Promises and challenges of cardiac organoids.

Cardiovascular diseases are currently the main cause of death. The study of the pathogenesis and treatment of these diseases is still a major challenge. Traditional 2D cultured cells and animal models have certain limitations. Heart organoids as models can simulate the structure and function of the body, providing a new research strategy. This paper mainly discusses the development of organoids and their application in the study of the cardiac developmental process, drug screening and treatment of genetic and non-genetic diseases, concluding with their strengths and weaknesses.

Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats.

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.

Genetic Polymorphism of 24 Autosomal STR in the Population of Rwanda.

Rwanda is one of the smallest countries of Africa, where forensic genetic studies are rarely being conducted and very few DNA databases have been developed. Short tandem repeats (STRs) polymorphisms were investigated in 505 unrelated Rwandese by using the HUMDNA TYPING (Yanhuang) Kit. The following STRs were targeted: D3S1358, D13S317, D7S820, D16S539, SE33, D10S1248, D5S818, D21S11, TPOX, D1S1656, D6S1043, D19S433, D22S1045, D8S1179, Penta E, D2S441, D12S391, D2S1338, vWA, Penta D, TH01, D18S51, CSF1PO and FGA. The purpose of this study was to elucidate the genetic diversity and explore the potential of applying these 24 STR in 505 Rwandan population in forensics. A total of 360 alleles, with corresponding allele frequencies in the range from 0.001 to 0.442, were found in the Rwandan population. SE33 presented the highest polymorphism (PIC=0.921) among these 24 loci, whereas D13S317 presented the lowest one (PIC=0.671). No deviation from the Hardy-Weinberg equilibrium was observed for any of the 24 loci. The forensic parameters, including the combined power of discrimination (PD and the combined exclusion power, have demonstrated that this panel of 24 STRs is highly informative and useful for forensic applications such as individuals' identification and paternity tests. Additionally, the genetic distances between Rwanda population and other 24 published populations were calculated based on 8 overlapping loci with the polygenetic tree revealing significant clusters in the populations associated with their geographic locations and their historical relationship.

Influence of in-Vehicle Audio Warning on Drivers' Eye-Movement and Behavior at Flashing Light-Controlled Grade Crossings.

OBJECTIVE: This study aims to evaluate the effect of in-vehicle audio warning at flashing-light-controlled grade crossings based on driving simulation and eye-tracking systems. BACKGROUND: Collisions at flashing-light-controlled grade crossings have severe consequences. In-vehicle audio warning has the potential to regulate driver behavior. However, whether this improvement occurs through priming drivers' visual search patterns is not yet clear. METHOD: Drivers' visual activity and behaviors were recorded. The effect of a warning was tested with a series of flashing light trigger times (FLTTs) ranging from 2s to 6s with a 1s increment. Different driving conditions (i.e., clear and fog) and driver experience were considered in the experiment design. RESULTS: Warnings could guide the allocation of both overt and covert attention, as well as raise drivers' situation awareness, manifesting as the enhanced perception of signs and better understanding of the flashing red light. Significant improvement in the stop-compliance rate was found in warning scenarios, particularly with a late FLTT. The decreased saccade duration and increased fixation duration on the signal implied a dilemma-zone effect when the FLTT was lower than 4s. Furthermore, reduced fixation duration on signs and signals was found in foggy conditions. Non-professional drivers had a wider search range than their counterparts. CONCLUSION: In-vehicle audio warning is an effective countermeasure for improving crossing safety by optimizing visual search strategy. APPLICATION: In-vehicle audio warnings warrant promotion at grade crossings based on the driver assistance system.

The updated view on induced pluripotent stem cells for cardiovascular precision medicine.

Cardiovascular diseases have consistently been one of the leading causes of mortality, despite investigations by many scientists and clinicians. Animal models are versatile platforms to illustrate various mechanisms of different diseases, but are lacking in accurately portraying cardiovascular disease phenotypes. The advent of human pluripotent stem cells (PSCs) has led to much development in the construction of cardiovascular disease models. In this review, we provide a brief overview of the history and utilization of PSCs for cardiovascular precision medicine, including disease modeling, drug screening, and gene editing, and elaborate on the current updated research status of patient-specific induced pluripotent stem cell (iPSC)-based disease models for cardiac channelopathies, cardiomyopathies, and other cardiovascular diseases. Furthermore, we highlight the development of novel human iPSC-derived engineered heart tissues for cardiovascular disease modeling. Finally, we put forward our own views on the existing advantages and difficulties for moving forward in this field.

Age estimation using pulp/enamel volume ratio of impacted mandibular third molars measured on CBCT images in a northern Chinese population.

The present study aims to evaluate the relation between chronological age and the ratio of pulp volume (PV) to enamel volume (EV) of impacted mandibular third molars (IMTMs) by using cone-beam computed tomography (CBCT) images and an improved 3D image segmentation technique. A sample of CBCT images of IMTM was collected from 414 northern Chinese subjects (214 male and 200 female clinical patients) ranging in age from 20 to 65 years. The GrowCut effect image segmentation (GCEIS) module algorithm was used to calculate the PV and EV from CBCT images. The total sample was divided into a training group and validation group in a ratio of 7 to 3. The PV/EV ratio (PEr) in the training sample was used to develop a mathematical formula for age estimation as follows: age = - 5.817-21.726 × Ln PEr (p < 0.0001) (Ln, natural logarithm). The mean absolute error (MAE) and root mean square error (RMSE) were used to determine the precision and accuracy of the mathematical formula in the validation group and all samples. The MAEs in the male, female, and pooled gender samples were 9.223, 7.722, and 8.41, respectively, and the RMSEs in the male, female, and pooled gender samples were 10.76, 9.58, and 9.986, respectively. The precise and accurate results indicate that the PEr of IMTM in CBCT images is a potential index for dental age estimation and is possible to be used in forensic medicine.

Novel Association between Flavin-Containing Monooxygenase 3 Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population.

Some effective antithyroid drugs (ATDs) have been widely used for patients with Graves' disease (GD) but are associated with ATD-induced agranulocytosis. We selected 29 ATD-induced agranulocytosis patients, 44 ATD-induced neutropenia patients, and 140 GD controls among the Chinese Han population who were recruited at the First Affiliated Hospital of Xi'an Jiao Tong University. We assessed their response to ATDs treatment by performing genotyping for a candidate gene association study of samples from patients receiving treatment. Human flavin-containing monooxygenase 3 (FMO3), which is the major hepatic enzyme involved in the production of N-oxide of trimethylamine, catalyzes the oxygenation of a variety of drug compounds. Six single SNP, genotype, haplotype (HAP), and association analyses of the FMO3 gene with ATD-induced agranulocytosis/neutropenia under different models (i.e., additive, dominant, and recessive models) were performed. Rs1736557, which caused an amino acid variation V257M, showed a strong association between ATD-induced agranulocytosis and GD controls after Bonferroni correction (p = 0.011, OR 2.301, 95% CI 1.201-4.409). The presence of HAP 3 (HAP3) in the FMO3 gene HAP was statistically associated with ATD-induced agranulocytosis (p = 0.038, permutation p value). Our findings indicate that genetic variations in the FMO3 gene are associated with the response to ATDs maintenance treatment in ATD-induced agranulocytosis patients of -Chinese Han population.

Structural and biochemical characterization of the yeast HD domain containing protein YGK1 reveals a metal-dependent nucleoside 5'-monophosphatase.

HD-domain is a conserved domain, with the signature of histidine and aspartic (HD) residues doublets. HD-domain proteins may possess nucleotidase and phosphodiesterase activities, and they play important roles in signaling and nucleotide metabolism. In yeast, HD-domain proteins with nucleotidase activity remained unexplored. Here, we biochemically and structurally characterized two HD domain proteins YGK1 (YGL101W) and YB92 (YBR242W) from Saccharomyces cerevisiae as nucleoside 5'-monophosphatases, with substrate preference for deoxyribonucleoside 5'-monophosphatase over ribonucleoside 5'-monophosphatase. By determining the crystal structure of YGK1, we unveiled that YGK1 structure resembled as the crystal structure of YfbR from E. coli. Size-exclusion chromatography and crosslinking studies suggested that YGK1 and YB92 existed in the form of a dimer, respectively, which were consistent with structural observation of YGK1. Site-directed mutagenesis demonstrated that more extensive conserved residues near the divalent metal coordinating active site were essential for YGK1 activity than previous suggested. The metal coordinating His89 and Asp90, and the neighboring conserved Glu93, Glu114 and Glu145 were individually critical for catalysis. In addition, alignments suggested that three flexible loops with hydrophobic residues might be implicated in substrate selectivity to nucleoside moiety. Together, our comparative structural and mutational studies suggested that YGK1 and YB92 functioned as 5'-nucleotidases in S. cerevisiae.

A Trichromatic and White-Light-Emitting MOF Composite for Multi-Dimensional and Multi-Response Ratiometric Luminescent Sensing.

Present here is a new dual ratiometric luminescent probe D which is a trichromatic and white-light-emitting metal-organic framework (MOF) composite facilely obtained by incorporating red/green-emitting complex modules into a blue-emitting MOF. Probe D exhibits remarkable capabilities of sensing different volatile organic solvents (VOSs) via 2D code recognition of the two VOS-dependent MOF ligand-to-module ratios of the emission-peak intensities. For specific VOSs, the resultant luminescent color changes from the starting white color are sharp enough to be visible to the naked eye. Remarkably, D can differentiate solution-phase nitroaromatics and metal ions by recording the evolution of the two ratios during titration processes, enabling an unusual 3D code recognition using the titrant amount as the third dimension for the first time. D also can be used to detect dinoseb, Fe3+ and Al3+ ions quantitatively by analysis of the ratios with detection limits as low as 0.050, 0.41, and 0.12 ppm, respectively. Clearly, such a self-referencing trichromatic probe can maximize the output information and significantly enhance the detection selectivity and sensitivity via multi-dimensional sensing, and has great potentials for practical applications.

Phase 3 Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

BACKGROUND: The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries. METHODS: In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol. RESULTS: Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups. CONCLUSIONS: The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV.

Structural insight into the E. coli HigBA complex.

The toxin-antitoxin system is ubiquitously existed in bacteria and archaea, performing a wide variety of functions modulating cell fitness in response to environmental cues. In this report, we solved the crystal structure of the toxin-antitoxin HigBA complex from E. coli K-12 to 2.7 Å resolution. The crystal structure of the HigBA complex displays a hetero-tetramer (HigBA)2 form comprised by two HigB and two HigA subunits. Each toxin HigB resumes a microbial RNase T1 fold, characteristic of a three antiparallel ß-sheet core shielded by a few α-helices at either side. Each antitoxin HigA composed of all α-helices resembles a "C"-shaped clamp nicely encompassing a HigB in the (HigBA)2 complex. Two HigA monomers dimerize at their N-terminal domain. We showed that HigA helix α1 was essential for HigA dimerization and the hetero-tetramer (HigBA)2 formation, but not for a hetero-dimeric HigBA formation. HigA dimerization mediated by helix α1 was dispensable for DNA-binding, as a heterodimeric HigBA complex still bound to the higBA operator in vitro. The HigA C-terminal domain with a helix-turn-helix fold was essential for DNA binding. We also defined two palindromes in higBA operator specifically recognized by HigA and HigBA in vitro.

BubR1 controls starvation-induced lipolysis via IMD signaling pathway in Drosophila.

Lipolysis, the key process releasing fat acids to generate energy in adipose tissues, correlates with starvation resistance. Nevertheless, its detail mechanisms remain elusive. BubR1, an essential mitotic regulator, ensures proper chromosome alignment and segregation during mitosis, but its physiological functions are largely unknown. Here, we use Drosophila adult fat body, the major lipid storage organ, to study the functions of BubR1 in lipolysis. We show that both whole body- and fat body-specific BubR1 depletions increase lipid degradation and shorten the lifespan under fasting but not feeding. Relish, the conserved regulator of IMD signaling pathway, acts as the downstream target of BubR1 to control the expression level of Bmm and modulate the lipolysis upon fasting. Thus, our study reveals new functions of BubR1 in starvation-induced lipolysis and provides new insights into the molecular mechanisms of lipolysis mediated by IMD signaling pathway.

Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs.

Generation of human vascularized and chambered cardiac organoids for cardiac disease modelling and drug evaluation.

Human induced pluripotent stem cell (hiPSC)-derived cardiac organoids (COs) have shown great potential in modelling human heart development and cardiovascular diseases, a leading cause of global death. However, several limitations such as low reproducibility, limited vascularization and difficulty in formation of cardiac chamber were yet to be overcome. We established a new method for robust generation of COs, via combination of methodologies of hiPSC-derived vascular spheres and directly differentiated cardiomyocytes from hiPSCs, and investigated the potential application of human COs in cardiac injury modelling and drug evaluation. The human COs we built displayed a vascularized and chamber-like structure, and hence were named vaschamcardioids (vcCOs). These vcCOs exhibited approximately 90% spontaneous beating ratio. Single-cell transcriptomics identified a total of six cell types in the vcCOs, including cardiomyocytes, cardiac precursor cells, endothelial cells, fibroblasts, etc. We successfully recaptured the processes of cardiac injury and fibrosis in vivo on vcCOs, and showed that the FDA-approved medication captopril significantly attenuated cardiac injury-induced fibrosis and functional disorders. In addition, the human vcCOs exhibited an obvious drug toxicity reaction to doxorubicin in a dose-dependent manner. We developed a three-step method for robust generation of chamber-like and vascularized complex vcCOs, and our data suggested that vcCOs might become a useful model for understanding pathophysiological mechanisms of cardiovascular diseases, developing intervention strategies and screening drugs.

Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

A randomized, double-blind, placebo-controlled phase I clinical trial of rotavirus inactivated vaccine (Vero cell) in a healthy adult population aged 18-49 years to assess safety and preliminary observation of immunogenicity.

We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).

Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Porphyromonas gingivalis induces an inflammatory response via the cGAS-STING signaling pathway in a periodontitis mouse model.

Periodontitis is an inflammatory disease initiated by periodontopathogenic bacteria in the dental plaque biofilms. Understanding the role of Porphyromonas gingivalis (P. gingivalis), a keystone pathogen associated with chronic periodontitis, in the inflammatory response is crucial. Herein, we investigated whether P. gingivalis infection triggers the expression of the type I IFN gene and various cytokines and leads to activation of the cGAMP synthase-stimulator of IFN genes (cGAS-STING) pathway both in vitro and in a mouse model. Additionally, in an experimental model of periodontitis using P. gingivalis, StingGt mice showed lower levels of inflammatory cytokines and bone resorption than wild-type mice. Furthermore, we report that a STING inhibitor (SN-011) significantly decreased inflammatory cytokine production and osteoclast formation in a periodontitis mouse model with P. gingivalis. In addition, STING agonist (SR-717) -treated periodontitis mice displayed enhanced macrophage infiltration and M1 macrophage polarization in periodontal lesions compared with that in vehicle-treated periodontitis mice. In conclusion, our results demonstrate that the cGAS-STING signaling pathway may be one of the key mechanisms crucial for the P. gingivalis-induced inflammatory response that leads to chronic periodontitis.

The 5-HT7 receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats.

The 5-hydroxytryptamine 7 receptor (5-HT7R) is one of the most recently cloned serotonin receptors which have been implicated in many physiological and pathological processes including drug addiction. Behavioral sensitization is the progressive process during which re-exposure to drugs intensified the behavioral and neurochemical responses to drugs. Our previous study has demonstrated that the ventrolateral orbital cortex (VLO) is critical for morphine-induced reinforcing effect. The aim of the present study was to investigate the effect of 5-HT7Rs in the VLO on morphine-induced behavioral sensitization and their underlying molecular mechanisms. Our results showed that a single injection of morphine, followed by a low challenge dose could induce behavioral sensitization. Microinjection of the selective 5-HT7R agonist AS-19 into the VLO during the development phase significantly increased morphine-induced hyperactivity. Microinjection of the 5-HT7R antagonist SB-269970 suppressed acute morphine-induced hyperactivity and the induction of behavioral sensitization, but had no effect on the expression of behavioral sensitization. In addition, the phosphorylation of AKT (Ser 473) was increased during the expression phase of morphine-induced behavioral sensitization. Suppression of the induction phase could also block the increase of p-AKT (Ser 473). In conclusion, we demonstrated that 5-HT7Rs and p-AKT in the VLO at least partially contribute to morphine-induced behavioral sensitization.

Triboelectrostatic charging behavior of pulse particles in a vortex flow tribocharger.

Triboelectrostatic separation (TES) has shown its great potential in dry fractionation of food ingredients. The principle of the TES technique is straightforward, i.e., charging particles through interactions of particle-particle and/or particle-wall of the contact material, followed by the effect of an electric field. However, optimization of TES efficiency is complex due to obscure understandings, unknowns, and inconsistencies in the charging mechanism between the tribocharger and the agro-food materials. To broaden the design and applications of the TES technique and shed some light on the charging mechanism, experiments were conducted in a vortex flow tribocharger made of three different materials (Copper, Stainless Steel, and PTFE) to investigate the chargeability of five type of selected pulses particles. A Faraday cup measurement system was applied to measure the electric charge of the particles collected at the core and wall regions of the tribocharger. The charges of the pulse particles induced by the vibratory feeder were also measured to verify the chargeability of the particles. Ideal charging material was suggested by comparing the specific charge of particles using the three vessels. A simple "wave propagation" mode based on the vortex flow dynamics has been proposed with an attempt to explore the role of particle-particle and particle-wall interactions on the triboelectrostatic charging.