Cumulative Amount Research Articles

Silicone Oil Tamponade Removal: Which Technique Is More Effective? An X-Ray Photoemission Spectroscopy Study.

To compare the efficacy of two surgical techniques used to remove silicone oil (SiO) emulsion tamponade after pars plana vitrectomy: triple air-fluid exchange (AFX) and balanced salt solution lavage (BSSL). X-ray photoemission spectroscopy measured silicon content of the dry residue of fluid samples taken during AFX and BSSL. Ten patients underwent AFX and five BSSL. Three fluid samples were taken per patient, and the dry residue of 10 drops per sample were analyzed. A fluid sample from a patient who never received SiO tamponade was also analyzed to set a "blank" reference sample. Patients' demographics showed no significant difference. Sample 1 of the two groups contained comparable silicon content while samples 2 and 3 of the AFX group contained significantly more silicon than that of the BSSL group (15.0 ± 0.1 and 12.0 ± 0.9 for the AFX group vs. 10.7 ± 1.4 and 5.2 ± 0.6 for the BSSL group, respectively; P < 0.05). The cumulative amount of silicon in the three successive samples was also significantly higher for the AFX group (42.3 ± 1.6 vs. 32 ± 2; P < 0.0001). The average silicon content ratio of consecutive samples was significantly higher for the AFX group compared to the BSSL group (0.90 ± 0.01 vs. 0.58 ± 0.06; P = 0.006). Triple AFX removed more silicon than triple lavage. The eye wall actively interacts with silicon emulsion retaining silicon content rather than behaving as a neutral container. Triple air-fluid exchange removed more silicon than BSS lavage. Neither technique behaved as a well-mixed box dilution, suggesting the eye walls actively retain emulsion and a dynamic equilibrium is established between silicon dispersion and the eye wall surface.

Cocrystallization of 5-fluorouracil with gallic acid: A novel 5-fluorouracil cocrystal displaying synergistic anti-tumor activity both in oral and intraperitoneal injection administration

Gallic acid (GA) is a naturally occurring polyphenolic compound exhibiting anti-tumor activity. To clarify the capability of GA in optimizing the in vitro/in vivo properties of the first line anti-tumor drug 5-fluorouracil (5-FU) and achieve synergistically enhanced anti-tumor activity, a novel cocrystal hydrate of 5-FU-GA-H2O was successfully screened and characterized based on various spectroscopic and experimental analysis including Fourier transform infrared spectroscopy (FT-IR), Raman spectra (Raman), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric (TG) and scanning electric microscope (SEM) techniques. The results suggested the existence of hydrogen bonding interactions between C=O group of 5-FU and O–H group of GA. Although the dissolution rate and solubility of 5-FU-GA-H2O cocrystal were slowed and lowered compared with that of 5-FU, respectively, the membrane permeability was enhanced for cocrystal compared with that of intact 5-FU and physical mixture (PM) of 5-FU and GA. For the cocrystal, the cumulative amount per unit area of permeated 5-FU in the first 10 h was 2.56 and 9.97 times of that of pure 5-FU and PM, respectively, in the case that transmembrane behavior of 5-FU depended on the type of solution from which the powder was dissolved. Meanwhile, improvement on oral bioavailability by co-crystallization was observed; AUC0-t of cocrystal was 2.78-fold higher than that of 5-FU. Furthermore, the cocrystal displayed a superior cytotoxic activity on 4T1 mouse breast cancer cells compared with pure 5-FU and even the PM. It was confirmed that the cocrystal solution induced higher autophagic flux than those of 5-FU and PM in 4T1 cell, suggesting that autophagy rather than apoptosis mainly mediated cell death. The obvious difference of tumor inhibition activity between PM and cocrystal in intraperitoneal injection administration indicated that some of the interactions formed in the solid cocrystal could retain in solution in some way. Benefiting from synergistic cytotoxicity, drug efficacy in vivo was enhanced through injection administration of solution from which cocrystal was dissolved.

Understanding the carbon dioxide removal range in 1.5 °C compatible and high overshoot pathways

Carbon dioxide removal (CDR) features prominently in the 1.5 °C compatible and high overshoot pathways in the IPCC’s Sixth Assessment Report (AR6, WGIII). However, the amount of CDR varies considerably among scenarios. We analyze the range in CDR volumes in AR6 WGIII pathways by exploring relationships between variables as potential driving forces, focusing on CDR in 2050 and scenario properties linked to reaching net-zero CO2. It is also shown how the relative and absolute contribution of CDR to total mitigation up until reaching net-zero CO2 substantially differs across scenarios. The volumes of CDR in 2050 and 2100 and the cumulative amount throughout the 21st century were most strongly correlated to the degree to which CO2 emissions are reduced as a means of reaching net-zero CO2. CDR in 2050 is also substantially correlated to the timing of net-zero CO2. The robustness of the analyzed relationships was evaluated by comparing different scenario filtering and data-cleaning approaches. Beyond filtering and cleaning, additional factors that influence CDR deployment in scenarios, such as discount rates, carbon price trajectories, and scenario design choices, were discussed.

Yuhong ointment ameliorates inflammatory responses and wound healing in scalded mice.

Yuhong ointment (YHO) is famous for its efficacy in clearing away heat and dampness, reducing swelling and relieving pain, and it has been used for more than 600 years. Scalding damages the skin's defense function, resulting in a large number of necrotic tissues and cells on the wound surface, which favors bacterial growth and inflammation. If the inflammation reaction is not controlled on time, it may lead to reduced immunity and cause complications such as infection. Yuhong ointment can promote wound healing in scalded mice, but its potential pharmacological mechanism is still unclear. This study focused on identifying the active ingredients of YHO and on investigating the performance of YHO in terms of anti-inflammatory activity and scald wound healing activity. High-performance liquid chromatography (HPLC) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) were performed to identify the active ingredients of YHO. The performance of transdermal delivery of YHO was studied via HPLC for analyzing the ingredients of the exposed skin liquid of mice. Enzyme-linked immunosorbent assay (ELISA) analysis, immunohistochemistry, and real-time fluorescence quantitative PCR (qRT-PCR) were used to investigate the anti-inflammatory and scald wound healing activity of YHO. A total of 41 components of YHO were identified via HPLC and HPLC-MS for the first time. In the transdermal delivery experiment, the cumulative amounts of chlorogenic acid, sesamol, ferulic acid, and L-shikonin were calculated to be 342.28, 567.89, 384.54, and 528.67 μg/cm2, respectively. Pharmacological activity experiments indicated that these four kinds of drugs exhibited different degrees of therapeutic effects on scald. Specifically, YHO high-dose (YHO-H) group showed better therapeutic ability (P < 0.01) than FN and MB group. Furthermore, the immune function of the YHO group was enhanced due to the continuous increment of the levels of Hydroxyproline (HYP), Immunoglobulin G (IgG), and vascular endothelial growth factor (VEGF) and simultaneous decrement of the levels of TNF-α, TNF-β, IL-10, and IL-6 in the skin wound. Histological results showed that the thickening of skin tissue was alleviated after treatment with YHO. Moreover, the expression of substance P (SP), calcitonin gene related peptide (CGRP) and transient receptor potential vanilloid-1 (TRPV1) was inhibited, and the expression of VEGF was promoted by YHO (P < 0.01). The qRT-PCR test results indicated that the YHO group exhibited better inhibitory effect on interleukin 6 (IL-6), interleukin 10 (IL-10), transforming growth factor-beta (TGF-β), and Smad-3 mRNA expression levels than the other groups. In this work, the active ingredients of YHO were identified via HPLC and HPLC-MS analysis. Importantly, YHO showed great advantages in transdermal delivery and scald wound healing, which can be attributed to the both anti-inflammatory and tissue regeneration mechanisms. Therefore, this work not only identified the active ingredients of YHO but also revealed the potential pharmacological mechanism of YHO for the healing of scald.

Fibrin clot and Leukocyte-rich platelet-rich fibrin show similar release kinetics and amount of growth factors: a pilot study

BackgroundIn knee arthroscopic surgery, fibrin clot (FC) and leukocyte-rich platelet-rich fibrin (L-PRF) may be used in augmentation for meniscal repair. Studies have investigated growth factors released from FC and L-PRF; however, it is difficult to compare FC and L-PRF between different studies. Direct comparison of growth factors that may support meniscal healing released from FC and L-PRF may be beneficial in deciding whether to use FC or L-PRF. If no significant difference is seen, the surgeon may decide to use FC which is easier to prepare compared to L-PRF. The purpose of this pilot study is to investigate the release amount and pattern of basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) from FC and L-PRF.MethodTwenty milliliters (ml) of whole blood was collected from each of the four volunteers. Ten milliliters of whole blood was allocated for preparation of FC and 10 ml for L-PRF. FC and L-PRF were separately placed in 5 ml of culture media. Five milliliters of the culture media was sampled and refilled at 15 min, 1 day, 3 days, 1 week and 2 weeks. The collected culture was used to quantify bFGF, PDGF-AB, TGF-β1, VEGF, and SDF-1 release by Enzyme-linked immune-sorbent assay (ELISA). Mann–Whitney U test was performed to assess significance of differences in amount of each growth factor released between FC and L-PRF. Significance was accepted at P value less than 0.05.ResultsAt two weeks, the cumulative release of TGF-β1 was the highest among all the growth factors in both FC and L-PRF (FC:19,738.21 pg/ml, L-PRF: 16,229.79 pg/ml). PDGF-AB (FC: 2328 pg/ml, L-PRF 1513.57 pg/ml) had the second largest amount, followed by VEGF (FC: 702.06 pg/ml, L-PRF 595.99 pg/ml) and bFGF (FC: 23.48 pg/ml, L-PRF 18.2 pg/ml), which order was also common in both FC and L-PRF. No significant difference in final release amount and pattern was seen between FC and L-PRF.ConclusionThe current pilot study showed that cumulative release amount and release pattern of PDGF-AB, VEGF, TGF-β1, and bFGF did not significantly differ between FC and L-PRF during the two weeks of observation.

Preparation and Evaluation of Niosomal Transdermal Patch of Clozapine

Niosomes are the non-ionic surfactant vesicles obtained on hydration of synthetic non-ionic surfactants. These are the promising vehicles for effective transdermal drug delivery. The present research work was aimed to develop niosomal-based transdermal Clozapine patch containing a stable formulation with improved drug permeation. Niosomes were prepared by solvent casting method. All the formulations were evaluated for vesicle size, zeta potential and percent entrapment efficiency. All the patches were then characterized for thickness, folding endurance, drug content determination, Flatness, and in vitro permeation studies. F3 formulation having optimum vesicle size (2.6m), highest zeta potential (-32.56mV) and maximum percent entrapment efficiency (98.09%) was selected as optimized formulation. The transdermal patch was prepared using solvent casting method from the optimised niosomes formulation F3 formulation. The prepared optimised niosomes F3 formulation were loaded into the patch formulation. Patches loaded with niosomes (F3NT3) showed 95.78 % cumulative amount of drug permeated. The optimized formulation (F3NT3) followed first order release kinetics.

Grassland songbird abundance is influenced more strongly by individual types of disturbances than cumulative disturbances associated with natural gas extraction.

Grassland birds have undergone widespread global population declines due to loss and degradation of native grasslands. Activities associated with non-renewable energy derived from oil and natural gas extraction have substantially increased on grasslands. The cumulative disturbance generated by natural gas development creates a network of non-linear (e.g., bare ground and exotic plant species) and linear (e.g., roads, trails, pipelines) features that may degrade habitat quality for grassland species. We quantified grassland songbird abundance in two areas of southwestern Saskatchewan, Canada, to determine whether variation in abundance 1) depended on the type and amount of disturbance at two spatial extents, and 2) was more affected by the cumulative impacts of natural gas development than any single type of disturbance. We found that specific types of disturbances impacted the abundance of most species to varying degrees. The cover of different types of linear disturbance had the strongest effect on the most species. Natural gas disturbance within 450 m of point counts was more influential than disturbance within 200 m for nearly all species in both areas. Only Savannah sparrow (Passerculus sandwichensis) abundance was most strongly influenced by the cumulative amount of disturbance with abundance decreasing with increased disturbance. Overall, we detected few consistent patterns among species, or within species between our two study areas. Our results indicated that the impact of natural gas infrastructure can extend beyond the local influences associated with well sites and that relatively small amounts of disturbance (<2%) may impact grassland songbird abundance. We recommend that researchers use caution when studying well-density effects or combining individual types of disturbance without understanding the separate effects each type of disturbance has on the species or community of interest. Not doing so may lead to investing resources into management practices that do not have the greatest possible benefit for grassland songbirds.

Transdermal Delivery of Insulin Using Combination of Iontophoresis and Deep Eutectic Solvents as Chemical Penetration Enhancers: In Vitro and in Vivo Evaluations

A serious challenge in transdermal iontophoresis (IP) delivery of insulin (INS) is the low permeability of the drug across the skin. In this paper, we introduced deep eutectic solvent (DESs) as novel chemical penetration enhancers (CPEs) for transdermal IP of INS across rat skin, both in vitro and in vivo. Three different DESs based on choline chloride (ChCl), namely, ChCl/UR (ChCl and urea), ChCl/GLY (ChCl and glycerol), and ChCl/EG (ChCl and ethylene glycol) in the 1:2 molar ratios have been prepared. To evaluate the capability of studied DESs as CPEs for IP delivery of INS, the rat skin sample was treated with each DES. The effects of different experimental parameters (current density, formulation pH, INS concentration, NaCl concentration, and treatment time) on the in vitro transdermal iontophoretic delivery of INS were investigated. The in vitro permeation studies exhibited that INS was easily delivered employing ChCl/EG, and ChCl/GLY treatments, compared with ChCl/UR: the cumulative amount of permeated INS at the end of the experiment (Q24h) was found to be 131.0, 89.4, and 29.6 µg cm−2 in the presence of ChCl/EG, ChCl/GLY, and ChCl/UR, respectively. The differences in Q24h values of INS are due to the different capabilities of the studied DESs to treat the epidermis layer of skin. In vivo experiments revealed that the blood glucose level in diabetic rats could be decreased using ChCl/EG, and ChCl/GLY as novel CPEs in the IP delivery of INS. The presented work will open new doors towards searching for novel CPEs in the development of transdermal IP of INS.

Dose adjustment not required for contezolid in patients with moderate hepatic impairment based on pharmacokinetic/pharmacodynamic analysis.

Objective: Contezolid is an oxazolidinone antimicrobial agent newly approved for treatment of Gram-positive bacterial infections. It is primarily metabolized by the liver. This study aimed to assess whether it is required to adjust the dose of contezolid in patients with moderate hepatic impairment for clinicians to use the drug more rationally. Methods: A single-center, open-label, parallel-group study was conducted to compare the pharmacokinetic (PK) parameters of contezolid and its metabolite M2 between the patients with moderate hepatic impairment and healthy controls with normal liver function after oral administration of 800mg contezolid tablets. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) of contezolid based on the PK and pharmacodynamic data. Results: Oral treatment with 800mg contezolid tablets was safe and well tolerated in both the patients with moderate hepatic impairment and healthy controls. Moderate hepatic impairment did not result in substantial difference in the area under the concentration-time curve from 0 to 24h (AUC0-24h, 106.79 vs. 97.07hμg/mL) of contezolid even though lower maximum concentration (Cmax, 19.03 vs. 34.49μg/mL) compared with healthy controls. The mean cumulative amount excreted in urine from 0 to 48h (Ae0-48h) and renal clearance (CLR) of contezolid did not show significant difference between the two groups. Moderate hepatic impairment was associated with lower Cmax, slightly lower AUC and Ae0-48h of M2 compared to the healthy controls. fAUC/MIC was the best PK/PD index to predict the clinical efficacy of contezolid. Monte Carlo simulation results indicated that at the proposed fAUC/MIC target value of 2.3, the dosing regimen of oral contezolid 800mg q12h could achieve satisfactory PTA and CFR (both >90%) for the target pathogen (methicillin-resistant S. aureus, MIC ≤4mg/L) in patients with moderate hepatic impairment. Conclusion: Our preliminary data suggest that dose adjustment is not required for contezolid in patients with moderate hepatic impairment. Clinical Trial Registration: https://chinadrugtrials.org.cn, identifier: CTR20171377.

Selective and Continuous Oil Removal from Oil-Water Mixtures Using a Superhydrophobic and Superoleophilic Stainless Steel Mesh Tube.

The development of continuous oil-water separation processes has applications in the treatment of industrial oily wastewater and effective management of oil spills. In this research, the performance of a superhydrophobic-superoleophilic (SHSO) membrane in oil-water separation is investigated through dynamic tests. We investigate the effects of the total flow rate and oil concentration on the separation efficiency using an as-fabricated SHSO mesh tube. To construct the SHSO membrane, a tubular stainless steel mesh is dip-coated into a solution, containing a long-chain alkyl silane (Dynasylan F8261) and functionalized silica nanoparticles (AEROSIL R812). The as-prepared SHSO mesh tube illustrates a water contact angle of 164° and an oil contact angle of zero for hexane. A maximum oil separation efficiency (SE) of 97% is obtained when the inlet oil-water mixture has the lowest flow rate (5 mL/min) with an oil concentration of 10 vol %, while the minimum oil SE (86%) is achieved for the scenario with the highest total flow rate (e.g., 15 mL/min) and the highest oil concentration (e.g., 50 vol %). The water SE of about 100% in the tests indicates that the water separation is not affected by the total flow rate and oil concentration, due to the superhydrophobic state of the fabricated mesh. The clear color of water and oil output streams also reveals the high SE of both phases in dynamic tests. The outlet oil flux increases from 314 to 790 (L/m2·h) by increasing the oil permeate flow rate from 0.5 to 7.5 (mL/min). The linear behavior of the cumulative amounts of collected oil and water with time demonstrates the high separation performance of a single SHSO mesh, implying no pore blocking during dynamic tests. The significant oil SE (97%) of the fabricated SHSO membrane with robust chemical stability shows its promising potential for industrial-scale oil-water separation applications.

Research and Application of Low Frequency and High Amplitude Depressurization Technology in Yi 59 Block

Yi 59 block as the main block of Changchun, With the deepening of water injection development, Unstable water quality, measure, Influence of factors such as operation, increase in cumulative amount, Water injection pressure increased year by year, High pressure under injection problem increasingly significant, 19-year injection-production ratio drops to 1, Seriously restricting block development, Urgent governance. This article from the reservoir physical properties—source control—Start with daily management, the mechanism of reservoir blockage is analyzed, Preliminary demonstration of low frequency high amplitude depressurization injection enhancement technology, indoor evaluation, Field Application and Parameter Optimization, Effective management of under-injection wells, Achieved block smooth water injection, Great application prospect.

Full sexual maturity-cycle exposure to environmentally relevant concentrations of 17β-estradiol decreases reproductive capacity of zebrafish

17β-Estradiol (E2) has been widely detected in natural water and treatment with E2 induces potential endocrine disrupting effects in fish. However, effects on fish fecundity and steroid system after treatment with environmentally relevant concentrations of E2 for the full sexual maturation cycle remain unclear. In this study, zebrafish were treatment with 0, 10 or 100 ng/L E2 from embryo to adult stage, and effects on gonadal development and differentiation, steroid hormone levels, transcription of genes associated with the hypothalamic-pituitary-gonadal-liver (HPG) axis in adults and fertilization rate of offspring were assessed. The results showed that treatment with E2 lead to increased number of feminization in zebrafish. In females, E2 decreased cumulative amount of spawning and inhibited the maturation of oocyte. In males, E2 inhibited the maturation and motility of sperm, as well as decreased the movement speed of sperm. These adverse effects on sperm might be responsible for the reduced fertilization observed in offspring. In addition, treatment with E2 changed the levels of steroid hormones in zebrafish gonad and altered the transcriptional levels of genes associated with HPG axis, which is responsible for the regulation of germ cells maturation and gonadal development in zebrafish. Overall, these results suggested that treatment with environmentally relevant concentrations of E2 for the full sexual maturity cycle resulted in adverse effects on reproduction in zebrafish.

Development and in-vitro evaluation of chitosan and glyceryl monostearate based matrix lipid polymer hybrid nanoparticles (LPHNPs) for oral delivery of itraconazole

Itraconazole (ICZ) is a broad spectrum antifungal drug, but used as second or third line therapy due to its low and erratic oral bioavailability. This work was carried out to prepare and characterize matrix type lipid-polymer hybrid nanoparticles (LPHNPs) for dissolution enhancement of ICZ. LPHNPs were prepared using solvent diffusion/emulsification technique. Matrix LPHNPs were composed of chitosan (polymer), glyceryl monostearate (lipid) and poloxamer 188 (stabilizer). LPHNPs loaded with ICZ (LPHNPs-1, LPHNPs-2, LPHNPs-3 and LPHNPs-4) were developed using varying concentration of chitosan whereas LPHNPs (LPHNPs-5, LPHNPs-6, LPHNPs-7 and LPHNPs-8) were prepared using varying concentrations of poloxamer 188. LPHNPs loaded with ICZ were further evaluated for entrapment efficiency, particle size, polydispersity index (PDI), zeta potential and dissolution profiles at biorelevant pH conditions. The particle size (LPHNPs-1 to LPHNPs-4) was found to be in range of 421–588 nm with PDI values 0.34–0.41. The particles size of LPHNPs-5 to LPHNPs-8 was found to be in range of 489–725 nm with PDI 0.34–0.74. The entrapment efficiency of LPHNPs-1 to LPHNPs-4 was found to be in range of 85.21%–91.34%. The entrapment efficiency of LPHNPs-5 to LPHNPs-8 was found to be in range 78.32%–90.44%. . The scanning electron microscopy of optimized formulations LPHNPs-1 and LPHNPs-5 indicated formation of oval shaped nanoparticles. DSC thermogram of ICZ loaded LPHNPs also depicted the conversion of crystalline form of ICZ into amorphous form demonstrating the internalization and dissolution enhancement of drug in the hybrid matrix. The cumulative drug dissolved at acidic pH 1.2 was found to be 23.3% and 19.8% for LPHNPs-1 and LPHNPs-5 respectively. Similarly at basic pH values 7.4, cumulative amount of drug dissolved was 90.2% and 83.4% for LPHNPs-1 and LPHNPs-5 respectively. Drug dissolution kinetics exhibited fickian diffusion best described by Korse-meyer Peppas model. The results suggested that chitosan and glyceryl monostearate based matrix LPHNPs could be used as promising approach for dissolution enhancement of ICZ which could further increase its bioavailability.

Combination of Dissolving Microneedles with Nanosuspension and Co-Grinding for Transdermal Delivery of Ketoprofen.

Ketoprofen is an anti-inflammatory agent that may cause gastric irritation if administered orally. Dissolving microneedles (DMN) can be a promising strategy to overcome this issue. However, ketoprofen has a low solubility; therefore, it is essential to enhance its solubility using certain methods, namely nanosuspension (NS) and co-grinding (CG). This research aimed to formulate DMN containing ketoprofen-loaded NS and CG. Ketoprofen NS was formulated with poly(vinyl alcohol) (PVA) at concentrations of 0.5%, 1%, and 2%. CG was prepared by grinding ketoprofen with PVA or poly(vinyl pyrrolidone) (PVP) at different drug-polymer ratios. The manufactured ketoprofen-loaded NS and CG were evaluated in terms of their dissolution profile. The most promising formulation from each system was then formulated into microneedles (MNs). The fabricated MNs were assessed in terms of their physical and chemical properties. An in vitro permeation study using Franz diffusion cells was also carried out. The most promising MN-NS and MN-CG formulations were F4-MN-NS (PVA 5%-PVP 10%), F5-MN-NS (PVA 5%-PVP 15%), F8-MN-CG (PVA 5%-PVP 15%), and F11-MN-CG (PVA 7.5%-PVP 15%), respectively. The cumulative amounts of drug permeated after 24 h for F5-MN-NS and F11-MN-CG were 3.88 ± 0.46 µg and 8.73 ± 1.40 µg, respectively. In conclusion, the combination of DMN with nanosuspension or a co-grinding system may be a promising strategy for delivering ketoprofen transdermally.

Preparation and Characterization of a Novel Cassava Starch-Based Phosphorus Releasing Super-Absorbent Polymer, and Optimization of the Performance of Water Absorption and Phosphorus Release.

To prepare a novel cassava starch-based phosphorus releasing super-absorbent polymer (CST-PRP-SAP), the single factor and orthogonal experiment were applied to analyze the effects of different reaction conditions on the absorption and phosphorus release capacities of CST-PRP-SAP samples. The structural and morphological characteristics of the cassava starch (CST), powdered rock phosphate (PRP), cassava starch-based super-absorbent polymer (CST-SAP) and CST-PRP-SAP samples were all compared with various technologies, such as the Fourier transform infrared spectroscopy and X-ray diffraction pattern, etc. The results showed that the CST-PRP-SAP samples had good performances of water retention and phosphorus release which were synthesized, such as the reaction temperature, starch content, P2O5 content, crosslinking agent, initiator, neutralization degree, and acrylamide content, which were 60 °C, 20% w/w, 10% w/w, 0.02% w/w, 0.6% w/w, 70% w/w, and 15% w/w, respectively. The water absorbency of CST-PRP-SAP was almost larger than that of the CST-SAP sample with a P2O5 content of 5.0% and 7.5%, and they all gradually decreased after three consecutive water absorption cycles. The CST-PRP-SAP sample could maintain about 50% of the initial water content after 24 h, even at the temperature of 40 °C. The swelling process of CST-PRP-SAP conformed to the non-Fickian diffusion, which was determined by the diffusion of water molecules and the relaxation process of polymer chain segments. The cumulative phosphorus release amount and release rate of the CST-PRP-SAP samples were increased with the increasing PRP content and the decreasing neutralization degree. After a 216 h immersion, the cumulative phosphorus release amount and release rate of the CST-PRP-SAP samples with different PRP contents were increased by 17.4 and 3.7 times, respectively. The rough surface of the CST-PRP-SAP sample after swelling was beneficial to the performance of water absorption and phosphorus release. The crystallization degree of PRP in the CST-PRP-SAP system was decreased and most of the PRP existed in the form of physical filling, and the available phosphorus content was increased to a certain extent. It was concluded that the CST-PRP-SAP synthesized in this study has excellent properties of continuous water absorption and retention with functions of promotion and the slow-release phosphorus.

Comparative Evaluation of Physiological Response and Drought Tolerance between Cunninghamia unica and C. lanceolata Seedlings under Drought Stress

Cunninghamia plays an important role in China’s southern forest industry in the face of increasingly arid climate; thus it is urgent to identify and screen drought-tolerant varieties. In this study, 2-year-old seedlings of C. unica and C. lanceolata from four provenances were subjected to water-break tests, and their physiological responses to different drought conditions were observed. The results showed that with the aggravation of drought stress, C. unica had more stable changes in relative water content (RWC), water potential (Ψw) and intercellular CO2 concentration (Ci) with more cumulative amounts of proline (PRO) than C. lanceolata, and its H2O2 maintained at a lower level, along with antioxidant enzyme activities decreasing later as compared with C. lanceolata. Moreover, comprehensive evaluation showed that C. unica had a higher drought tolerance than C. lanceolata as a whole, which could have been shaped by maintaining Ψw and opening stomata in its relative drought conditions. This work provides a theoretical basis for understanding the drought tolerance of C. unica and C. lanceolate individuals, so as to accelerate selective breeding in Chinese fir.

Different characteristics of soil CH4 emissions and methanogenic communities in paddy fields under gradually and abruptly elevated CO2 concentrations

Studying methanogenesis in paddy fields under future climate change scenarios is important for carbon sequestration and reduction in agroecosystems. Most studies have investigated the effects of elevated CO2 concentrations (e[CO2]) on CH4 emissions in paddy fields under a constant CO2 concentration ([CO2]). However, the increase in the [CO2] in the atmosphere is a gradual process rather than an abrupt increase, and the [CO2] in the atmosphere has remained high and relatively constant. In this research, we explored the differences in methanogenesis in paddy fields under gradually and abruptly e[CO2] using open-top chambers (OTCs). CH4 flux, soil physicochemical properties, enzyme activities, methane production potential (MPP), and methanogenic (mcrA gene) characteristics were analyzed under CK (ambient [CO2]), C1 (gradually e[CO2] by 200 μmol mol−1), and C2 (abruptly e[CO2] by 200 μmol mol−1) treatments. The results showed that the C1 and C2 treatments significantly promoted the cumulative amount of CH4 emissions (CAC) by 63.3% and 86.5%, respectively, and significantly increased the CAC/yield by 30.8% and 47.3%, respectively, compared with the CK treatment. In addition, the C1 and C2 treatments increased the DOC concentration, enzyme activities (urease, invertase, and catalase), MPP, and mcrA gene abundance in paddy soils. Notably, CAC/yield, shoot biomass, and soil seasonal average urease activity under the C2 treatment were increased by 12.6%, 12.2%, and 3.0%, respectively, compared with those in C1. The methanogenic activity of the C2 treatment was significantly increased by 24.1% and 24.4% during the tillering and grain-filling stages, respectively, and the methanogenic abundance of the C2 treatment was significantly increased by 53.9% and 72.2% during the tillering and elongation stages, respectively, compared with that of C1. Therefore, it is inappropriate to ignore the fact that [CO2] increases gradually and to only examine the effects of high e[CO2] on agroecosystems.

Combined granulation–alkali activation–direct foaming process: A novel route to porous geopolymer granules with enhanced adsorption properties

High-value applications, such as adsorbents, have drawn attention to geopolymers. In several of those applications, having the geopolymer as porous spherical particles is beneficial. This study presents a novel process for fabricating porous metakaolin-based geopolymer granules using a combination of direct foaming, one-part alkali activation, and granulation. In short, the precursor (e.g., metakaolin) and solid activator (e.g., sodium silicate) are loaded in a granulator, in which an aqueous blowing agent (e.g., H2O2) is added while the granulator is running, and the obtained granules are cured at 60 °C. Characterization of the granules for physico-chemical and morphological properties indicated an increase in overall porosity, especially in the µm-scale pores. Also specific surface area (+50%) and nanoscale pore volume (+102%) increased when using more concentrated H2O2 (20 or 30%) compared to nonporous granules. The use of porous granules was also demonstrated in dynamic adsorption experiments for ammonium (NH4+) uptake, which showed up to ∼126% increase in cumulative adsorption amount compared to nonporous granules. The highest NH4+ uptake was obtained with 10% H2O2 solution as the granulation fluid. The results confirmed the feasibility of the method for introducing porosity to geopolymer granules, which enhances the adsorption properties of the granules.

Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice.

The sleep disorder narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic male orexin/tTA; TetO-DTA mice. TAK-925 (1-10mg/kg, s.c.) and ARN-776 (1-10mg/kg, i.p.) were injected 15 min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc ) and activity were recorded by telemetry; recordings for the first 6 h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the second hour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6 h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterised by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the second hour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity, and Tsc , suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HCRTR2 agonists.

Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of Mirogabalin in Healthy Chinese Participants: A Randomized, Double-Blind, Placebo-Controlled Study.

Mirogabalin is a treatment option for patients with neuropathic pain; however, safety, tolerability, and pharmacokinetics (PK) data specifically for Chinese individuals are limited to a single-dose study. We aimed to assess these for both single- and multiple-dose mirogabalin in healthy Chinese participants. In this randomized, double-blind, placebo-controlled, phase I study, 54 healthy Chinese men and women aged 18-45years were randomly allocated to receive single- (5, 10, or 15mg, daily) or multiple-dose (5mg titrated to 15mg, twice-daily, over 22days) oral mirogabalin or placebo. In each of three single-dose groups, 10 participants received mirogabalin and 2 received placebo; in the multiple-dose group, 14 participants received mirogabalin and 4 received placebo. The primary endpoints were PK, safety, and tolerability variables, including treatment-emergent adverse events (TEAEs), laboratory tests, and vital signs. PK data were collected for both single- and multiple-dose cohorts and evaluated by non-compartmental analysis. Single- and multiple-dose mirogabalin was generally well tolerated with no deaths, serious TEAEs, or TEAEs leading to treatment discontinuation. Frequently reported TEAEs included dizziness, nystagmus, increased blood triglycerides, headache, and increased blood uric acid and creatine phosphokinase. Single-dose mirogabalin was rapidly absorbed (median time to maximum plasma concentration, 1.00h) and eliminated (mean terminal elimination half-life, 2.57-3.08h). The exposure was approximately dose-proportional. In the multiple-dose cohort, the trough plasma concentration increased dose-proportionally, and exposure and clearance were comparable to that following a single 15-mg dose. The mean cumulative amount excreted into urine up to 48h post-dose increased in a dose-proportional manner, the mean cumulative percentage excreted into urine was 61.9%-74.3%, and renal clearance remained relatively constant. Consistent with previous phase I studies in other populations, mirogabalin was safe and well tolerated in healthy Chinese participants at single and multiple doses of up to 15mg twice-daily.