Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament

A common variant (rs53576) of the OXTR gene has been implicated in a number of socio-emotional phenotypes, such as anxiety-related behavior. Previous studies have demonstrated that A-allele carriers have higher levels of physiological and dispositional stress reactivity and depressive symptomatology compared to those with the GG genotype, but the mediating neural mechanisms remain poorly understood. We combined voxel-based morphometry and resting-state functional connectivity analyses in a large cohort of healthy young Chinese Han individuals to test the hypothesis that the OXTR gene polymorphism influences an anxiety-related temperamental trait, as assessed by the harm avoidance subscale from the Tridimensional Personality Questionnaire via modulating the gray matter volume and resting-state functional connectivity of the brain, especially the limbic system. We revealed that female subjects with the AA genotype showed increased harm avoidance scores relative to G-carrier females. We also found that, compared to female individuals with the GG/GA genotype, female individuals with the AA genotype exhibited significantly smaller amygdala volumes bilaterally (especially the centromedial subregion), with a trend of allele-load-dependence. Compared to female individuals with the GG/GA genotype, female subjects with the AA genotype demonstrated reduced resting-state functional coupling between the prefrontal cortex and amygdala bilaterally, also with an allele-load-dependent trend. Furthermore, the magnitude of prefrontal-amygdala coupling in the left hemisphere was positively correlated with harm avoidance scores in female subjects. Our findings highlight a possible neural pathway by which a naturally occurring variation of the OXTR gene may affect an anxiety-related temperamental trait in female subjects by modulating prefrontal-amygdala functional connectivity

Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments

The human telomeric G-quadruplex (G4) is an attractive target for developing anticancer drugs. Natural products protoberberine alkaloids are known to bind human telomeric G4 and inhibit telomerase. Among several structurally similar protoberberine alkaloids, epiberberine (EPI) shows the greatest specificity in recognizing the human telomeric G4 over duplex DNA and other G4s. Recently, NMR study revealed that EPI recognizes specifically the hybrid-2 form human telomeric G4 by inducing large rearrangements in the 50-flanking segment and loop regions to form a highly extensive four-layered binding pocket. Using the NMR structure of the EPI-human telomeric G4 complex, here we perform molecular dynamics free energy calculations to elucidate the ligand selectivity in the recognition of protoberberines by the human telomeric G4. The MM-PB(GB)SA (molecular mechanics-Poisson Boltzmann/Generalized Born) Surface Area) binding free energies calculated using the Amber force fields bsc0 and OL15 correlate well with the NMR titration and binding affinity measurements, with both calculations correctly identifying the EPI as the strongest binder to the hybrid-2 telomeric G4 wtTel26. The results demonstrated that accounting for the conformational flexibility of the DNA-ligand complexes is crucially important for explaining the ligand selectivity of the human telomeric G4. While the MD-simulated (molecular dynamics) structures of the G-quadruplex-alkaloid complexes help rationalize why the EPI-G4 interactions are optimal compared with the other protoberberines, structural deviations from the NMR structure near the binding site are observed in the MD simulations. We have also performed binding free energy calculation using the more rigorous double decoupling method (DDM); however, the results correlate less well with the experimental trend, likely due to the difficulty of adequately sampling the very large conformational reorganization in the G4 induced by the protoberberine binding

The Time Course Effects of Electroacupuncture on Promoting Skeletal Muscle Regeneration and Inhibiting Excessive Fibrosis after Contusion in Rabbits

The aim of this study was to investigate the longitudinal effects of electroacupuncture (EA) on Zusanli (ST36) and Ashi acupoints in promoting skeletal muscle regeneration and inhibiting excessive fibrosis after contusion in rabbits. Sixty rabbits were randomly divided into four groups: normal, contusion, EA, and recombinant human insulin-like growth factor-I (rhIGF-I). An acute skeletal muscle contusion was produced on the right gastrocnemius (GM) by an instrument-based drop-mass technique. EA was performed for 15 minutes every two days with 0.4 mA (2 Hz), and GM injections were executed with rhIGF-I (0.25 mL once a week). Rabbits treated with EA had a higher T-SOD and T-AOC serum activities and lower MDA serum level, the blood perfusion of which was also significantly higher. In the EA group, the diameter of the myofibril was uniform and the arrangement was regular, contrary to the contusion group. The number and diameter of regenerative myofibers and MHC expression were increased in the EA group. EA treatment significantly decreased fibrosis formation and reduced both GDF-8 and p-Smad2/3 expressions in injured muscle. Our data indicate that EA may promote myofiber regeneration and reduce excessive fibrosis by improving blood flow and antioxidant capacities. Additionally, EA may regulate signaling factor expression after contusion

Comparative study on distributed generation trading mechanisms in the UK and China

Abstract: The market penetration of distributed generation (DG), particularly for that from renewables, has significantly increased in recent years. This trend will continue with the low‐carbon transition of electric power systems, as a part of global efforts to combat climate change. Appropriate trading mechanisms are of great importance for incentivizing the investment in and coordinated operation of DG. The UK and China both have ambitious decarbonization agendas with particular emphasis on the electricity market design. Nevertheless, the UK and China have distinguishing features in electricity market design, particularly in the trading mechanisms for DG. This paper presents a thorough review of DG trading policies and arrangements in both countries, including market structures, connection classifications, economic benefits and practical issues. The strengths, weaknesses, opportunity, and threats‐political, economical, social and technological (SWOT‐PEST) model features of the mechanisms in both countries were qualitatively identified and compared. A quantitative comparison was conducted between the trading arrangements in the UK and China, with the economic benefits analysed and the implications revealed. Finally, the directions for developing and improving DG trading mechanisms were suggested based on the comparative analysis. The practical experiences of the UK and China can be extended to other countries across the globe

Exploring biochar and fishpond sediments potential to change soil phosphorus fractions and availability

Phosphorus (P) availability in soil is paradoxical, with a significant portion of applied P accumulating in the soil, potentially affecting plant production. The impact of biochar (BR) and fishpond sediments (FPS) as fertilizers on P fixation remains unclear. This study aimed to determine the optimal ratio of BR, modified biochar (MBR), and FPS as fertilizer replacements. A pot experiment with maize evaluated the transformation of P into inorganic (Pi) and organic (Po) fractions and their contribution to P uptake. Different percentages of FPS, BR, and MBR were applied as treatments (T1–T7), T1 [(0.0)], T2 [FPS (25.0%)], T3 [FPS (25.0%) + BR (1%)], T [FPS (25%) +MBR (3%)], T5 [FPS (35%)], T6 [FPS (35%) +BR (1%)], and T7 [FPS (35%) + MBR (1%)]. Using the modified Hedley method and the Tiessen and Moir fractionation scheme, P fractions were determined. Results showed that various rates of MBR, BR, and FPS significantly increased labile and moderately labile P fractions (NaHCO3-Pi, NaHCO3-Po, HClD-Pi, and HClC-Pi) and residual P fractions compared with the control (T1). Positive correlations were observed between P uptake, phosphatase enzyme activity, and NaHCO3-Pi. Maximum P uptake and phosphatase activity were observed in T6 and T7 treatments. The addition of BR, MBR, and FPS increased Po fractions. Unlike the decline in NaOH-Po fraction, NaHCO3-Po and HClc-Po fractions increased. All Pi fractions, particularly apatite (HClD-Pi), increased across the T1–T7 treatments. HClD-Pi was the largest contributor to total P (40.7%) and can convert into accessible P over time. The T5 treatment showed a 0.88% rise in residual P. HClD-Pi and residual P fractions positively correlated with P uptake, phosphatase activity, NaOH-Pi, and NaOH-Po moderately available fractions. Regression analysis revealed that higher concentrations of metals such as Ca, Zn, and Cr significantly decreased labile organic and inorganic P fractions (NaHCO3-Pi, R2 = 0.13, 0.36, 0.09) and their availability (NaHCO3-Po, R2 = 0.01, 0.03, 0.25). Excessive solo BR amendments did not consistently increase P availability, but optimal simple and MBR increased residual P contents in moderately labile and labile forms (including NaOH-Pi, NaHCO3-Pi, and HClD-Pi). Overall, our findings suggest that the co-addition of BR and FPS can enhance soil P availability via increasing the activity of phosphatase enzyme, thereby enhancing plant P uptake and use efficiency, which eventually maintains the provision of ecosystem functions and services

Eff ect of a comprehensive programme to provide universal access to care for sputum-smear-positive multidrugresistant tuberculosis in China: a before-and-after study

Background China has a quarter of all patients with multidrug-resistant tuberculosis (MDRTB) worldwide, but less than 5% are in quality treatment programmes. In a before-and-after study we aimed to assess the eff ect of a comprehensive programme to provide universal access to diagnosis, treatment, and follow-up for MDRTB in four Chinese cities (population 18 million). Methods We designated city-level hospitals in each city to diagnose and treat MDRTB. All patients with smear-positive pulmonary tuberculosis diagnosed in Center for Disease Control (CDC) clinics and hospitals were tested for MDRTB with molecular and conventional drug susceptibility tests. Patients were treated with a 24 month treatment package for MDRTB based on WHO guidelines. Outpatients were referred to the CDC for directly observed therapy. We capped total treatment package cost at US$4644. Insurance reimbursement and project subsidies limited patients’ expenses to 10 (2011) to those from a retrospective survey of all patients with MDRTB diagnosed in the same cities during a baseline period (2006–09). Findings 243 patients were diagnosed with MDRTB or rifampicin-resistant tuberculosis during the 12 month programme period compared with 92 patients (equivalent to 24 per year) during the baseline period. 172 (71 243 individuals were enrolled in the programme. Time from specimen collection for resistance testing to treatment initiation decreased by 90 started on appropriate drug regimen increased 2·7 times (from nine [35 172), and follow-up by the CDC after initial hospitalisation increased 24 times (from one [4 163 [99 increased ten times (from two [8 programme period had negative cultures or clinical–radiographic improvement. Patients’ expenses for hospital admission after MDRTB diagnosis decreased by 78$796 to $174), reducing the ratio of patients’ expenses to annual household income from 17·6% to 3·5% (p<0·0001 for all comparisons between baseline and programme periods). However, 36 (15%) patients did not start or had to discontinue treatment in the programme period because of fi nancial diffi culties. Interpretation This comprehensive programme substantially increased access to diagnosis, quality treatment, and aff ordable treatment for MDRTB. The programme could help China to achieve universal access to MDRTB care but greater fi nancial risk protection for patients is needed