Low-coordinated Mn-N2 sites in graphene oxide induce peroxydisulfate activation for tetracycline degradation: Process optimization and theoretical calculation.

Atom-dispersed low-coordinated transition metal-Nx catalysts exhibit excellent efficiency in activating peroxydisulfate (PDS) for environmental remediation. However, their catalytic performance is limited due to metal-N coordination number and single-atom loading amount. In this study, low-coordinated nitrogen-doped graphene oxide (GO) confined single-atom Mn catalyst (Mn-SA/NGO) was synthesized by molten salt-assisted pyrolysis and coupled to PDS for degradation of tetracycline (TC) in water. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) analysis showed the successful doping of single-atom Mn (weight percentage 1.6%) onto GO and the formation of low-coordinated Mn-N2 sites. The optimized parameters obtained by Box-Behnken Design achieved 100% TC removal in both prediction and experimental results. The Mn-SA/NGO + PDS system had strong anti-interference ability for TC removal in the presence of anions. Besides, Mn-SA/NGO possessed good reusability and stability. O2•-, •OH, and 1O2 were the main active species for TC degradation, and the TC mineralization reached 85.1%. Density functional theory (DFT) calculations confirmed that the introduction of single atoms Mn could effectively enhance adsorption and activation of PDS. The findings provide a reference for the synthesis of high-performance single-atom catalysts for effective removal of antibiotics.

Impact of Intensive Care Unit Critical Care Management on Patients Diagnosed with Acute Respiratory Distress Syndrome.

Objective: To investigate the impact of critical care management on patients diagnosed with acute respiratory distress syndrome (ARDS) during their stay in intensive care units (ICU). Methods: A total of 62 ARDS patients admitted to the ICU of our hospital between March 2020 and March 2023 were enrolled as research participants. The patients were randomly assigned to either the research group (n=31) receiving critical care management or the control group (n=31) receiving routine care. Key parameters, including the duration of ICU stay, mean hospital length of stay (HLOS), duration of mechanical ventilation, and the incidence of ventilator-associated pneumonia (VAP), were recorded. Additionally, changes in the Self-rating Anxiety/Depression Scale (SAS/SDS), Pittsburgh Sleep Quality Index (PSQI), Acute Physiology and Chronic Health Evaluation II (APACHE), and Clinical Pulmonary Infection Score (CPIS) were assessed before and after the intervention. A self-designed questionnaire was employed to evaluate nursing quality and patient satisfaction. Results: In comparison to the control group, the research group exhibited significantly shorter durations of ICU stay, mean HLOS, and mechanical ventilation, along with a reduced incidence of VAP (P < .05). Moreover, the SAS, SDS, PSQI, APACHE II, and CPIS scores in the research group were lower than those in the control group, while the quality of care and satisfaction scores were notably higher (P < .05). Conclusions: ICU critical care management demonstrates the potential to enhance the rehabilitation of ARDS patients and decrease the incidence of VAP, suggesting its clinical applicability.

More accurate prediction of treatment response than mean apparent diffusion coefficient value in multiple myeloma using whole body MRI histogram analysis.

Aim: To assess baseline histogram parameters from apparent diffusion coefficient (ADC) images in predicting early treatment response in newly diagnosed multiple myeloma (NDMM) patients. Methods: The histogram parameters of lesions in 68 NDMM patients were obtained with the Firevoxel software. The presence of deep response after two cycles of induction was recorded. Results: Some parameters were significantly different between the two groups, for example, ADC 75% in lumbar spine (p = 0.026). No significant difference in mean ADC for any anatomic site was found (all p > 0.05). The combination of ADC 75, ADC 90 and ADC 95% in lumbar spine; ADC skewness and ADC kurtosis in rib achieved a sensitivity of 100% in predicting deep response. Conclusion: Histogram analysis of ADC images can describe NDMM heterogeneity and accurately predict treatment response.

Dual-energy CT may predict post-operative recurrence in early-stage glottic laryngeal cancer: a novel nomogram and risk stratification system.

OBJECTIVES: To establish and validate a predictive model integrating with clinical and dual-energy CT (DECT) variables for individual recurrence-free survival (RFS) prediction in early-stage glottic laryngeal cancer (EGLC) after larynx-preserving surgery. METHODS: This retrospective study included 212 consecutive patients with EGLC who underwent DECT before larynx-preserving surgery between January 2015 and December 2018. Using Cox proportional hazard regression model to determine independent predictors for RFS and presented on a nomogram. The model's performance was assessed using Harrell's concordance index (C-index), time-dependent area under curve (TD-AUC) plot, and calibration curve. A risk stratification system was established using the nomogram with median scores of all cases to divide all patients into two prognostic groups. RESULTS: Recurrence occurred in 39/212 (18.4%) cases. Normalized iodine concentration in arterial (NICAP) and venous phases (NICVP) were verified as significant predictors of RFS in multivariate Cox regression (hazard ratio [HR], 4.2; 95% confidence interval [CI]: 2.3, 7.7, p < .001 and HR, 3.0; 95% CI: 1.5, 5.9, p = .002, respectively). Nomogram based on clinical and DECT variables was better than did only clinical variables. The prediction model proved well-calibrated and had good discriminative ability in the training and validation samples. A risk stratification system was built that could effectively classify EGLC patients into two risk groups. CONCLUSIONS: DECT could provide independent RFS indicators in patients with EGLC, and the nomogram based on DECT and clinical variables was useful in predicting RFS at several time points. KEY POINTS: • Dual-energy CT(DECT) variables can predict recurrence-free survival (RFS) after larynx-preserving surgery in patients with early-stage glottic laryngeal cancer (EGLC). • The model that integrates clinical and DECT variables predicted RFS better than did only clinical variables. • A risk stratification system based on the nomogram could effectively classify EGLC patients into two risk groups.

Prediction of Early Treatment Response in Multiple Myeloma Using MY-RADS Total Burden Score, ADC, and Fat Fraction From Whole-Body MRI: Impact of Anemia on Predictive Performance.

BACKGROUND. The recently released Myeloma Response Assessment and Diagnosis System (MY-RADS) for multiple myeloma (MM) evaluation using whole-body MRI (WB-MRI) describes the total burden score. However, assessment is confounded by red bone marrow hyperplasia in anemia. OBJECTIVE. The purpose of this study is to assess the utility of the MY-RADS total burden score, ADC, and fat fraction (FF) from WB-MRI in predicting early treatment response in patients with newly diagnosed MM and to compare the utility of these measures between patients with and without anemia. METHODS. This retrospective study included 56 patients (40 men, 16 women; mean age, 57.4 ± 9.6 [SD] years) with newly diagnosed MM who underwent baseline WB-MRI including DWI and modified Dixon sequences. Two radiologists recorded total burden score using MY-RADS and measured the ADC and FF of diffuse and focal disease sites. Mean values across sites were derived. Interobserver agreement was evaluated, and the mean assessments of the readers were used for further analyses. Presence of deep response after four cycles of induction chemotherapy was recorded. Patients were classified as having anemia if their hemoglobin level was less than 100 g/L. The utility of WBMRI parameters in predicting deep response was assessed. RESULTS. A total of 24 of 56 patients showed deep response, and 25 of 56 patients had anemia. Interobserver agreement, which was expressed using intraclass correlation coefficients, ranged from 0.95 to 0.99. Among patients without anemia, those with deep response compared with those without deep response had a lower total burden score (9.0 vs 18.0), a lower ADC (0.79 × 10-3 mm2/s vs 1.08 × 10-3 mm2/s), and a higher FF (0.21 vs 0.10) (all p < .001). The combination of these three parameters (optimal cutoffs: ≤ 15 for total burden score, ≤ 0.84 × 10-3 mm2/s for ADC, and > 0.16 for FF) achieved sensitivity of 93.8%, specificity of 93.3%, and accuracy of 93.5% for predicting deep response. In patients with anemia, none of the three parameters were significantly different between patients with and without deep response (all p > .05), and the combination of parameters achieved sensitivity of 56.3%, specificity of 100.0%, and accuracy of 72.0%. CONCLUSION. Low total burden score, low ADC, and high FF from WB-MRI may predict deep response in patients with MM, although only among those without anemia. CLINICAL IMPACT. WB-MRI findings may help guide determination of prognosis and initial treatment selection in MM.

Radiomics of dual-energy computed tomography for predicting progression-free survival in patients with early glottic cancer.

Aim: This study aimed to predict progression-free survival (PFS) in patients with early glottic cancer using radiomic features on dual-energy computed tomography iodine maps. Methods: Radiomic features were extracted from arterial and venous phase iodine maps, and radiomic risk scores were determined by univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator regression with tenfold cross-validation. The Kaplan-Meier method was used to evaluate the association between radiomic risk scores and PFS. Results: Patients were stratified into low-risk and high-risk groups using radiomics, the PFS corresponding rates with statistical significance between the two groups. The high-risk group showed better survival, benefiting from laryngectomy. Conclusion: Radiomics could provide a promising biomarker for predicting the PFS of early glottic cancer patients.

Effects of shrub-grass cover on the hillslope overland flow and soil erosion under simulated rainfall.

Vegetation plays a vital role in regulating hydrological cycle and controlling soil erosion at multiple spatial and temporal scales. Establishing shrub-grass community is one of the widely adopted practices to increase rainfall infiltration and reduce soil erosion in water-limited and highland regions. To understand the effects of such vegetation communities on soil erosion and overland flow under different rainfall regimes at the hillslope scale, we conducted rainfall simulation experiments by setting up parallel plots at fixed slope of 15° including unvegetated (coverage 0%), shrub only (coverage 50%), grass only (coverage 50%), and shrub-grass covered (coverages 25%, 50%, 75%, and 100%) and constant rainfall intensities of 30, 60, and 90 mm h-1 rainfalls lasting 60 min each after the initiation of overland flow. Two native species Lespedeza bicolor and Carex giraldiana, distributed in the soil sampling region were planted on the plots to achieve designed coverages. We found that the overland flow and sediment load from vegetated slopes were reduced by 9%-58% and 27%-98%, respectively, compared with unvegetated slopes while the infiltration rate increased by over 45%. Shrub-grass community reduced the overland flow and sediment yield more significantly than shrub only and grass only treatments with the same coverage of 50% under three rainfall intensities. In addition, the overland flow rate linearly decreased while the mean sediment yield exponentially reduced against the increase in shrub-grass community coverage. Hydrodynamically, shrub-grass communities not only increased the critical hydrodynamic forces for the initiating soil erosion but also increased the resistance coefficient leading to reduce overland flow velocity, stream power, and thus soil erosion from the vegetative slope even under extreme rainfalls. Our research highlights the importance of developing the shrub-grass communities to reduce the quantity and energy of overland flow and control soil erosion on the hillslopes in water-limited and highland regions.

A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism.

Although the dopamine D1-D2 receptor heteromer has emerging physiological relevance and a postulated role in different neuropsychiatric disorders, such as drug addiction, depression, and schizophrenia, there is a need for pharmacological tools that selectively target such receptor complexes in order to analyze their biological and pathophysiological functions. Since no selective antagonists for the D1-D2 heteromer are available, serial deletions and point mutations were used to precisely identify the amino acids involved in an interaction interface between the receptors, residing within the carboxyl tail of the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor heteromer. It was determined that D1 receptor carboxyl tail residues (404)Glu and (405)Glu were critical in mediating the interaction with the D2 receptor. Isolated mutation of these residues in the D1 receptor resulted in the loss of agonist activation of the calcium signaling pathway mediated through the D1-D2 receptor heteromer. The physical interaction between the D1 and D2 receptor could be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small peptide generated from the D1 receptor sequence that contained these amino acids, leading to a switch in G-protein affinities and loss of calcium signaling, resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2 heteromer-disrupting peptide in vivo revealed a pathophysiological role for the D1-D2 heteromer in the modulation of behavioral despair. This peptide may represent a novel pharmacological tool with potential therapeutic benefits in depression treatment.

The impact of hypertension on clinical manifestations of Omicron variant BA.1 infection in adult patients.

COVID-19 caused by Omicron BA.1 has resulted in a global humanitarian crisis. In this COVID-19 pandemic era, hypertension has been receiving increased attention. Omicron BA.1 infection combined with hypertension created a serious public health problem and complicated the treatment and prognosis of COVID-19. The aim of our study was to assess the implications of hypertension for the clinical manifestations of adult patients (APs) infected with Omicron BA.1. This single-center retrospective cohort study enrolled consecutive COVID-19 APs, who were admitted to Tianjin First Central Hospital from 01 August 2022 to 30 November 2022. All included APs were divided into two groups: hypertension and non-hypertension group. The APs' baseline demographic, laboratory, clinical, and radiological characteristics were collected and analyzed. Of 512 APs admitted with PCR proven COVID-19, 161 (31.45%) APs had comorbid hypertension. Hypertension APs have older age, higher body mass index, lower Ct-values of the viral target genes at admission, and longer hospital stay than non-hypertension APs. Furthermore, hypertension aggravates the clinical classification, impairs liver, kidney, and myocardium function, and abnormalizes the coagulation system in Omicron BA.1- infected APs. Moreover, hypertension elevates inflammation levels and lung lesion involvement while weakened virus-specific IgM level in APs with Omicron BA.1 infection. Hypertension APs tend to have worse clinical conditions at baseline than those non-hypertension APs. This study indicates that hypertension is a contributor to the poor clinical manifestations of Omicron BA.1-infected APs and supports that steps to control blood pressure should be a vital consideration for reducing the burden of Omicron BA.1 infection in hypertension individuals. IMPORTANCE: This study provided inclusive insight regarding the relationship between hypertension and Omicron BA.1 infection and supported that hypertension was an adverse factor for COVID-19 APs. In conclusion, this study showed that hypertension was considered to be associated with severe conditions, and a contributor to poor clinical manifestations. Proper medical management of hypertension patients is an imperative step in mitigating the severity of Omicron BA.1 variant infection.

Geniposide ameliorates atherosclerosis by restoring lipophagy via suppressing PARP1/PI3K/AKT signaling pathway.

BACKGROUND: Atherosclerosis (AS) is the leading cause of global death, which manifests as arterial lipid stack and plaque formation. Geniposide is an iridoid glycoside extract from Gardenia jasminoides J.Ellis that ameliorates AS by mediating autophagy. However, how Geniposide regulates autophagy and treats AS remains unclear. PURPOSE: To evaluate the efficacy and mechanism of Geniposide in treating AS. STUDY DESIGN AND METHODS: Geniposide was administered to high-fat diet-fed ApoE-/- mice and oxidized low-density lipoprotein-incubated primary vascular smooth muscle cells (VSMCs). AS was evaluated with arterial lipid stack, plaque progression, and collagen loss in the artery. Foam cell formation was detected by lipid accumulation, inflammation, apoptosis, and the expression of foam cell markers. The mechanism of Geniposide in treating AS was assessed using network pharmacology. Lipophagy was measured by lysosomal activity, expression of lipophagy markers, and the co-localization of lipids and lipophagy markers. The effects of lipophagy were blocked using Chloroquine. The role of PARP1 was assessed by Olaparib (a PARP1 inhibitor) intervention and PARP1 overexpression. RESULTS: In vivo, Geniposide reversed high-fat diet-induced hyperlipidemia, plaque progression, and inflammation. In vitro, Geniposide inhibited VSMC-derived foam cell formation by suppressing lipid stack, apoptosis, and the expressions of foam cell markers. Network pharmacological analysis and in vitro validation suggested that Geniposide treated AS by enhancing lipophagy via suppressing the PI3K/AKT signaling pathway. The benefits of Geniposide in alleviating AS were offset by Chloroquine in vivo and in vitro. Inhibiting PARP1 using Olaparib promoted lipophagy and alleviated AS progression, while PARP1 overexpression exacerbated foam cell formation and lipophagy blockage. The above effects of PARP1 were weakened by PI3K inhibitor LY294002. PARP1 also inhibited the combination of the ABCG1 and PLIN1. CONCLUSION: Geniposide alleviated AS by restoring PARP1/PI3K/AKT signaling pathway-suppressed lipophagy. This study is the first to present the lipophagy-inducing effect of Geniposide and the binding of ABCG1 and PLIN1 inhibited by PARP1.

Construction of a 3-year risk prediction model for developing diabetes in patients with pre-diabetes.

Introduction: To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM. Methods: Subjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted. Results: Comparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P<0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P>0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P<0.05), while HDL-C was a protective factor (P<0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model. Conclusions: The risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration.

D5 dopamine receptor carboxyl tail involved in D5-D2 heteromer formation.

We have demonstrated that D(5) and D(2) dopamine receptors exist as heteromers in cells, and determined these receptor interact through amino acids in the cytoplasmic regions of each receptor. Specifically involved in heteromer formation we identified in the carboxyl tail of the D(5) receptor three adjacent glutamic acid residues, and in intracellular loop 3 of the D(2) receptor two adjacent arginine residues. Any pairing of these three D(5) receptor glutamic acids were sufficient for heteromer formation. These identified residues in D(5) and D(2) receptors are oppositely charged and likely interact by electrostatic interactions.

Discovery of 2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as novel PKM2 activators.

The M2 isoform of pyruvate kinase is an emerging target for antitumor therapy. In this letter, we describe the discovery of 2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as potent and selective PKM2 activators which were found to have a novel binding mode. The original lead identified from high throughput screening was optimized into an efficient series via computer-aided structure-based drug design. Both a representative compound from this series and an activator described in the literature were used as molecular tools to probe the biological effects of PKM2 activation on cancer cells. Our results suggested that PKM2 activation alone is not sufficient to alter cancer cell metabolism.

Developing self-floating N-defective graphitic carbon nitride photocatalyst for efficient photodegradation of Microcystin-LR under visible light.

The frequent occurrence of algal blooms in water bodies leads to a significant accumulation of microcystin-LR (MC-LR). In this study, we developed a porous foam-like self-floating N-deficient g-C3N4 (SFGN) photocatalyst for efficient photocatalytic degradation of MC-LR. Both the characterization results and DFT calculations indicate that the surface defects and floating state of SFGN synergistically enhance light harvesting and photogenerated carrier migration rate. The photocatalytic process achieved a nearly 100 % removal rate of MC-LR within 90 min, while the self-floating state of SFGN maintained good mechanical strength. ESR and radical capture experiments revealed that the primary active species responsible for the photocatalytic process was OH. This finding confirmed that the fragmentation of MC-LR occurs as a result of OH attacking the MC-LR ring. LC-MS analysis indicated that majority of the MC-LR molecules were mineralized into small molecules, allowing us to infer possible degradation pathways. Furthermore, after four consecutive cycles, SFGN exhibited remarkable reusability and stability, highlighting the potential of floating photocatalysis as a promising technique for MC-LR degradation.

Effects of 5-HT2C receptor stimulation in male mice on behaviour and Fos expression: Feeding, reward and impulsivity.

Serotonin modulates many motivated behaviours via multiple receptor subtypes. Agonists at 5-HT2C receptors have potential for treating behavioural problems associated with obesity and drug use. In this work we examined the impact of the 5-HT2C receptor agonist lorcaserin on several motivated behaviours related to feeding, reward and waiting impulsivity, and on neuronal activation in key brain areas mediating those behaviours. In male C57BL/6J mice effects of lorcaserin (0.2, 1 and 5 mg/kg) were examined on feeding, and on operant responding for a palatable reward. Feeding was reduced only at 5 mg/kg, whereas operant responding was reduced at 1 mg/kg. At a much lower dose range lorcaserin 0.05-0.2 mg/kg also reduced impulsive behaviour measured as premature responding in the 5-choice serial reaction time (5-CSRT) test, without affecting attention or ability to perform the task. Lorcaserin induced Fos expression in brain regions related to feeding (paraventricular nucleus and arcuate nucleus), reward (ventral tegmental area), and impulsivity (medial prefrontal cortex, VTA) although these effects did not show the same differential sensitivity to lorcaserin as the behavioural measures. These results indicate a broad profile of action of 5-HT2C receptor stimulation on brain circuitry and on motivated behaviours, but with clear evidence of differential sensitivity across behavioural domains. This is exemplified by the fact that impulsive behaviour was reduced at a much lower dose range than was feeding behaviour. Along with previous work, and some clinical observations, this work supports the idea that 5-HT2C agonists may be useful for behavioural problems associated with impulsivity.

Two amino acids in each of D1 and D2 dopamine receptor cytoplasmic regions are involved in D1-D2 heteromer formation.

D(1) and D(2) dopamine receptors exist as heteromers in cells and brain tissue and are dynamically regulated and separated by agonist concentrations at the cell surface. We determined that these receptor pairs interact primarily through discrete amino acids in the cytoplasmic regions of each receptor, with no evidence of any D(1)-D(2) receptor transmembrane interaction found. Specifically involved in heteromer formation we identified, in intracellular loop 3 of the D(2) receptor, two adjacent arginine residues. Substitution of one of the arginine pair prevented heteromer formation. Also involved in heteromer formation we identified, in the carboxyl tail of the D(1) receptor, two adjacent glutamic acid residues. Substitution of one of the glutamic acid pair prevented heteromer formation. These amino acid pairs in D(1) and D(2) receptors are oppositely charged, and presumably interact directly by electrostatic interactions.

Disruption of the mu-delta opioid receptor heteromer.

The crystal structure of the mu and kappa opioid receptors has revealed dimeric structural arrangements. Mu-delta receptors heteromers also exist and we have identified discrete cytoplasmic regions in each receptor required for oligomer formation. In the carboxyl tail of the delta receptor we identified three glycine residues (-GGG), substitution of any of these residues prevented heteromer formation. In intracellular loop 3 of both mu and delta receptors we identified three residues (-SVR), substitution of any of these residues prevented heteromer formation.

Influence of root distribution patterns on soil dynamic characteristics.

Slopes along the highway and railway routes are subjected to not only static loads but also dynamic loads generated by vehicles and trains. The induced excessive deformation potentially poses a threat to slope stability. In terms of the extensive application of ecological slope protection, plants play a critical role in slope stability, as the roots can enhance the shear strength of the soil. This study aims to investigate the influence of different root distribution patterns on the dynamic characteristics induced by cyclic loading. By conducting a group of dynamic triaxial tests, the results indicate that the root system can significantly enhance the liquefaction resistance of the soil when the soil is subjected to lower dynamic loads, and the cross arrangement has a better-reinforced effect than the mixed arrangement. The reinforced effect was not obvious when the soil was subjected to a dynamic load with a larger stress amplitude. In addition, based on the validation of the seed model, a new pore water pressure development model was proposed according to the test results. Overall, the research provides a new model and some innovative observations to better understand the dynamic behavior of root-reinforced soil.

Effects of pimavanserin and lorcaserin on alcohol self-administration and reinstatement in male and female rats.

The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) modulates fundamental motivational processes, and the neurochemical and behavioural effects of drugs of abuse. Recently, attention has focused on the role of 5-HT acting via 5-HT2A and 5-HT2C receptor sub-types in this regard. We examined the impact of manipulating 5-HT2A and 5-HT2C receptor mediated function on several aspects of alcohol self-administration and alcohol-seeking behaviour in male and female rats. Specifically, experiments investigated the effect of the 5-HT2A inverse agonist/antagonist pimavanserin, and the 5-HT2C receptor agonist lorcaserin on these behaviours. In male and female rats trained to respond for alcohol reinforcement on fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement pimavanserin (0.3, 1 and 3 mg/kg) had no consistent effect on responding. Lorcaserin (0.25, 0.5 and 1 mg/kg) reduced these behaviours in both sexes. Following extinction of responding for alcohol, alcohol-seeking was reinstated by cues previously paired with alcohol. Pimavanserin (1 mg/kg) and lorcaserin (0.5 mg/kg) significantly reduced this reinstatement. In a two-bottle 24 h intermittent access procedure pimavanserin had no significant effects, but lorcaserin reduced alcohol consumption in both sexes at 1, 4 and 24 h after access to alcohol was allowed. Finally, as determined using in vivo microdialysis, alcohol increased, and lorcaserin (0.5 mg/kg) reduced, extracellular levels of DA in the NAc in male rats. In rats treated with lorcaserin prior to alcohol injection the net effect was that DA levels were not changed compared to those measured in control rats. These results suggest that blocking 5-HT2A receptor activity has a very limited action to reduce alcohol-seeking. Activating 5-HT2C receptors had a broader behavioural profile to reduce alcohol self-administration, alcohol drinking and alcohol seeking. These effects may partly result from a blunting of the effect of alcohol on mesolimbic DA release.

Numerical Simulation of the Shear Capacity of a GFRP-Strengthened Natural Bamboo-Bolt Composite Joint.

As an ecological green building material, natural bamboo has many advantages such as a light weight, high strength, and short growth cycle. Natural bamboo is widely used in landscape architecture and fabricated structures. However, in bamboo building structures, the most common bolted joints often appear cleaved along the grain. In this paper, glass fiber-reinforced polymer (GFRP) is designed to wrap and improve the shear capacity of natural bamboo-bolt composite joints. According to the corresponding material parameters, the finite element model of composite joints is established, and the key influencing variables of the bearing capacity, namely the bolt diameter, bamboo tube outer diameter, and screw end distance, are analyzed. In addition, according to the European analytical yield model of bolted connections, the analytical calculation method of the bearing capacity is proposed and compared with the experimental and simulated values. The results showed that the numerical model and the modified analytical model can suitably describe the bearing capacity of composite joints, and a higher bolt diameter, along with the bamboo outer diameter, will lead to a higher ultimate load of the composite joints. Moreover, the bearing capacity of composite joints has no obvious relationship with the end spacing.