Effects of Dual Inhibition at Dopamine Transporter and σ Receptors in the Discriminative-Stimulus Effects of Cocaine in Male Rats.

Previous studies demonstrated that sigma-receptor (σR) antagonists alone fail to alter cocaine self-administration despite blocking various other effects of cocaine. However, σR antagonists when combined with dopamine transporter (DAT) inhibitors substantially decrease cocaine self-administration. To better understand the effects of this combination, the present study examined the effects of σR antagonist and DAT inhibitor combinations in male rats discriminating cocaine (10 mg/kg, i.p.) from saline injections. The DAT inhibitors alone (WIN 35,428 and methylphenidate) at low (0.1 mg/kg) doses that were minimally active, failed to shift the dose-effect function for discriminative-stimulus effects of cocaine to the left more than two-fold. At 0.32 mg/kg the DAT inhibitors alone shifted the cocaine dose-effect function leftward 24- or 6.6-fold, respectively. The σR antagonists (BD1008, BD1047, and BD1063) failed to fully substitute for cocaine, though BD1008 and BD1047 substituted partially. At 10 mg/kg, BD1008, BD1047, or BD1063 alone shifted the cocaine dose-effect function leftward less than 6.0-fold. In combination with 0.1 mg/kg WIN 35,428, the 10 mg/kg doses of σR antagonists shifted the cocaine dose-effect function from 12.3 to 36.7-fold leftward, and with 0.32 mg/kg WIN 35,428 from 14.3 to 440-fold leftward. In combination with 0.1 mg/kg methylphenidate, those σR antagonist doses shifted the cocaine dose-effect function from 5.5 to 55.0-fold leftward and with 0.32 mg/kg methylphenidate from 10.5 to 48.1-fold leftward. The present results suggest that dual DAT/σR inhibition produces agonist-like subjective effects that may promote decreases in self-administration obtained in previous studies. Significance Statement There is currently no approved medication for treating stimulant abuse, though dopamine-uptake inhibitors in combination with sigma-receptor (σR) antagonists decrease cocaine self-administration in laboratory animals. The present study assessed how this combination alters the discriminative-stimulus effects of cocaine in male rats. Results suggest that concurrent dopamine uptake inhibition and σR antagonism together may promote decreases in self-administration possibly by mimicking the subjective effects extant when subjects cease continued cocaine self-administration.

By Introducing Multiple Hydrogen Bonds Endows MOF Electrodes with an Enhanced Structural Stability.

Recently, metal-organic frameworks (MOFs) have attracted great interest in energy storage areas. However, the poor structural stability of MOFs derived from weak coordination bonds limits their applications. Here, quadruple hydrogen bonds (H-bonds) were introduced onto the MOFs to enhance their structural stability. Cross-linked networks could be formed between molecules owing to multiple H-bonds, strengthening the framework stability. Moreover, the dynamic reversibility of H-bonds could endow MOFs with self-healing ability. Furthermore, due to lower binding energy compared to coordination bonds, H-bonds break preferentially when subjected to internal stress, thus protecting the MOFs. Consequently, the as-prepared self-healing hybrid (SHH-Cu-MOF@Ti3C2TX) exhibited high capacitance retention (89.4%) after 5000 cycles at 1 A g-1, while that hybrid without dynamic H-bonds (H-Cu-MOF@Ti3C2TX) presented a 79.9% retention, delivering an enhancement in cycling stability. Moreover, an asymmetric supercapacitor (ASC) was fabricated by employing SHH-Cu-MOF@Ti3C2TX and activated carbon (AC) as the electrodes. The ASC delivered a specific capacitance (47.4 F g-1 at 1 A g-1), an energy density (16.9 Wh kg-1), and a power density (800 W kg-1) as well as good rate ability (retains 81% of its initial capacitance from 0.2 A g-1 to 5 A g-1).

Combing experimental methods and molecular simulations to study self-healing behaviors of polyurethane elastomers containing multiple hydrogen bond networks and flexible blocks.

The preparation of polymers with high self-healing ability is conducive to environmental protection and resource conservation. In the present work, two kinds of polyurethane (PU) elastomers were prepared: the one containing flexible end blocks (polypropylene glycol) and the other containing flexible end blocks and 2-ureido-4[1H]-pyrimidinone (UPy) groups that can form reversible quadruple hydrogen bonds. Both of the two PU elastomers have self-healing ability. At low temperatures the PU without UPy groups exhibits stronger self-healing ability, while at high temperatures the PU with UPy groups has better self-healing function. The difference can be attributed to the combined effect of segmental mobility and reversible network strength. Based on molecular simulations, we further observed that the self-healing behaviors are affected by four factors: healing temperature, reversible interaction strength, reversible interaction site density and segment diffusion ability.

In Situ Synthesis of Hierarchical Porous Zr-MOFs on Columnar Activated Carbon and Application in Toxic Gas Adsorption.

Metal organic frameworks (MOFs) have been explored as adsorption materials owing to their diversity, controllable structure, high specific surface area, and abundant active sites. However, the shaping of MOFs has become a critical issue hindering their commercial application. A binder or high pressure is commonly used in traditional powder shaping, causing pores to be blocked or collapsed and porosity to be decreased, eventually leading to the degradation of adsorption performance. In this paper, Zr-MOFs were in situ grown on a columnar activated carbon (CAC) matrix, and a series of Zr-MOFs/CAC composites were prepared. The adsorption properties for SO2 and NO2 were measured by dynamic adsorption tests, and the Wheel-Jonas model was used to calculate the saturated adsorption capacity. Abundant mesopores can be formed between MOF crystals and activated carbon particles, and the mesoporosity of Zr-MOFs/CAC composites reached over 50%. Owing to the abundant mesoporous, increased activated sites as well as the synergistic effect between MOFs and activated carbon, the as-obtained HP-Zr-MOFs/CAC exhibited the best adsorption performance both for SO2 and NO2, which are 34.2 and 17.4 mg g-1, respectively, while the adsorption capacities of CAC for SO2 and NO2 are 20.9 and 6.6 mg g-1, respectively. The outstanding performance and facile synthesis process of HP-Zr-MOFs/CAC composites could provide ideas to develop other hierarchical porous MOFs/activated carbon composites.

Studying the effects of carbon nanotube contents on stretch-induced crystallization behavior of polyethylene/carbon nanotube nanocomposites using molecular dynamics simulations.

In the present work, we used molecular dynamics simulations to study the effects of carbon nanotube (CNT) contents on stretch-induced crystallization behavior in CNT filled polyethylene systems. During high-temperature stretching, the stretching is responsible for the orientation of CNTs, which then facilitates segment orientation and conformational transition from the gauche-conformation into the trans-conformation in interfacial regions. The systems with higher CNT contents have a higher degree of orientation and higher contents of trans-conformation during stretching, resulting in the formation of more precursors. During subsequent crystallization, the initial crystallization rate increases with the increase of the CNT content due to the increase in precursor contents in interfacial regions. However, after the CNT content exceeds a certain value, a filler network would be formed by CNTs, which can restrict chain movements and then lead to a decrease in the overall crystallization rate in the systems with high CNT contents.

Constraints on the Velocity and Spin Dependent Exotic Interaction at the Micrometer Range.

We report on an experimental test of the velocity and spin dependent exotic interaction that can be mediated by new light bosons. The interaction is searched by measuring the force between a gold sphere and a microfabricated magnetic structure using a cantilever. The magnetic structure consists of stripes with antiparallel electron spin polarization so that the exotic interaction between the polarized electrons in the magnetic structure and the unpolarized nucleons in the gold sphere varies periodically, which helps to suppress the spurious background signals. The experiment sets the strongest laboratory constraints on the coupling constant between electrons and nucleons at the micrometer range with f_{⊥}<5.3×10^{-8} at λ=5 µm.

Potential regulation of small RNAs on bacterial function activities in pig farm wastewater treatment plants.

Small RNAs (sRNAs) are key players in the regulation of bacterial gene expression. However, the distribution and regulatory functions of sRNA in pig farm wastewater treatment plants (WWTPs) remains unknown. In this study, the wastewaters in anoxic and oxic tanks of the WWTPs were collected. The profiles of the community structure, mRNA expression, and sRNA expression of bacteria in pig farm wastewater were investigated using transcriptome sequencing and qPCR. This study demonstrated that there was a higher abundance of sRNA in the pig farm WWTPs and 52 sRNAs were detected. The sRNAs were mainly present in Proteobacteria and Firmicutes, including the potential human pathogenic bacteria (HPB) (Escherichia, Shigella, Bordetella and Morganella), crop pathogen (Pectobacterium) and denitrifying bacteria (Zobellella). And the sRNAs were involved in the bacterial functional activities such as translation, transcription, drug resistance, membrane transport and amino acid metabolism. In addition, most sRNAs had a higher abundance in anoxic tanks which contained a higher abundance of the genes associated with infectious diseases and drug resistance than that in oxic tanks. The results presented here show that in pig farm WWTPs, sRNA played an important role in bacterial function activities, especially the infectious diseases, drug resistance and denitrification, which can provide a new point of penetration for improving the pig farm WWTPs.

Measurement and analysis of the distortion of factor prices in China.

This study uses the extended C-D production function method to measure the total distortion of factor prices and the distortion of capital, labor and land factor prices in China's provinces and cities. The results indicate that between 2000 and 2019, due to factors such as the dual economic structure between urban and rural areas, human intervention in the capital market, and lagging land marketization reform, both capital and land factor prices showed negative distortions, except for positive distortions in labor factor prices. The degree of this positive distortion began to gradually weaken, and even showed a negative distortion trend in some regions.

Introducing Molecular Sieve into Activated Carbon to Achieve High-Effective Adsorption for Ethylene Oxide.

Presently, ethylene oxide (EtO) is posing a significant threat to both human health and the environment due to occasional or deliberate emissions. However, few works so far have focused on this issue. It is urgent to explore novel and effective technology to protect against the threat of EtO. Herein, a series of AC/ZSM-5 composites were prepared to improve the adsorption performance for EtO, evaluated by dynamic breakthrough experiments. Particularly, the AC/ZSM-20% composite demonstrated a more excellent adsorption capacity of 81.9 mg/g at 25 °C and 50% RH than that of pristine AC and ZSM-5 with 32.5 and 52.3 mg/g, respectively. Moreover, the adsorption capacity of the AC/ZSM-20% composite remained constant even after five adsorption-desorption cycles. The adsorption mechanism of EtO on the composite is further revealed by density functional theory (DFT) calculations.

Custom-printed microfluidic chips using simultaneous ratiometric fluorescence with "Green" carbon dots for detection of multiple antibiotic residues in pork and water samples.

In the evolving field of food safety, rapid and precise detection of antibiotic residues is crucial. This study aimed to tackle this challenge by integrating advanced inkjet printing technology with sophisticated microfluidic paper-based analytical devices (µPADs). The µPAD design utilized "green" quantum dots synthesized via an eco-friendly hydrothermal method using green white mulberry leaves as the carbon source, serving as the key fluorescent detection material. The action mechanism involved a photoinduced electron transfer system using red carbon dots (CDs) as electron donors and blue CDs combined with two-dimensional layered molybdenum disulfide (MoS2) nanosheets as electron acceptors. This system could quickly detect antibiotics within 10 min in pork and water samples, demonstrating high sensitivity and recovery rates: 6.5 pmol/L at 99.75%-110% for sulfadimethoxine, 3.3 pmol/L at 99%-105% for sulfamethoxazole, and 8.5 pmol/L at 98.5%-105% for tetracycline. It achieved a relative standard deviation under 5%, ensuring reliability and reproducibility. The fabricated sensor offered a promising application for the rapid and efficient on-site detection of antibiotic residues in food.

The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.

The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

Metagenomics reveals the characteristics and potential spread of microbiomes and virulence factor genes in the dairy cattle production system.

Virulence factor genes (VFGs) pose a potential threat to ecological security and animal health, and have attracted increasing attention in the livestock industry. As one of the primary livestock types, dairy cattle may be an important source of VFG transmission. However, the distribution, transmission, and evolution of VFGs in the gastrointestinal tract and surrounding environment of dairy cattle remain unclear. In the present study, a total of 263 samples were collected from cows, calves, colostrum, farm wastewater, and soil. Metagenomics was conducted to analyze changes in the microbiome and VFGs characteristics in these ecological niches. The VFGs of the cows showed distinct differences between the rumen and feces, and were influenced by the region. The dominant VFG hosts was regulated by their microbial structure. Colostrum administration of cows increased VFG abundance in their newborn calf feces sharply and Enterobacteriaceae became the primary host. While diet was the primary driving force for the temporal variation in calf VFGs. For samples of the surrounding environment, water and soil had higher VFG concentrations and were more structurally stable. Moreover, extensive interactions between the mobile genetic elements and VFGs and gene mobile analysis map based on metagenomic binning both displayed the potential horizontal transfer ability of VFGs in the cows and environment. Our study revealed the prevalence, diffusion, and regulatory factors of VFGs in dairy cattle production systems, providing novel insights into reducing livestock VFGs and limiting their spread.

Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals.

Postbiotics, which comprise inanimate microorganisms or their constituents, have recently gained significant attention for their potential health benefits. Extensive research on postbiotics has uncovered many beneficial effects on hosts, including antioxidant activity, immunomodulatory effects, gut microbiota modulation, and enhancement of epithelial barrier function. Although these features resemble those of probiotics, the stability and safety of postbiotics make them an appealing alternative. In this review, we provide a comprehensive summary of the latest research on postbiotics, emphasizing their positive impacts on both human and animal health. As our understanding of the influence of postbiotics on living organisms continues to grow, their application in clinical and nutritional settings, as well as animal husbandry, is expected to expand. Moreover, by substituting postbiotics for antibiotics, we can promote health and productivity while minimizing adverse effects. This alternative approach holds immense potential for improving health outcomes and revolutionizing the food and animal products industries.

Development of sensory integration therapy in Mainland China: A comprehensive study with bibliometrics and visualization techniques.

Sensory integration therapy (SIT) is an intervention to improve the developmental and learning problems in children. It was introduced in China from late 1980 s to early 1990 s and has received considerable attention from scholars. However, due to its late development in China and its specialised nature, it is worth exploring in depth whether it is recognized by the general public and how it is researched by academics. Therefore, we used Internet survey approach to explore the actual feedback of users towards SIT through the Internet. At the same time, bibliometric method and visualization techniques were used to study 892 journal articles on SIT in CNKI, Wanfang Database and VIP Database to analyze the spatial and temporal distribution, subject distribution, keyword co-occurrence, and keyword clustering of SIT research in mainland China since it came to China mainland. We found that the research on SIT in mainland China has been fruitful. However, the public is less aware of its basic function, therapeutic effects, and necessity. Our findings point to the need to raise awareness of sensory integration disorder and sensory integration therapy among the general public, and to strengthen academic research on sensory integration therapy.

The Effect of Topology on Block Copolymer Nanoparticles: Linear versus Star Block Copolymers in Toluene.

Linear and star block copolymer (BCP) nanoparticles of (polystyrene-block-poly(4-vinylpyridine))n (PS-b-P4VP)n with arm numbers of 1, 2, 3, and 4 were prepared by two methods of polymerization-induced self-assembly (PISA) and general self-assembly of block copolymers in the low-polar organic solvent, toluene. The effect of the arm number on the size and/or morphology of the (PS-b-P4VP)n nanoassemblies synthesized by the two methods in toluene and on the polymerization kinetics was investigated in detail. Our results show that in toluene, a low-polar solvent, the topology not only affected the morphology of the BCP nanoparticles prepared by PISA, but also influenced the BCP nanoparticles synthesized through general self-assembly.

Triboelectric Plasma CO2 Reduction Reaching a Mechanical Energy Conversion Efficiency of 2.3.

Mechanical energy-induced CO2 reduction is a promising strategy for reducing greenhouse gas emissions and simultaneously harvesting mechanical energy. Unfortunately, the low energy conversion efficiency is still an open challenge. Here, multiple-pulse, flow-type triboelectric plasma with dual functions of harvesting mechanical energy and driving chemical reactions is introduced to efficiently reduce CO2 . CO selectivity of 92.4% is achieved under normal temperature and pressure, and the CO and O2 evolution rates reach 12.4 and 6.7 µmol h-1 , respectively. The maximum energy conversion efficiencies of 2.3% from mechanical to chemical energy and 31.9% from electrical to chemical energy are reached. The low average electron energy in triboelectric plasma and vibrational excitation dissociation of CO2 with low barrier is revealed by optical emission spectra and plasma simulations, which enable the high energy conversion efficiency. The approach of triboelectric plasma reduction reported here provides a promising strategy for efficient utilization of renewable and dispersed mechanical energy.

N-substituted benztropine analogs: selective dopamine transporter ligands with a fast onset of action and minimal cocaine-like behavioral effects.

Previous studies suggested that differences between the behavioral effects of cocaine and analogs of benztropine were related to the relatively slow onset of action of the latter compounds. Several N-substituted benztropine analogs with a relatively fast onset of effects were studied to assess whether a fast onset of effects would render the effects more similar to those of cocaine. Only one of the compounds increased locomotor activity, and the increases were modest compared with those of 10 to 20 mg/kg cocaine. In rats trained to discriminate 10 mg/kg cocaine from saline none of the compounds produced more than 40% cocaine-like responds up to 2 h after injection. None of the compounds produced place-conditioning when examined up to 90 min after injection, indicating minimal abuse liability. The compounds had 5.6 to 30 nM affinities at the dopamine transporter (DAT), with uniformly lower affinities at norepinephrine and serotonin transporters (from 490-4600 and 1420-7350 nM, respectively). Affinities at muscarinic M(1) receptors were from 100- to 300-fold lower than DAT affinities, suggesting minimal contribution of those sites to the behavioral effects of the compounds. Affinities at histaminic H(1) sites were from 11- to 43-fold lower than those for the DAT. The compounds also had affinity for sigma, 5-hydroxytryptamine(1) (5-HT(1)), and 5-HT(2) receptors that may have contributed to their behavioral effects. Together, the results indicate that a slow onset of action is not a necessary condition for reduced cocaine-like effects of atypical DAT ligands and suggest several mechanisms that may contribute to the reduced cocaine-like efficacy of these compounds.

Analysis of Influencing Factors of PM2.5 Concentration and Design of a Pollutant Diffusion Model Based on an Artificial Neural Network in the Environment of the Internet of Vehicles.

With the development of the automobile industry, artificial intelligence, big data, 5G, and other technologies, the Internet of Vehicles (IoV) industry has entered a stage of rapid development. In this paper, a pollutant diffusion model based on an artificial neural network is designed in the context of a vehicle network. The application of artificial neural networks in haze prediction is studied. This paper first analyzes the causes and influencing factors of haze and selects the most representative and relatively large meteorological factors from temperature, wind, relative humidity, and several pollutant factors. Through training and simulation, a haze prediction model in the Beijing, Tianjin, and Hebei regions of China is established. Finally, according to the collected meteorological data, the pollutant diffusion model is established. The model is deduced by a standard mathematical formula, which makes the prediction results more accurate and rigorous, and the main conclusions and feasible scientific suggestions are obtained. The simulation results show that the method is effective. By strengthening the service system of the IoV, meteorological services can be more intelligent, and the information acquisition and service ability of the vehicle network can be effectively improved.

The Regulation of O2 Spin State and Direct Oxidation of CO at Room Temperature Using Triboelectric Plasma by Harvesting Mechanical Energy.

Oxidation reactions play a critical role in processes involving energy utilization, chemical conversion, and pollutant elimination. However, due to its spin-forbidden nature, the reaction of molecular dioxygen (O2) with a substrate is difficult under mild conditions. Herein, we describe a system that activates O2 via the direct modulation of its spin state by mechanical energy-induced triboelectric corona plasma, enabling the CO oxidation reaction under normal temperature and pressure. Under optimized reaction conditions, the activity was 7.2 µmol h-1, and the energy consumption per mole CO was 4.2 MJ. The results of kinetic isotope effect, colorimetry, and density functional theory calculation studies demonstrated that electrons generated in the triboelectric plasma were directly injected into the antibonding orbital of O2 to form highly reactive negative ions O2-, which effectively promoted the rate-limiting step of O2 dissociation. The barrier of the reaction of O2- ions and CO molecular was 3.4 eV lower than that of O2 and CO molecular. This work provides an effective strategy for using renewable and green mechanical energy to realize spin-forbidden reactions of small molecules.

Herpes simplex virus type 1 latency-associated transcript inhibits apoptosis and promotes neurite sprouting in neuroblastoma cells following serum starvation by maintaining protein kinase B (AKT) levels.

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is expressed abundantly in latently infected sensory neurons. LAT-deletion-mutant virus strains have reduced-reactivation phenotypes in small animal models of infection, demonstrating that LAT plays an important role in the latency-reactivation cycle of HSV-1. Previous studies demonstrated that the anti-apoptosis functions of LAT are important for regulating the latency-reactivation cycle because three different anti-apoptosis genes can substitute for LAT. Although LAT inhibits caspase 3 activation, the signalling pathway by which LAT inhibits caspase 3 activation was not identified. In this study, we analysed mouse neuroblastoma cells (C1300) that express LAT stably (DC-LAT6 cells) following serum starvation. As expected, DC-LAT6 cells were resistant to apoptosis following serum withdrawal. Levels of total and phosphorylated AKT (protein kinase B), a serine/threonine protein kinase that promotes cell survival, were higher in DC-LAT6 cells after serum withdrawal than in C1300 cells or a cell line stably transfected with a LAT promoter mutant (DC-DeltaLAT311). A specific AKT inhibitor reduced the anti-apoptosis functions of LAT and phosphorylated AKT levels. After serum withdrawal, more DC-LAT6 cells sprouted neurites and exhibited a differentiated morphology. NeuN (neuronal nuclei), a neuron-specific nuclear protein, was expressed abundantly in DC-LAT6 cells, but not C1300 cells, after serum withdrawal, further supporting the concept that LAT enhanced neuronal-like morphology. Collectively, these studies suggested that LAT, directly or indirectly, maintained total and phosphorylated AKT levels, which correlated with increased cell survival and mature neuronal-like morphology.