). The aim of our study was to provide decision support for discharge and admission plans by predicting ICH patients’ LOS probability distribution. The demographics, clinical predictors, admission diagnosis, and surgery information from 3,600 ICH patients were used in this study. We used univariable Cox analysis, multivariable Cox analysis, Cox-variable of importance (Cox-VIMP) analysis, and an intersection analysis to select predictors and used random survival forests (RSF)—a method in survival analysis—to predict LOS probability distribution. The Cox-VIMP method constructed by us effectively selected significant correlation predictors. The Cox-VIMP RSF model can improve prediction performance and is significantly different from the other models. The Cox-VIMP can contribute to the screening of predictors, and the RSF model can be established through those predictors to predict the probability distribution of LOS in each patient

Investigation of Electrochemical Performance and Gas Swelling Behavior on Li4Ti5O12/Activated Carbon Lithium-Ion Capacitor with Acetonitrile-Based and Ester-Based Electrolytes

Lithium-ion capacitors (LICs) have gained significant attention due to the combination on the advantages of electric double-layer capacitors (EDLCs) and lithium-ion batteries (LIBs). Herein, the LIC pouch cell was fabricated by an activated carbon (AC) cathode and a Li4Ti5O12 (LTO) anode. Two organic electrolytes (1 mol L−1 LiBF4/acetonitrile (AN) and 1 mol L−1 LiPF6/ ethylene carbonate (EC) + ethyl methyl carbonate (EMC) + dimethyl carbonate (DMC)) were chosen and the gas swelling behavior was studied. Compared with the ester-based LIC, the AN-based LIC displays higher energy density of 13.31 Wh kg−1 at 11.4 W kg−1 and even provides a value of 9.1 Wh kg−1 at 1075 W kg−1. Because of the lower DC Resistance of 0.761 mΩ, the maximum power density of the AN-based LIC reaches 12.5 kW kg−1. The AN-based LIC delivers good stability with an energy retention of 88.3% after 900 cycles. It is discovered that the swelling behavior of AN-based LICs is more serious and the major component is H2. The difference of swelling behavior among the LICs, lithium nickel cobalt manganese oxide (NCM)/LTO LIB and AC/AC EDLC is proposed to be caused by the AC electrode and the interfacial reaction of LTO

Optimal massive-MIMO-aided clustered base-station coordination

A large-scale clustered massive MIMO network is proposed for improving the spectral efficiency of the nextgeneration wireless infrastructure by maximizing its sum-rate. Our solution combines the advantages of the centralized processing architecture and massive MIMO. Explicitly, the network is divided into multiple clusters; each cluster is handled by a centralized processing unit, which connects to a certain number of massive MIMO-aided BSs, where only limited information is exchanged among the clusters; each user of a cluster can be served by several nearby BSs in a user-centric way. We analyze the maximum sum-rate of the network with multiple antennas at BSs and UEs, relying on the optimal transmit precoder matrix of each BS configured for each user, and on the optimal frequency-domain power sharing scheme of each cluster. The optimizations are conceived for multiple coordination schemes that were widely studied in literature, namely the coherent-joint-transmission (CJT) scheme, the noncoherent- joint-transmission (NCJT) scheme and the coordinatedbeamfoming/scheduling (CBF/CS) scheme. Our simulations show that the optimal CJT achieves 2.2 – 4.5 times higher average sumrate than its non-cooperative massive MIMO network counterpart, while the optimal NCJT and the optimal CBF/CS achieve at most a factor 1.3 average sum-rate gain. The popular signalto-leakage-and-noise-ratio (SLNR) scheme is also extended to the multi-antenna UE scenario and achieves a factor 1.1 – 1.2 gain

Systematic identification of potential key microRNAs and circRNAs in the dorsal root ganglia of mice with sciatic nerve injury

BackgroundNeuropathic pain (NeP) is a pathological condition arising from a lesion or disease affecting the somatosensory system. Accumulating evidence has shown that circular RNAs (circRNAs) exert critical functions in neurodegenerative diseases by sponging microRNAs (miRNAs). However, the functions and regulatory mechanisms of circRNAs as competitive endogenous RNAs (ceRNAs) in NeP remain to be determined.MethodsThe sequencing dataset GSE96051 was obtained from the public Gene Expression Omnibus (GEO) database. First, we conducted a comparison of gene expression profiles in the L3/L4 dorsal root ganglion (DRG) of sciatic nerve transection (SNT) mice (n = 5) and uninjured mice (Control) (n = 4) to define the differentially expressed genes (DEGs). Then, critical hub genes were screened by exploring protein–protein interaction (PPI) networks with Cytoscape software, and the miRNAs bound to them were predicted and selected and then validated by qRT-PCR. Furthermore, key circRNAs were predicted and filtered, and the network of circRNA-miRNA-mRNA in NeP was constructed.ResultsA total of 421 DEGs were identified, including 332 upregulated genes and 89 downregulated genes. Ten hub genes, including IL6, Jun, Cd44, Timp1, and Csf1, were identified. Two miRNAs, mmu-miR-181a-5p and mmu-miR-223-3p, were preliminarily verified as key regulators of NeP development. In addition, circARHGAP5 and circLPHN3 were identified as key circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these differentially expressed mRNAs and targeting miRNAs were involved in signal transduction, positive regulation of receptor-mediated endocytosis and regulation of neuronal synaptic plasticity. These findings have useful implications for the exploration of new mechanisms and therapeutic targets for NeP.ConclusionThese newly identified miRNAs and circRNAs in networks reveal potential diagnostic or therapeutic targets for NeP

Microglial BDNF, PI3K, and p-ERK in the Spinal Cord Are Suppressed by Pulsed Radiofrequency on Dorsal Root Ganglion to Ease SNI-Induced Neuropathic Pain in Rats

Background. Pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG) has been applied to alleviate neuropathic pain effectively, yet the mechanisms underlying pain reduction owing to this treatment are not clarified completely. The activated microglia, brain-derived neurotrophic factor (BDNF), phosphatidylinositol 3-kinase (PI3K), and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal cord were demonstrated to be involved in developing neuropathic pain. Also, it has been just known that PRF on DRG inhibits the microglial activation in nerve injury rats. Here, we aim to investigate whether PRF treatment could regulate the levels of BDNF, PI3K, and p-ERK in the spinal cord of rats with spared nerve injury (SNI) via suppressing the spinal microglia activation to ease neuropathic pain. Methods. The rats with SNI were intrathecally treated with minocycline (specific microglia inhibitor) or same volume of dimethyl sulfoxide once daily, beginning from 1 h before nerve transection to 7 days. PRF was applied adjacent to the L4-L5 DRG of rats with SNI at 45 V for 6 min on the seventh postoperative day, whereas the free-PRF rats were treated without PRF. The withdrawal thresholds were studied, and the spinal levels of ionized calcium-binding adapter molecule 1 (Iba1), BDNF, PI3K, and p-ERK were calculated by western blot analysis, reverse transcription-polymerase chain reaction, and immunofluorescence. Results. The paw withdrawal mechanical threshold and paw withdrawal thermal latency decreased in the ipsilateral hind paws after SNI, and the spinal levels of Iba1, BDNF, PI3K, and p-ERK increased on day 21 after SNI compared with baseline (P<0.01). An intrathecal injection of minocycline led to the reversal of SNI-induced allodynia and increase in levels of Iba1, BDNF, PI3K, and p-ERK. Withdrawal thresholds recovered partially after a single PRF treatment for 14 days, and SNI-induced microglia hyperactivity, BDNF upregulation, and PI3K and ERK phosphorylation in the spinal cord reduced on D14 due to the PRF procedure. Conclusion. Microglial BDNF, PI3K, and p-ERK in the spinal cord are suppressed by the therapy of PRF on DRG to ease SNI-induced neuropathic pain in rats

High-voltage pulsed radiofrequency improves ultrastructure of DRG and enhances spinal microglial autophagy to ameliorate neuropathic pain induced by SNI

Abstract Neuropathic pain (NeP) is intractable for which many therapies are ineffective. High-voltage pulsed radiofrequency (HVPRF) on dorsal root ganglion (DRG) is considered an effective treatment for NeP. The aim of this study is to explore the therapeutic voltage for the optimal efficacy of PRF and the underlying mechanisms. The radiofrequency electrode was placed close to the L5 DRG of rats with spared nerve injury (SNI) and emitted current by the corresponding voltage in different groups. Four different voltages (45 V, 65 V, 85 V, and 100 V) of PRF on DRG significantly alleviated the SNI-induced NeP, reduced the levels of activating transcription factor 3 (ATF3) in DRG, improved the ultrastructure of DRG, and promoted autophagy in spinal microglia to varying degrees and partially reversed the increased expression of TNF-α and the reduced expression of IL-10 in spinal cord dorsal horn (SCDH). The beneficial effect of 85V-PRF was superior to those of other three PRF treatments. The underlying mechanisms may be related to repairing the DRG damage and improving the DRG ultrastructure while regulating spinal microglial autophagy and thereby alleviating neuroinflammation

Tribocorrosion performance of nano-layered coating in artificial seawater

Tribocorrosion performance of nano-layered coating in artificial seawate

Aggregation Behaviors of PEO-PPO-ph-PPO-PEO and PPO-PEO-ph-PEO-PPO at an Air/Water Interface: Experimental Study and Molecular Dynamics Simulation

The block polyethers PEO-PPO-ph-PPO-PEO (BPE) and PPO-PEO-ph-PEO-PPO (BEP) are synthesized by anionic polymerization using bisphenol A as initiator. Compared with Pluronic P123, the aggregation behaviors of BPE and BEP at an air/water interface are investigated by the surface tension and dilational viscoelasticity. The molecular construction can influence the efficiency and effectiveness of block polyethers in decreasing surface tension. BPE has the most efficient ability to decrease surface tension of water among the three block polyethers. The maximum surface excess concentration (Γ_max) of BPE is larger than that of BEP or P123. Moreover, the dilational modulus of BPE is almost the same as that of P123, but much larger than that of BEP. The molecular dynamics simulation provides the conformational variations of block polyethers at the air/water interface