Interactions of graphene with oxidants in a mixed atmosphere: synergistic effects of O2/H2O and O2/CO2 on gasification reactivity and kinetics.

The gasification of carbon with O2, CO2, and H2O oxidants plays an important role in several energy-based applications. As most of the industrial gasification processes are conducted under mixed-atmosphere conditions, the oxidation of carbon in binary oxidant mixtures becomes crucially important. Using reactive force-field (ReaxFF) potentials, extensive MD simulations were carried out on the oxidation behavior of graphene in mixed O2/H2O and O2/CO2 environments for a range of gas compositions and temperatures. A graphene sheet with a line defect comprising of eight and four-membered rings was used as the starting carbon structure. In addition to enhanced carbon gasification with oxygen additions, MD simulations showed synergistic interactions between different oxidants and their net influence on the overall reactivities. The gasification levels achieved under the binary system were higher than the linear combination of contributions from individual oxidants. The addition of ∼40% O2 in the binary mix was identified as the region with the highest reactivity during the initial stages of gasification. The oxidation reactions with oxygen were found to start instantaneously in the presence of H2O or CO2 instead of the usual initial delay. A very fast reaction kinetics was also observed in the initial stages in the presence of oxygen. Our results show that the gasification reactions under H2O and CO2 started at lower temperatures than O2 thereby creating a partially oxidized structure. Due to the presence of a large number of activation sites, very high rates of gasification were achieved with oxygen. These findings could help identify optimal oxidant compositions towards maximizing carbon gasification and minimizing CO2 emissions.

Electroacupuncture regulates gut microbiota to reduce depressive-like behavior in rats.

Background and objectives: Growing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to observe the effect of electroacupuncture (EA) on gut microbiota in rats that showed depressive-like behavior. Materials and methods: The rats were randomly divided into normal group, chronic unpredictable mild stress model (CUMS) group, CUMS + electroacupuncture (EA) group, and CUMS + sham-electroacupuncture (Sham) group. The CUMS+EA rats were treated with EA stimulation at bilateral Zusanli (ST36) and Tianshu (ST25) acupoints for 2 weeks (0.7 mA, 2/100 Hz, 30 min/day). The rats in the sham EA group were treated with the same conditions without inserting needles and electrical stimulation. Behavioral tests were conducted by forced swimming test (FST), open field test (OFT), and sucrose preference test (SPT) to assess depression-like behavior in rats. The relative abundance of intestinal bacteria in rat feces was detected by 16S rRNA analysis. The expression of calcitonin-gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SST), and adrenocorticotropic hormone (ACTH) in serum was detected by ELISA kit, and VIP, CGRP, and SST in the colon were detected by qRT-PCR and Western blot. Results: Chronic unpredictable mild stress model rats exhibited depressive-like behaviors and had differential abundance vs. control rats. CUMS significantly decreased the relative abundance of Bifidobacterium and Streptococcus at the genus level, CGRP in plasma (p < 0.05), and significantly increased the intestine propulsion rate, the mRNA and protein expression of VIP, SST, and mRNA in the colon, and ATCH in plasma (p < 0.05). EA rats with microbial profiles were distinct from CUMS rats. EA markedly reduced the depressive-like behaviors, significantly increased the intestine propulsion rate, the relative abundance of Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level, Bifidobacterium and Streptococcus at the genus level, and VIP and CGRP in plasma (p < 0.05), and significantly decreased Firmicutes, the ratio of Firmicutes to Bacteroidetes at the phylum level, ACTH and SST in plasma, and SST mRNA in the colon (p < 0.05). Conclusion: The antidepressant effect of EA at ST36 and ST25 is related to regulating intestinal flora and the neurotransmitter system. Our study suggests that EA contributes to the improvement of depression, and gut microbiota may be one of the mechanisms of EA effect.

Developments in Atomistic and Nano Structure Evolution Mechanisms of Molten Slag Using Atomistic Simulation Methods.

Molten slag has different properties depending on its composition. The relationship between its composition, structure, and properties has been the focus of attention in industrial manufacturing processes. This review describes the atomistic scale mechanisms by which oxides of different compositions affect the properties and structure of slag, and depicts the current state of research in the atomic simulation of molten slag. At present, the research on the macroscopic properties of molten slag mainly focuses on viscosity, free-running temperature, melting point, and desulphurization capacity. Regulating the composition has become the most direct and effective way to control slag properties. Analysis of the microevolution mechanism is the fundamental way to grasp the macroscopic properties. The microstructural evolution mechanism, especially at the atomic and nanoscale of molten slag, is reviewed from three aspects: basic oxides, acidic oxides, and amphoteric oxides. The evolution of macroscopic properties is analyzed in depth through the evolution of the atomic structure. Resolution of the macroscopic properties of molten slag by the atomic structure plays a crucial role in the development of fundamental theories of physicochemistry.

Kinetics formulation for Two-Dimensional Growth Behavior of Water/Ice Interface on Si Substrate.

Sublimation drying is used in the drying process of semiconductor device manufacturing. However, the solidification behavior mechanics of sublimation agents on substrates has not been clarified. Therefore, the properties of solidified films within substrate surfaces can become nonuniform, leading to their collapse. This study aimed to analyze the interface growth behavior during the cooling and solidification of a water/ice system as a basic case and to clarify the dynamic mechanism of the solidification behavior of liquid films on Si substrates. The solidification behavior of a water/ice system on Si substrates was captured on a video at different cooling rates. The recorded video was subjected to a digital image analysis to examine the crystal morphology and quantify the interface growth rate. The least-squares method with kinetic formulas was used to evaluate the feasibility of fitting the temperature variation to the interface growth rate. A visual examination of the morphology of interfacial growth revealed that it can be classified into four morphologies. The proposed kinetic equation describes the experimental results regarding the temperature dependence of the interfacial growth rate. Through image analysis, the interface growth rate of water and ice was quantified, and an evaluation formula was proposed.

Deep learning, geometric characterization and hydrodynamic modeling for assessing sewer defect impacts on urban flooding: A case study in Guangzhou, China.

Deep learning techniques have offered innovative and efficient tools for accurate and automated detection of sewer defects by leveraging large-scale sewer data and advanced feature learning algorithms. However, there has been a lack of thorough characterization of the geometric properties of segmented defects, let alone systematically calculate the severity level of sewer defects and quantitatively evaluate their impacts on flood conditions in hydrodynamic models. This study proposed a comprehensive framework and related metrics to accurately and automatically detect, segment, characterize, and evaluate the impacts of sewer defects on flooded nodes and volumes by integrating a DeepLabv3+-based segmentation technique, an automated geometric characterization and severity quantification module, and a GIS and SWMM-based hydrodynamic modeling. The results clearly showed in details where and how much the urban flooding was affected by the different defect types. The segmentation model achieved satisfactory detection performance, with mean pixel accuracy (MPA), mean intersection over union (MIoU), and frequency weighted intersection over union (FWIoU) of 0.99, 0.74 and 0.95, respectively. In terms of severity level quantification, there were 98%, 90%, 90% and 83% of predictions consistent with real conditions for falling off, obstacle, disjoint and leakage. It was shown that the number of surcharging manholes and total flood volume (TFV) were greatly affected by sewer defects, with over 16% increase in TFVs under all investigated rainfall events. The results addressed the impacts of sewer defects on urban flooding and demonstrated the powerful tools provided by the proposed framework for decision-making on sewer defect detection and management.

The evolution of atomistic structure and mechanical property of coke in the gasification process with CO2 and H2O at different temperatures: A ReaxFF molecular dynamics study.

CONTEXT: An atomistic coke carbon model was constructed to simulate the structural evolution in the gasification and stretching process. The coke model was placed in a box with different CO2/H2O content to investigate the evolution of the atomistic structure of coke during the gasification. It was found that different atmospheric concentrations had different effects on the structure and reaction sites of the coke model. The CO2 molecules tended to dissolve on the surface of coke and disrupt its surface structure, while H2O molecules were more likely to enter the coke model to disrupt the internal structure. For tensile simulation, it was found that CO2 and H2O had different effects on the tensile resistance of the coke model. Controlling the composition content of the reaction gas can effectively influence the tensile strength of the coke model. By revealing the behavior of coke model at the micro scale, it provides a theoretical basis for the industrial coke application process. METHODS: Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) was used to conduct the molecular dynamics using the reactive force field (ReaxFF). The atomistic model of coke carbon was constructed using the well-known annealing and quenching method, and its composition is determined according to the element analysis of industrial coke. The structural evolution in the gasification with CO2/H2O and the stretching process were analyzed in detail. Molecular dynamics simulations with reactive force field (ReaxFF-MD) were used to simulate the coke dissolution reaction under CO2/H2O atmosphere and the coke stretching process. The atmosphere ratio was modified to investigate the changes in coke structure under different atmosphere conditions. The Packmol software was used to place gas and coke models into the same box. During the reaction process, the Ovito software was used to perform corresponding visualization analysis on the changes in the atomic structure of coke.

Effect of Different sp2 Bond Contents on the Reactivity and Mechanical Properties of Coke Carbon: A ReaxFF Molecular Dynamics Study.

In this study, ReaxFF-MD was used to construct a large-molecule model of coke containing 3000 atoms, and the sp2 bond content of the model was controlled by changing the heating and cooling rates. The increase of the sp2 bond content led to a significant difference in the reactivity of coke. The presence of the sp2 bond caused the carbon atoms inside the coke to change into a circular structure, making it more difficult for the gaseous atoms to adsorb on the surface of the coke. It significantly reduced the gasification reaction rate of coke in the CO2 and H2O atmospheres. In the tensile simulation experiment, it was found that the stretching process of coke was mainly divided into three stages: an elastic stretching stage, a plastic stretching stage, and a model fracture stage. During the stretching process, the carbon ring structure would undergo a C-C bond fracture while generating carbon chains to resist stress. The results indicated that the presence of sp2 bonds can effectively reduce the phenomenon of excessive local stress on coke to improve its tensile resistance. The method developed in this paper may provide further ideas and platforms for the research on coke performance.

The Adsorption Mechanism of Hydrogen on FeO Crystal Surfaces: A Density Functional Theory Study.

The hydrogen-based direct reduction of iron ores is a disruptive routine used to mitigate the large amount of CO2 emissions produced by the steel industry. The reduction of iron oxides by H2 involves a variety of physicochemical phenomena from macroscopic to atomistic scales. Particularly at the atomistic scale, the underlying mechanisms of the interaction of hydrogen and iron oxides is not yet fully understood. In this study, density functional theory (DFT) was employed to investigate the adsorption behavior of hydrogen atoms and H2 on different crystal FeO surfaces to gain a fundamental understanding of the associated interfacial adsorption mechanisms. It was found that H2 molecules tend to be physically adsorbed on the top site of Fe atoms, while Fe atoms on the FeO surface act as active sites to catalyze H2 dissociation. The dissociated H atoms were found to prefer to be chemically bonded with surface O atoms. These results provide a new insight into the catalytic effect of the studied FeO surfaces, by showing that both Fe (catalytic site) and O (binding site) atoms contribute to the interaction between H2 and FeO surfaces.

BACE1 in PV interneuron tunes hippocampal CA1 local circuits and resets priming of fear memory extinction.

BACE1 is the rate-limiting enzyme for ß-amyloid (Aß) production and therefore is considered a prime drug target for treating Alzheimer's disease (AD). Nevertheless, the BACE1 inhibitors failed in clinical trials, even exhibiting cognitive worsening, implying that BACE1 may function in regulating cognition-relevant neural circuits. Here, we found that parvalbumin-positive inhibitory interneurons (PV INs) in hippocampal CA1 express BACE1 at a high level. We designed and developed a mouse strain with conditional knockout of BACE1 in PV neurons. The CA1 fast-spiking PV INs with BACE1 deletion exhibited an enhanced response of postsynaptic N-methyl-D-aspartate (NMDA) receptors to local stimulation on CA1 oriens, with average intrinsic electrical properties and fidelity in synaptic integration. Intriguingly, the BACE1 deletion reorganized the CA1 recurrent inhibitory motif assembled by the heterogeneous pyramidal neurons (PNs) and the adjacent fast-spiking PV INs from the superficial to the deep layer. Moreover, the conditional BACE1 deletion impaired the AMPARs-mediated excitatory transmission of deep CA1 PNs. Further rescue experiments confirmed that these phenotypes require the enzymatic activity of BACE1. Above all, the BACE1 deletion resets the priming of the fear memory extinction. Our findings suggest a neuron-specific working model of BACE1 in regulating learning and memory circuits. The study may provide a potential path of targeting BACE1 and NMDAR together to circumvent cognitive worsening due to a single application of BACE1 inhibitor in AD patients.

Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2.

Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 µM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 µM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

The Dynamic Nature of Graphene Active Sites in the H2O Gasification process: A ReaxFF and DFT Study.

CONTEXT: A steam-rich environment is a more promising application scenario for future coal-fired processes, while active sites are the key factor that determines the reactivity of carbonaceous fuels. The steam gasification process of carbon surfaces with different numbers of active sites (0, 12, 24, 36) was simulated using reactive molecular dynamics in the present study. The temperature for the decomposition of H2O and the gasification of carbon is determined using temperature-increasing simulation. The decomposition of H2O was influenced by two driving forces, thermodynamics and active sites on the carbon surface, which dominated the different reaction stages, leading to the observed segmentation phenomenon of the H2 production rate. The existence and number of initial active sites have a positive correlation with both two stages of the reaction, greatly reducing the activation energy. Residual OH groups play an important role in the gasification of carbon surfaces. The supply of OH groups through the cleavage of OH bonds in H2O is the rate-limiting step in the carbon gasification reaction. The adsorption preference at carbon defect sites was calculated using density functional theory. Two stable configurations (ether & semiquinone groups) can be formed with O atoms adsorbed on the carbon surface according to the number of active sites. This study will provide further insights into the tuning of active sites for advanced carbonaceous fuels or materials. METHODS: The large-scale atomic/molecule massively parallel simulator (LAMMPS) code combined with the reaction force-field method was used to carry out the ReaxFF molecular dynamics simulation, where the ReaxFF potentials were taken from Castro-Marcano, Weismiller and William. The initial configuration was built using Packmol, and the visualization of the calculation results was realized through Visual Molecular Dynamics (VMD). The timestep was set to 0.1 fs to detect the oxidation process with high precision. PWscf code in QUANTUM ESPRESSO (QE) package, was used to evaluate the relative stability of different possible intermediate configurations and the thermodynamic stability of gasification reactions. The projector augmented wave (PAW) and the generalized gradient approximation of Perdew-Burke-Ernzerhof (PBE-GGA) were adopted. Kinetic energy cutoffs of 50 Ry and 600 Ry, and a uniform mesh of 4 × 4 × 1 k-points were used.

Comprehensive RNA expression profile analysis of γδ T cells from peripheral blood and decidual tissues in normal pregnancy (NP) donors and patients with recurrent pregnancy loss (RPL).

Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication. The loss of immune tolerance has been proposed in the pathogenesis of RPL, however, the role of γδ T cells in RPL is still controversial. In this study, the gene expression patterns of circulated and decidual tissue-resident γδ T cells from normal pregnancy donors and patients with RPL were analyzed by SMART-seq. We demonstrate that the transcriptional expression profile of different subsets of γδ T cells in peripheral blood and decidual tissue is strikingly different. Vδ2 γδ T cells, as the major cytotoxic subset, are found to be enriched considerably, and the potential cytotoxicity of this subset is further enhanced in the decidua of RPL patients may be due to detrimental ROS reduction, enhanced metabolic activity, downregulation of immunosuppressive molecules expression in resident γδ T cells. Time-series Expression Miner (STEM) analysis of transcriptome indicates complex changes in gene expression in decidual γδ T cells over time from NP and RPL patients. Taken together, our work identifies high heterogeneity of gene signature in γδ T cells from NP and RPL patients between peripheral blood and decidua, which will be a useful resource for further studies of the critical roles of γδ T cells in RPL.

Ab Initio Investigation of the Adsorption of CO2 Molecules on Defect Sites of Graphene Surfaces: Role of Local Vacancy Structures.

An in-depth investigation into the adsorption of CO2 on graphene vacancies is essential for the understanding of their applications in various industries. Herein, we report an investigation of the effects of vacancy defects on CO2 gas adsorption behavior on graphene surfaces using the density functional theory. The results show that the formation of vacancies leads to various deformations of local carbon structures, resulting in different adsorption capabilities. Even though most carbon atoms studied can only trigger physisorption, there are also carbon sites that are energetically favored for chemisorption. The general order of the adsorption capabilities of the local carbon atoms is as follows: carbon atoms with dangling bonds > carbon atoms shared by five- and six-membered rings and a vacancy > carbon atoms shared by two six-membered rings and a vacancy. A stronger interaction in the adsorption process generally corresponds to more obvious changes in the partial density of states and a larger amount of transferred charge.

A reactive molecular dynamics study of thermal pyrolysis behavior and mechanisms of lignin during the hydrothermal process: The function of the water molecules.

The lignin hydrothermal processing is an important option but a full understanding of the role played by the water molecules in the depolymerization of lignin is still lacking. In order to clarify the role of the water molecules in the depolymerization of lignin, the evolution of chemical bonds, microstructural changes, and possible mechanisms of product generation were compared during the pyrolysis process under vacuum and water conditions using Reactive Molecular Dynamics Simulation. Compared with vacuum conditions, the role of water changes with temperature, identifying three stages: promotion (1200-1800 K)-inhibition (2100-2400 K)-promotion (2700-3000 K). Also compared with vacuum conditions, hydrothermal processing can promote the cleavage of the ether bonds while inhibiting the destruction of carbocycles. Water molecules promote the depolymerization of lignin into more C4-molecules, thereby generating more combustible gas resources. Based on the research results, the pyrolysis conditions of lignin can be flexibly controlled to obtain solids, liquids or gases.

Phosphohistidine signaling promotes FAK-RB1 interaction and growth factor-independent proliferation of esophageal squamous cell carcinoma.

Current clinical therapies targeting receptor tyrosine kinases including focal adhesion kinase (FAK) have had limited or no effect on esophageal squamous cell carcinoma (ESCC). Unlike esophageal adenocarcinomas, ESCC acquire glucose in excess of their anabolic need. We recently reported that glucose-induced growth factor-independent proliferation requires the phosphorylation of FAKHis58. Here, we confirm His58 phosphorylation in FAK immunoprecipitates of glucose-stimulated, serum-starved ESCC cells using antibodies specific for 3-phosphohistidine and mass spectrometry. We also confirm a role for the histidine kinase, NME1, in glucose-induced FAKpoHis58 and ESCC cell proliferation, correlating with increased levels of NME1 in ESCC tumors versus normal esophageal tissues. Unbiased screening identified glucose-induced retinoblastoma transcriptional corepressor 1 (RB1) binding to FAK, mediated through a "LxCxE" RB1-binding motif in FAK's FERM domain. Importantly, in the absence of growth factors, glucose increased FAK scaffolding of RB1 in the cytoplasm, correlating with increased ESCC G1→S phase transition. Our data strongly suggest that this glucose-mediated mitogenic pathway is novel and represents a unique targetable opportunity in ESCC.

The complete mitochondrial genome of Numenius minutus (Charadriiformes: Scolopacidae): comparative and phylogenetic analysis.

In this study, we used the next-generation sequencing method to obtain mitochondrial DNA (mtDNA) of Numenius minutus Gould 1841 in Scolopacidae, after which we analyzed the structure and phylogeny of the Charadriiformes. The complete mtDNA was 17,047 bp in length, and contained 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA genes, and one control region (CR). The gene structure and arrangement of the mitochondrial genome of 64 Charadriiformes species were basically the same as most birds. The reconstructed phylogenetic tree demonstrated that Numenius species were sister groups and monophyletic in Scolopacidae.

Density Functional Studies on the Atomistic Structure and Properties of Iron Oxides: A Parametric Study.

With the aim to find the best simulation routine to accurately predict the ground-state structures and properties of iron oxides (hematite, magnetite, and wustite) using density functional theory (DFT) with Hubbard-U correction, a significant amount of DFT calculations were conducted to investigate the influence of various simulation parameters (energy cutoff, K-point, U value, magnetization setting, smearing value, etc.) and pseudopotentials on the structures and properties of iron oxides. With optimized simulation parameters, the obtained equation of state, lattice constant, bulk moduli, and band gap is much closer to the experimental values compared with previous studies. Due to the strong coupling between the 2p orbital of O and the 3d orbital of Fe, it was found that Hubbard-U correction obviously improved the results for all three kinds of iron oxides including magnetite which has not yet been tested with U correction before, but the U value should be different for different oxides (3 ev, 4 ev, 4 ev for hematite, magnetite, and wustite, respectively). Two kinds of spin magnetism settings for FeO are considered, which should be chosen according to different calculation purposes. The detailed relationship between the parameter settings and the atomic structures and properties were analyzed, and the general principles for future DFT calculation of iron oxides were provided.

Electroacupuncture relieves hyperalgesia by regulating neuronal-glial interaction and glutamate transporters of spinal dorsal horns in rats with acute incisional neck pain.

Objective: Glial cells are involved in the analgesic effect of electroacupuncture (EA) in rats with chronic neurological pain. The objective of this study was to observe the role of neuronal-glial interaction and glutamate (Glu) transporters in EA-induced acute neck pain relief in rats. Materials and methods: Male rats were placed into the following five groups: control, model, EA Futu (LI18), EA Hegu (LI4)-Neiguan (PC6), and EA Zusanli (ST36)-Yanglingquan (GB34). The incisional neck pain model was established by making a longitudinal incision along the midline of the neck. The thermal pain threshold (TPT) was measured using a radiation heat detector. The immunoactivities of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), neurokinin-1 receptor (NK-1R), Glu aspartate transporter (GLAST), and Glu transporter-1 (GLT-1) in the dorsal horns (DHs) of the cervico-spinal cord (C2-C5) were detected using immunofluorescence histochemistry. The expression levels of GFAP, Iba-1, GLAST, and GLT-1 mRNAs were determined using quantitative real-time polymerase chain reaction (PCR). Results: The TPT and levels of mRNAs expression and immunoactivity of GLT-1 and GLAST were significantly decreased, and those of Iba-1 and GFAP were significantly increased in the model group than those of the control group (P < 0.05). The activated microgliacytes were gathered around the NK-1R positive neurons, and co-expression of NK-1R and astrocytes was observed in the model group. EA LI18 significantly increased the TPT and expression of GLAST and GLT-1 mRNAs (P < 0.05) and notably decreased the number of Iba-1 positive cells and Iba-l mRNA expression (P < 0.05), whereas GLAST and GLT-1 antagonists inhibited the analgesic effect of EA LI18. However, these effects, except for the downregulation of Iba-1 mRNA, were not observed in the EA ST36-GB34 group. Fewer NK-1R-positive neurons were visible in the spinal DHs in the EA LI18 group, and the co-expression of NK-1R and astrocytes was also lower than that in the three EA groups. Conclusion: Electroacupuncture of LI18 had an analgesic effect in rats with neck incisions, which may be related to its functions in suppressing the neuronal-glial cell interaction through NK-1R and upregulating the expression of GLAST and GLT-1 in the spinal DHs.

Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Data on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chinese subjects. METHODS: This is a phase I, open-label, randomized, single-dose, two-way crossover study. Healthy Chinese male subjects were randomized 1:1 to receive a single dose of senaparib 100 mg in two prandial states: fasted or after a high-fat meal; subjects were given a second dose after switching prandial states and a washout period of at least 7 days. Pharmacokinetics were assessed at pre-dose and up to 72 h post-dose. Safety was assessed throughout the study. RESULTS: Sixteen subjects were randomized and included in the pharmacokinetic analysis; 15 completed the study. The presence of food slowed the rate of senaparib absorption (time to maximum concentration) by ~ 3 h and reduced the maximum concentration of senaparib by ~ 24%. Total exposure to senaparib was higher in the fed than fasted state; senaparib area under the plasma concentration-time curve from time zero to the last measurable concentration and area under the plasma concentration-time curve from time zero to infinity were increased by ~ 24 and ~28%, respectively. Safety profiles were similar in both prandial states. All treatment-emergent adverse events were grade 1 in severity; no serious adverse events or deaths were reported. CONCLUSIONS: Food slightly decreased the rate and increased the extent of senaparib absorption following oral administration. However, the effect of food on various exposure parameters was not considered clinically meaningful. Safety data were consistent with the known profile of senaparib and senaparib was well tolerated in the fed and fasted states in healthy subjects. These results indicated that senaparib could be administered orally with or without food. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04057729.