Ru Regulated Electronic Structure of Pdx Cuy Nanosheets for Efficient Hydrogen Evolution Reaction in Wide pH Range.

The development of highly effective catalysts for hydrogen evolution reaction (HER) in a wide pH range is crucial for the sustainable utilization of green energy utilization, while the slow kinetic reaction rate severely hinders the progress of HER. Herein, the reaction kinetic issue is solved by adjusting the electronic structure of the Ru/Pdx Cuy catalysts. The champion catalyst displays a remarkable performance for HER with the ultralow overpotential (27, 28, and 97 mV) in 1.0 m KOH, 0.5 m H2 SO4 , and 1.0 m PBS at 10 mA cm-2 and high the mass activity (3036 A g-1 ), respectively, superior to those of commercial Pt/C benchmarks and most of reported electrocatalysts, mainly due to its low reaction activation energy. Density functional theory (DFT) calculations indicate that Ru doping contributes an electron-deficient 3d band, which promotes water adsorption. Additionally, this also leads to an upward shift of the d-band center of Pd and a downward shift of the d-band center of Cu, further optimizing the adsorption/dissociation of H2 O and H* . Results from this work may provide an insight into the design and synthesis of high-performance pH-universal HER electrocatalysts.

Hemin/G-quadruplex and AuNPs-MoS2 based novel dual signal amplification strategy for ultrasensitively sandwich-type electrochemical thrombin aptasensor.

In this work, a novel sandwich-type electrochemical aptasensor based on the dual signal amplification strategy of hemin/G-quadruplex and AuNPs-MoS2 was designed and constructed, which realized the highly sensitive and specific detection of thrombin (TB). In this aptasensor, the 15-mer TB-binding aptamer (TBA-1) modified with thiol group was immobilized on the surface of AuNPs modified glassy carbon electrode (AuNPs/GCE) as capturing elements. Another thiol-modified 29-mer TB-binding aptamer (TBA-2) sequence containing G-quadruplex structure for hemin immobilization was designed. The formed hemin/G-quadruplex/TBA-2 sequence was further combined to the AuNPs decorated flower-like molybdenum disulfide (AuNPs-MoS2) composite surface via Au-S bonds, acting the role of reporter probe. In presence of the target TB, the sandwich-type electrochemical aptamer detection system could be formed properly. With the assistance of the dual signal amplification of AuNPs-MoS2 and hemin/G-quadruplex toward H2O2 reduction, the sandwich-type electrochemical aptasensor was successfully constructed for sensitive detection of TB. The results demonstrate that the fabricated aptasensor displays a wide linear range of 1.0 × 10-6 âˆ¼ 10.0 nM with a low detection limit of 0.34 fM. This proposed aptasensor shows potential application in the detection of TB content in real biological samples with high sensitivity, selectivity, and reliability.

Confined Ni nanoparticles in N-doped carbon nanotubes for excellent pH-universal industrial-level electrocatalytic CO2 reduction and Zn-CO2 battery.

Electrocatalytic reduction of CO2 (ECR) offers a promising approach to curbed carbon emissions and complete carbon cycles. However, the inevitable creation of carbonates and limited CO2 utilization efficiency in neutral or alkaline electrolytes result in low energy efficiency, carbon losses and its widespread commercial utilization. The advancement of CO2 reduction under acidic conditions offers a promising approach for their commercial utilization, but the inhibition of hydrogen evolution reaction and the corrosion of catalysts are still challenging. Herein, Ni nanoparticles (NPs) wrapped in N-doped carbon nanotubes (NixNC-a) are successfully prepared by a facile mixed-heating and freeze-drying method. Ni100NC-a achieves a high Faraday efficiency (FE) of near 100 % for CO under pH-universal conditions, coupled with a promising current density of CO (>100 mA cm-2). Especially in acidic conditions, Ni100NC-a exhibits an exceptional ECR performance with the high FECO of 97.4 % at -1.44 V and the turnover frequency (TOF) of 11 k h-1 at -1.74 V with a current density of 288.24 mA cm-2. This excellent performance is attributed to the synergistic effect of Ni NPs and N-doped carbon shells, which protects Ni NPs from etching, promotes CO2 adsorption and regulates local pH. Moreover, Ni100NC-a could drive the reversible Zn-CO2 battery with a high power-density of 4.68 mW cm-2 and a superior stability (98 h). This study presents a promising candidate for efficient pH-universal CO2 electroreduction and Zn-CO2 battery.

Examining the Shift in the Decomposition Channel Structure of the Soil Decomposer Food Web: A Methods Comparison.

Selecting the appropriate indicators and measuring time point numbers is important for accurately examining the shift in soil gross decomposition channel structure. Through a selected case study on a natural forest vs. rainfed arable system over a two-month-long experiment, the utility of three commonly employed indicators (fungi to bacteria ratio (F:B), fungivore to bacterivore ratio (FF:BF), and glucosamine to muramic acid ratio (GlcN:MurN)) were compared to reflect the shift in soil gross decomposition channel structure. The requirement of measuring the time point numbers for the three indicators was also assessed, and we suggest a potential methodology. Our results revealed that the GlcN:MurN ratio was more reliable for assessing the shifts in gross decomposition channel structure for long-term land use changes, while it was less sensitive to short-term drought compared with the other two indicators. The F:B ratio was more applicable than the FF:BF ratio for reflecting both long- and short-term changes. Furthermore, the reliability of the GlcN:MurN ratio was the least dependent on measuring time point numbers. We suggest the use of multiple indicators and the adoption of multiple measuring time points for the overall methodology.

Three-dimensional MoS2-graphene aerogel nanocomposites for electrochemical sensing of quercetin.

A facile and novel electrochemical sensing platform is reported for quercetin determination with MoS2 nanoflowers-3D graphene aerogel (3D MoS2-GA) nanocomposite as signal amplified material. The 3D MoS2-GA nanocomposite was synthesized through a two-step hydrothermal method, in which MoS2 nanoflowers were prepared in advance. Characterizations of 3D MoS2-GA were performed by scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The 3D MoS2-GA-modified glassy carbon electrode (3D MoS2-GA/GCE) was used to investigate the electrochemical behaviors of quercetin with electrochemical parameters calculated, reaction mechanism discussed, and experimental conditions optimized. Notably, the redox peak current densities of quercetin on 3D MoS2-GA/GCE raised 5.14 and 6.40 times compared with those on a bare GCE. Furthermore, a novel electroanalytical approach was proposed for the sensitive determination of quercetin within the concentration range 0.01 ~ 5.0 µmol/L, accompanied by a low detection limit of 0.0026 µmol/L (at a working potential of 0.38 V vs. Ag/AgCl). The recovery for practical sample analysis ranges from 97.0 to 105%, and the relative standard deviation is less than 4.2%. This established method shows reliable performance in determination of quercetin in tablets and urine samples.

Large-scale defect-rich iron/nitrogen co-doped graphene-based materials as the excellent bifunctional electrocatalyst for liquid and flexible all-solid-state zinc-air batteries.

Defect-engineering in transition-metal-doped carbon-based catalyst plays an essential role for improving the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) performance. Herein, we report a ball-milling induced defect assisted with ZnCl2 strategy for fabricating defect-rich iron/nitrogen co-doped graphene-based materials (Fe-N-G). The substantial mechanical shear forces and the constant corrosion to the carbon matrix by ZnCl2 lead to the creation of abundant defects in graphene-based materials, which facilitates doping for heteroatoms. The defect-rich Fe-N-G catalyst with abundant Fe-Nx active sites displays excellent ORR performance. For OER, the over potential for Fe-N-G outperforms that of RuO2 in 1 M KOH at 10 mA cm-2. The Density Functional Theory calculations unravel that the impressive OER performance is attributable to the introduction of abundant defects. Additionally, the liquid and all-solid-state zinc-air batteries equipped with the prepared material as the air cathode demonstrate high power density, high specific capacity, and long charge-discharge stability. This work offers a practical method for manufacturing high-performance electrocatalysts for environmental and energy-related fields.

Prophage Gene Rv2650c Enhances Intracellular Survival of Mycobacterium smegmatis.

BACKGROUND: Induced by the pathogen Mycobacterium tuberculosis, tuberculosis remains one of the most dangerous infectious diseases in the world. As a special virus, prophage is domesticated by its host and are major contributors to virulence factors for bacterial pathogenicity. The function of prophages and their genes in M. tuberculosis is still unknown. METHODS: Rv2650c is a prophage gene in M. tuberculosis genome. We constructed recombinant Mycobacterium smegmatis (M. smegmatis) to observe bacteria morphology and analyze the resistance to various adverse environments. Recombinant and control strains were used to infect macrophages, respectively. Furthermore, we performed ELISA experiments of infected macrophages. RESULTS: Rv2650c affected the spread of colonies of M. smegmatis and enhanced the resistance of M. smegmatis to macrophages and various stress agents such as acid, oxidative stress, and surfactant. ELISA experiments revealed that the Rv2650c can inhibit the expression of inflammatory factors TNF-α, IL-10, IL-1ß, and IL-6. CONCLUSION: This study demonstrates that the prophage gene Rv2650c can inhibit the spread of colonies and the expression of inflammatory factors and promote intracellular survival of M. smegmatis. These results build the foundation for the discovery of virulence factors of M. tuberculosis, and provide novel insights into the function of the prophage in Mycobacterium.

Bacteriophages in water pollution control: Advantages and limitations.

Wastewater is a breeding ground for many pathogens, which may pose a threat to human health through various water transmission pathways. Therefore, a simple and effective method is urgently required to monitor and treat wastewater. As bacterial viruses, bacteriophages (phages) are the most widely distributed and abundant organisms in the biosphere. Owing to their capacity to specifically infect bacterial hosts, they have recently been used as novel tools in water pollution control. The purpose of this review is to summarize and evaluate the roles of phages in monitoring pathogens, tracking pollution sources, treating pathogenic bacteria, infecting bloom-forming cyanobacteria, and controlling bulking sludge and biofilm pollution in wastewater treatment systems. We also discuss the limitations of phage usage in water pollution control, including phage-mediated horizontal gene transfer, the evolution of bacterial resistance, and phage concentration decrease. This review provides an integrated outlook on the use of phages in water pollution control.

Chloroplast genome sequence of a yellow colored rice (Oryza sativa L.): insight into the genome structure and phylogeny.

Colored rice is gaining popularity due to its use in creative agriculture and the value of healthy consumption. However, the quality and yield characteristics of most rice varieties still need to be improved. Revealing the genetic background of colored rice is of great significance to promote crop improvement. Here, the completed chloroplast (cp) genome sequence of yellow colored Oryza sativa voucher HSAGSDYD1802 was sequenced and reported. It was a 134,502 bp circular DNA with a typical quadripartite structure, consisting of two reverse repeat regions (IRa and IRb, 20,804 bp) separated by a large single-copy region (LSC, 80,547 bp) and a small single-copy region (SSC, 12,347 bp). The total GC content was 39%. The cp genome encoded 146 genes, containing 100 protein-coding genes, 8 rRNAs, and 38 tRNA genes. Phylogenetic analysis indicated that O. sativa voucher HSAGSDYD1802 was closely related to O. sativa L. TN1, RP Bio-226 and IR8. This study enriches the genetic information of colored rice and is helpful for future molecular breeding.

Highly Exposed Active Sites of Fe/N Co-doped Defect-rich Graphene as an Efficient Electrocatalyst for Oxygen Reduction Reaction.

A defect-rich interconnected hierarchical three-dimensional Fe and N co-doped graphene has been prepared by a facile synthesis with poly (2,5-benzimidazole) (ABPBI) as nitrogen and carbon sources and CaCO3 as the template. ABPBI possesses abundant nitrogen, and pyrolysis of ABPBI is helpful to form graphene structure. CaCO3 and its decomposition products CO2 can promote the formation of interconnected hierarchical porous three-dimensional graphene, which possesses more defects and exposed active sites. Benefiting from the defective catalysis mechanism, rich defect catalysts are applied as electrode materials to enhance the catalytic performance for oxygen reduction reaction (ORR). Electrochemically, the half-wave potential (E1/2 ) of Fe-3D-NG#800 is 0.84 V (vs. RHE), and the accelerated durability tests shows the E1/2 of Fe-3D-NG#800 shifted by a 21 mV drop after cyclic voltammetry scanning for 5000 cycles. Therefore, Fe-3D-NG#800 has excellent activity and durability than 20 wt % Pt/C.

Lack of effect of Imrecoxib, an innovative and moderate COX-2 inhibitor, on pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers.

Imrecoxib is a registered treatment for osteoarthritis pain symptoms in China. This study aims to assess the effect of imrecoxib on the pharmacodynamics and pharmacokinetics of warfarin. 12 healthy male volunteers with CYP2C9*3 AA and VKORC1 AA genotypes took a 5 mg dose of warfarin both alone and concomitantly with steady-state imrecoxib. Both warfarin alone and concomitantly with imrecoxib have safey and good tolerance across the trial. Following warfarin and imrecoxib co-administration, neither Cmax, AUC0-t and t1/2 of warfarin enantiomers nor AUC of international normalized ratio (INR) were markedly different from those of warfarin alone. The geometric mean ratios (GMRs) (warfarin + imrecoxib: warfarin alone) of INR(AUC) was 1 (0.99, 1.01). The GMRs of warfarin AUC0-∞ (90% confidence interval, CIs) for warfarin + imrecoxib: warfarin alone were 1.12 (1.08, 1.16) for R-warfarin and 1.13 (1.07, 1.18) for S- warfarin. The 90% CIs of the GMRs of AUC0-∞, Cmax and INR (AUC) were all within a 0.8-1.25 interval. The combination of warfarin and imrecoxib did not impact the pharmacodynamics and pharmacokinetics of single-dose warfarin; therefore, when treating a patient with imrecoxib and warfarin, it is not required to adjust the dosage of warfarin.

A time- and cost-effective synthesis of CHA zeolite with small size using ultrasonic-assisted method.

In this paper, the ultrasonic-assisted method has been used to the rapid hydrothermal synthesis of CHA zeolite in the absence of expensive organic template. The influence of different sonicated time on the crystallinity and micromorphology of CHA-type crystals has been studied in detail. The bath-type ultrasound processor produces acoustic waves at the frequency of 20 kHz and the power of ultrasound wave is 150 W. The synthesized products have been characterized by XRD, SEM, EDX, TG and N2 adsorption analyses. Due to the acceleration on homogeneous nucleation caused by acoustic cavitation cracks during the ultrasonic vibrative process, the crystallization time can be shorten from 48 h to 10 h and the crystal size can be reduced from about 20 µm to 5 µm. The SEM observations of samples with different ultrasonic treatment time distinctly revealed the morphology evolution of the walnut-like CHA zeolites. From EDX, TG and N2 adsorption comparisons, it is clear that untreated sample and ultrasonic sample both have similar element distribution, thermal stability, and pore size distribution. The research work in this paper has demonstrated the ultrasonic treatment can significantly improve crystallinity degree, reduce crystallization time and crystal size of CHA zeolite.

Spinel MnCo2 O4 Nanoparticles Supported on Three-Dimensional Graphene with Enhanced Mass Transfer as an Efficient Electrocatalyst for the Oxygen Reduction Reaction.

The rational design of highly efficient and durable oxygen reduction reaction (ORR) catalysts is critical for the commercial application of fuel cells. Herein, three-dimensional graphene (3D-G) is synthesized by the template method, which used coal tar pitch as the carbon source and nano MgO as the template. Then, spinel MnCo2 O4 is in situ supported on the 3D-G by a facile hydrothermal method, giving MnCo2 O4 /3D-G. The resultant MnCo2 O4 /3D-G retains the multilayered mesoporous graphene structure where MnCo2 O4 nanoparticles are deposited on the inner walls of pores in the 3D-G. The catalyst MnCo2 O4 /3D-G shows high electrocatalytic activity with a half-wave potential of 0.81 V versus reversible hydrogen electrode, which is clearly superior to those of MnCo2 O4 /reduced graphene oxide (0.78 V), MnCo2 O4 /carbon nanotubes (0.74 V), MnCo2 O4 /C (0.72 V), and 20 wt % Pt/C (0.80 V). The electron transfer number of MnCo2 O4 /3D-G indicates a four-electron process of ORR. The durability test demonstrates that the MnCo2 O4 /3D-G catalyst has a much better durability than 20 wt % Pt/C. Our work makes an inspiring strategy to prepare high-performance electrocatalysts for the development of fuel cells.

Long-term effects of nitrogen fertilization on aggregation and localization of carbon, nitrogen and microbial activities in soil.

Long-term nitrogen (N) fertilization affects soil aggregation and localizations of soil organic carbon (SOC), N and microbial parameters within aggregates. The mechanisms of these N effects are poorly understood. We studied these processes in a loamy soil from a 23-year repeated N addition field experiment under a rice-barley rotation. Nitrogen fertilization increased plant productivity and the portion of large macroaggregates (>2mm). However, SOC contents in macro- and micro-aggregates remained constant despite an N-induced increase of 27% in root C input into soil. Therefore, N fertilization accelerated SOC turnover. Nitrogen addition increased total N (TN) content in bulk soil and two macroaggregates (>2, and 1-2mm), but not in microaggregates (<0.25mm). Also, N fertilization increased the phospholipid fatty acids (PLFAs) contents of fungi in the large macroaggregates, but not in the microaggregates. In contrast, the effect of N addition on contents of bacterial and total microbial PLFAs was not apparent. Nitrogen fertilization increased N-acetyl-ß-D-glucosaminidase (NAG) activities in the two larger macroaggregate size classes (>2, and 1-2mm), but not in the aggregates (<1mm). In both control and N fertilization, the large macroaggregates localized more TN, microbial PLFAs, and NAG activities than the microaggregates. In conclusion, long-term N fertilization not only directly promotes soil N resource but also indirectly improves soil structure by forming large macroaggregates, accelerates SOC turnover, and shiftes localization of microorganisms to the macroaggregates.

A synthetic analysis of greenhouse gas emissions from manure amended agricultural soils in China.

Application of manure has been recommended as an effective strategy to to mitigate climate change. However, the magnitude of greenhouse gases emission derived by application of manure to agricultural soils across environmental conditions still remains unclear. Here, we synthesized data from 379 observations in China and quantified the responses of soil nitrous oxide (N2O), carbon dioxide (CO2) and methane (CH4) emissions to manure (Org-M) in comparison to chemical fertilizers (Min-F) or non-fertilizers (Non-F). The results showed that N2O, CO2 and CH4 emissions were significantly affected by Org-M compared to Min-F (percentage change: -3, +15 and +60%, P < 0.05) and Non-F (percentage change: +289, +84 and +83%, P < 0.05), respectively. However, at the same amount of total N input, Org-M decreased soil N2O emission by 13% and CH4 emission by 12%, and increased soil CO2 emission by 26% relative to Min-F in upland soils. For paddy soils, N2O, CO2 and CH4 emissions differed by -3%, -36% and +84% between Org-M and Min-F (i.e., Org-M minus Min-F). Thus, practices such as application of manure instead of chemical fertilizer and decreasing nitrogen input rate need to be highly considered and optimized under different soils and climate conditions to mitigate GHGs emission in China.

Tolerability and Pharmacokinetics of Hydronidone, an Antifibrotic Agent for Hepatic Fibrosis, after Single and Multiple Doses in Healthy Subjects: an Open-Label, Randomized, Dose-Escalating, First-in-Human Study.

BACKGROUND AND OBJECTIVES: Hydronidone is a novel pyridine derivative with therapeutic potential for hepatic fibrosis. The aim of this study was to investigate the safety, tolerability, and pharmacokinetics of hydronidone in healthy subjects. Effects of sex and food on hydronidone pharmacokinetics were also evaluated. METHODS: A randomized, dose-escalating, first-in-human study was conducted in 88 subjects. Five cohorts of 34 subjects received a single dose of hydronidone capsules at 15-120 mg, and two cohorts of 12 subjects received 90 and 120 mg of hydronidone thrice daily for 7 days, and six subjects received 60 mg of hydronidone thrice daily for 28 days to assess the safety and tolerability. In 36 subjects, hydronidone pharmacokinetics were investigated following oral administration of single (30, 60, and 120 mg) and multiple (60 mg, thrice daily) doses of hydronidone. RESULTS: Plasma concentrations of hydronidone and area under the concentration-time curve were found to be proportional to dose. Hydronidone was rapidly absorbed [median time to maximum plasma concentration (t max) = 0.33-0.63 h] and cleared [terminal elimination half-life (t 1/2) = 1.72-3.10 h]. Pharmacokinetic parameters after multiple doses were similar to those after single dose. Food had a significant affect (P < 0.01) on the extent and rate of absorption. No significant sex differences were noted for pharmacokinetic variables. CONCLUSION: Hydronidone was well tolerated and rapidly absorbed, and concomitant intake of food reduced rate and extent (about 20 %) of absorption in healthy volunteers. There was no accumulation following multiple doses of hydronidone. These results support a 60 mg thrice-daily regimen for management of hepatic fibrosis and further development of hydronidone (registered at ClinicalTrials.gov as ChiCTR-ONC-12002899).

Community diversity, structure and carbon footprint of nematode food web following reforestation on degraded Karst soil.

We examined community diversity, structure and carbon footprint of nematode food web along a chronosequence of T. Sinensis reforestation on degraded Karst. In general, after the reforestation: a serious of diversity parameters and community indices (Shannon-Weinier index (H'), structure index (SI), etc.) were elevated; biomass ratio of fungivores to bacterivores (FFC/BFC), and fungi to bacteria (F/B) were increased, and nematode channel ratio (NCR) were decreased; carbon footprints of all nematode trophic groups, and biomass of bacteria and fungi were increased. Our results indicate that the Karst aboveground vegetation restoration was accompanied with belowground nematode food web development: increasing community complexity, function and fungal dominance in decomposition pathway, and the driving forces included the bottom-up effect (resource control), connectedness of functional groups, as well as soil environments.

Effects of enhancing soil organic carbon sequestration in the topsoil by fertilization on crop productivity and stability: Evidence from long-term experiments with wheat-maize cropping systems in China.

Although organic carbon sequestration in agricultural soils has been recommended as a 'win-win strategy' for mitigating climate change and ensuring food security, great uncertainty still remains in identifying the relationships between soil organic carbon (SOC) sequestration and crop productivity. Using data from 17 long-term experiments in China we determined the effects of fertilization strategies on SOC stocks at 0-20cm depth in the North, North East, North West and South. The impacts of changes in topsoil SOC stocks on the yield and yield stability of winter wheat (Triticum aestivum L.) and maize (Zea mays L.) were determined. Results showed that application of inorganic fertilizers (NPK) plus animal manure over 20-30years significantly increased SOC stocks to 20-cm depth by 32-87% whilst NPK plus wheat/maize straw application increased it by 26-38% compared to controls. The efficiency of SOC sequestration differed between regions with 7.4-13.1% of annual C input into the topsoil being retained as SOC over the study periods. In the northern regions, application of manure had little additional effect on yield compared to NPK over a wide range of topsoil SOC stocks (18->50MgCha(-1)). In the South, average yield from manure applied treatments was 2.5 times greater than that from NPK treatments. Moreover, the yield with NPK plus manure increased until SOC stocks (20-cm depth) increased to ~35MgCha(-1). In the northern regions, yield stability was not increased by application of NPK plus manure compared to NPK, whereas in the South there was a significant improvement. We conclude that manure application and straw incorporation could potentially lead to SOC sequestration in topsoil in China, but beneficial effects of this increase in SOC stocks to 20-cm depth on crop yield and yield stability may only be achieved in the South.

Tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects: an open-label, randomized, single-center study.

The tolerability and pharmacokinetics of disodium folinate may vary with different races, and these variations might result in different outcomes. This study assessed the tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects, with gender factor also taken into account. Subjects were randomized to receive a single dose of disodium folinate at 20, 200, or 300 mg/m(2) administered intravenously over a time period of 10 min. Sequential blood samples were collected at regular intervals over 24 h after dosing and were analyzed using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters, including C max, AUC0-t, t 1/2, V d, and CL, were calculated using non-compartmental models. Tolerability was assessed by collecting adverse events (AEs) and monitoring vital signs, physical examinations, laboratory tests, and electrocardiograms. Following a single intravenous administration of disodium folinate 20, 200, and 300 mg/m(2), the mean (standard deviation) pharmacokinetic parameters were as follows: C max = 5.18 (0.58), 47.80 (10.10), and 69.93 (9.72) µg/mL; AUC0-t = 25.85 (3.36), 194.53 (30.18), and 355.26 (35.31) µg h/mL; AUC0-∞ = 30.24 (6.19), 215.43 (27.34), and 417.88 (54.81) µg h/mL; t 1/2 = 8.77 (2.57), 7.64 (1.81), and 9.08 (1.64) h; CL = 1.12 (0.18), 1.55(0.25), and 0.78 (0.09) L/h; V d = 13.75 (2.61), 17.38 (6.44), and 10.05 (1.49) L, respectively. The mean C max, AUC0-t, and AUC0-∞ increased in a dose-proportional manner. No significant differences in pharmacokinetic parameters were noted by gender. The most common AEs reported were mild redness at the injection site and neurological symptoms (headache, dizziness, and fatigue).

Safety, tolerability, pharmacokinetics, and pharmacodynamics of recombinant human parathyroid hormone (1-34) in healthy Chinese subjects.

BACKGROUND: The recombinant human parathyroid hormone (1-34) (rhPTH[1-34]) teriparatide is the first anabolic agent approved by the US Food and Drug Administration for the treatment of osteoporosis in men and women. This study was conducted to provide support for marketing authorization of an agent biosimilar to teriparatide in China. OBJECTIVE: The main aim of the present study was to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic parameters of rhPTH(1-34) after single and multiple subcutaneous doses in healthy Chinese subjects. METHODS: Two open-label, randomized, single-center, dose-escalation studies were performed. In study 1, subjects were randomized to receive a single dose of rhPTH(1-34) (10, 20, 30, 40, 50, or 60 µg) or a multiple dose of rhPTH(1-34) (10 and 20 µg once daily for 7 consecutive days) to determine the safety profile and tolerability, as reflected by the incidence, intensity, and seriousness of the observed adverse events. In study 2, a single dose of rhPTH(1-34) (10, 20, or 40 µg) and a multiple dose of rhPTH(1-34) (20 µg) were administrated subcutaneously to investigate the pharmacokinetic and pharmacodynamic parameters. RESULTS: Forty-two subjects completed study 1, and 30 subjects completed study 2. rhPTH(1-34) was well tolerated during the investigated single (10-60 µg) and multiple (10-20 µg once daily for 7 consecutive days) dose ranges. The most generally reported adverse events were erythema at the injection site and gastrointestinal reactions. After single and multiple subcutaneous administration of rhPTH(1-34), the drug was rapidly absorbed, with a Tmax of 20 to 30 minutes, and rapidly cleared from the plasma, with a t½ of 47.2 to 60.6 minutes. The mean Cmax, AUC0-t, and AUC0-∞ increased in proportion to the doses, whereas the t½, total clearance, and Tmax values were independent of the administered dose. No significant differences in pharmacokinetic parameters were noted by sex except for Tmax in the 10-µg and 20-µg single-dose groups. Compared with the baseline levels, no significant changes or dose-related significant effects were observed in serum calcium and phosphate levels. CONCLUSIONS: All rhPTH(1-34) doses appeared to be well tolerated in the population studied. Linear pharmacokinetic characteristics were displayed in the dose range studied. Chinese ClinicalTrials.gov identifier: ChiCTR-ONC-12002874.