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Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

Drug addiction is a debilitating condition that causes severe mental and physical impairments. Methamphetamine (METH) is one of the most commonly abused psychostimulants, mainly affecting the brain by releasing dopamine and serotonin. METH addiction has become a serious public health issue, and there is currently no specific treatment available. Although scientists have a good understanding of the mechanisms underlying drug addiction, including METH, our current biological and molecular knowledge of addiction is still incomplete. There is substantial evidence that addiction‐related changes are primarily mediated through gene expression regulation. Interestingly, the involvement of microRNAs (miRNAs) in this process could enhance our understanding of the molecular mechanisms underlying METH addiction. Therefore, further understanding the mechanisms behind METH‐induced differential changes in miRNAs, along with their pharmacological and genetic manipulation, could lead to promising new treatments for METH addiction. In this study, we first summarized epidemiological data and the addictive and neurotoxic mechanisms of METH, extensively reviewed studies on miRNA expression changes, discussed potential miRNA‐targeted therapeutic interventions for METH addiction, and outlined future research directions. We believe this study will provide a clearer understanding of the role of miRNAs in METH addiction and may help scientists develop more effective therapeutic strategies. The use of METH leads to the release of dopamine from the affected brain regions, including the nucleus accumbens (NAc), ventral tegmental area (VTA), prefrontal cortex (PFC), hippocampus (Hip), and striatum. This triggers signals that alter miRNA expression, which in turn leads to differential expression of target genes. Alterations in target gene expression activate addiction‐related signaling pathways, including CREB, MAPK/PI3K/Akt, LTP, GPCR, GnRH, and other pathways. This finally results in METH addiction, and with persistent drug intake, leads to METH‐mediated neurotoxicity, seen as dopaminergic neuron degeneration and cognitive and behavioral deficits.

Nanoscaled aluminum nitride （AlN） dispersion strengthened 2024 aluminum alloy was fabricated using a novel approach in which Al-Mg-Cu compacts were partially nitrided in flowing nitrogen gas. The compacts were subsequently consolidated by sintering and hot extrusion. The microstructure and mechanical properties of the material were preliminarily investigated. Transmission electron microscopy and X-ray diffraction results revealed that AlN particles were generated by the nitridation of Al-Mg-Cu compacts. The material exhibited excellent mechanical properties after hot extrusion and heat treatment. The ultimate tensile and yield strengths of the extruded samples containing 8.92vol% AlN with the T6 heat treatment were 675 and 573 MPa, respectively.

Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

This paper proposes a concept of soil shear strength exertion around an anchorage section to analyze and calculate the anchor’s force and displacement. First, based on the Mohr stress circle, the numerical relationship between the value of the internal friction angle exertion, the value of the cohesion exertion, and the displacement are established under the non-limit active state. According to the interaction mechanism between the anchorage section and the surrounding soil, this paper obtains the corresponding relationship between the value of the soil’s shear strength exertion and displacement under the non-limit active state. Then, according to the load transfer principle of the anchorage section, the basic differential equation is established. The differential equation of the relative displacement distribution along the length of the anchorage section under the non-limit active state is further derived. And the calculation and analysis formula of the shear stress and relative displacement in the anchorage section considering the process of the soil shear strength exertion is also obtained. Finally, this paper compares the calculation method with the hyperbolic model calculation method for the same example. The results verify the accuracy of the calculation method.

Transboundary river water resources allocation is important in water resources management. Conflicts often arise when different water users compete for a limited water supply. This study proposes a two-level asymmetric Nash–Harsanyi Leader–Follower game model to resolve conflicts of interest in transboundary river water resources allocation problems. In the proposed model, we use bankruptcy theory to derive disagreement points and determine the bargaining weights considering the principles of equity and efficiency. For comparison, a model that does not consider disagreement points and bargaining weights are also used to demonstrate the importance of disagreement points and bargaining weights. The proposed model is applied to a real case of the Huaihe River basin in China, which is facing water shortages. In the case study, the watershed management agency serves as the leader, three provinces (Henan, Anhui and Jiangsu) serve as followers, and successive linear programming is used to solve the model for followers. The results show that the proposed disagreement points can guarantee basic water demand, and the bargaining weights can better balance the economic development levels among followers.

Flood control operation in a multi-reservoir system is a multi-criteria decision-making (MCDM) problem, in which the considered criteria are often correlated with each other. In this paper, we propose an MCDM model for reservoir flood control operation to deal with correlation among criteria. Considering the flood control safety of reservoirs and downstream protected regions, we establish the hierarchical structure of the criterion system. We use the principal component analysis method to eliminate the correlation, and transform the original criterion system into an independent comprehensive criterion system. The comprehensive decision matrix coupled with the weight vector obtained by the improved entropy weight method serves as the input to TOPSIS method, fuzzy optimum method, and fuzzy matter-element method, by which we determine the ranking order of the alternatives. We apply the proposed model to a cascade system of reservoirs at the Daduhe River basin in China. The results show that the dimensionality of the criterion system is reduced and the correlation among criteria is eliminated simultaneously, and the ranking order of the alternatives is reasonable. The proposed model provides an effective way to deal with correlation among criteria, and can be extended to wider applications in many other MCDM problems.

Mitigating the function of acquired transgenes in crop wild/weedy relatives can provide an ideal strategy to reduce the possible undesired environmental impacts of pollen-mediated transgene flow from genetically engineered (GE) crops. To explore a transgene mitigation system in rice, we edited the seed-shattering genes, SH4 and qSH1, using a weedy rice line (“C9”) that originally had strong seed shattering. We also analyzed seed size-related traits, the total genomic transcriptomic data, and RT-qPCR expression of the SH4 or qSH1 gene-edited and SH4/qSH1 gene-edited weedy rice lines. Substantially reduced seed shattering was observed in all gene-edited weedy rice lines. The single gene-edited weedy rice lines, either the SH4 or qSH1 gene, did not show a consistent reduction in their seed size-related traits. In addition, reduced seed shattering was closely linked with the weakness and absence of abscission layers and reduced abscisic acid (ABA). Additionally, the genes closely associated with ABA biosynthesis and signaling transduction, as well as cell-wall hydrolysis, were downregulated in all gene-edited weedy rice lines. These findings facilitate our deep insights into the underlying mechanisms of reduced seed shattering in plants in the rice genus Oryza. In addition, such a mitigating technology also has practical applications for reducing the potential adverse environmental impacts caused by transgene flow and for managing the infestation of weedy rice by acquiring the mitigator from GE rice cultivars through natural gene flow.

IntroductionMechanical neck pain (MNP) is defined as pain in the area of the neck and/or neck-shoulder provoked by body mechanics and which adversely affects physical, psychological and social function. The treatments for MNP are limited. Previous studies and clinical experience have indicated that myofascial acupuncture might be a better treatment option for MNP, but the efficacy is controversial. Therefore, our aim is to compare the efficacy of myofascial acupuncture and routine acupuncture for MNP.Methods and analysisThe study is a multicentre, prospective randomised clinical trial. Patients will be recruited from four tertiary hospitals in China. A total of 438 participants with MNP will be randomly assigned into two groups, namely the ‘Sancai-Tianbu’ myofascial acupuncture group and the routine acupuncture group, at a ratio of 1:1. Each group will receive the acupuncture treatment twice a week for 21 days, totalling six sessions. The primary outcome will be the Visual Analogue Scale score. The secondary outcomes will be the Neck Disability Index, the cervical range of motion and the MOS 36-Item Short Form Health Survey. The assessments will be performed at baseline (immediately after allocation), pretreatment (5 min before every treatment), post-treatment (within 10 min after every treatment), postcourse (within 1 day after the course), and at 1, 3 and 6 months after the course. All patients will be included in the intent-to-treat analysis. Repeated-measure analysis of covariance will be used to determine the effects of the intervention on the outcome measures.Ethics and disseminationEthics approval was obtained from China Aerospace Science & Industry Corporation 731 Hospital, with permission number 2022-0204-01. Written informed consent will be obtained from the enrolled patients. Trial results will be disseminated in peer-reviewed publications.Trial registration numberChiCTR2200061453.

Purpose Investigation of the role of sedation during colonoscopy is meaningful as the advantages of colonoscopy performing with sedation are still controversial. Methods Medical records of patients who underwent colonoscopy in our institution were retrospectively analyzed. The sedation rate, adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation rate (CIR), iatrogenic colonic perforation rate (ICP) were calculated. Results A total of 48,838 colonoscopies (24,498 in males) dated from July 2007 to February 2017 were analyzed. The median age was 50 years (range 16–85 years). An overall sedation rate was 80.38%. The PDR was 26.77%, and was not statistically different between colonoscopy with or without sedation (26.67% vs 27.22, p  = 0.474). ADR was 12.9% regardless of applying sedation or not (13.0% vs 12.44%, p  = 0.337). The CIR was 87.42% in all examinations with an adjusted CIR of 90.34%, and was higher when performed with sedation than without sedation (88.92% vs 80.64%, p  < 0.0001). Five cases (0.01%) of ICP were reported, all of which occurred in patients under sedation. Conclusions The use of sedation is associated with increased CIR, but ADR and PDR remain unchanged with or without sedation. However, perforation rate, albeit very low, is significantly higher in sedated patients.