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Futibatinib is an excellent fibroblast growth factor receptor 1–4 (FGFR 1–4) inhibitor that exhibits selective anti-tumor activeness against FGFR-deregulated tumors. A new high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technique for the quantitative analysis of futibatinib in beagle dog plasma was developed, and the effect of Yinchenhao decoction (YCHD) on the pharmacokinetics of futibatinib was evaluated. After processing plasma samples with ethyl acetate extraction in the alkaline condition of sodium carbonate, a C18 column (4.6 mm × 150, 5 μm) was used to accomplish the separation of futibatinib and ripretinib (internal standard, ISTD), with the mobile phase consisting of methanol and 0.1% formic acid in water (60:40). The scanning method adopted a multiple reaction monitoring (MRM) mode with positive ion detection through the triple quadrupole mass spectrometer. The ion transitions for futibatinib and IS were m/z 419.20 → 296.15 and m/z 510.36 → 417.00, respectively. Futibatinib displayed excellent linearity in the range of 1–200 ng/mL. Neither inter-day nor intra-day precision exceeded 6.3%. The %RE values for accuracy ranged from −3.1% to 0.9%. The recovery, stability, and matrix effect of futibatinib also complied with the guidelines for the validation of quantitative analysis methods for biological samples in the 2020 edition of the Chinese Pharmacopoeia. In combination with YCHD, the Cmax of futibatinib increased by 40.84% compared to futibatinib dosage alone., and the AUC(0–t) and AUC(0–∞) of futibatinib increased by 78.06% and 82.71%, respectively. The Vd and CL of futibatinib were reduced by 20.05% and 40.85%, respectively. T1/2 was extended from 3.88 h to 5.26 h. The results indicated that YCHD could affect the pharmacokinetics of futibatinib and increase the plasma exposure of futibatinib. If YCHD is administered along with futibatinib, this study gives a first impression how pharmacokinetics and toxicokinetics would change. [ABSTRACT FROM AUTHOR]

Pexidartinib offered a new therapeutic option for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) who were refractory to surgical treatment and had severe morbidity or functional limitations. Meanwhile, the metabolism of pexidartinib was mainly mediated through the oxidation of cytochrome P450 (CYP) 3A and glucuronidation by uridine glucuronosyltransferase (UGT) 1A4 and attention shall be paid to CYP450-based drug-drug interactions during therapeutic dosing. This study aimed to examine the changes in the pharmacokinetics of pexidartinib by silymarin and compound glycyrrhizin on pexidartinib in vivo in rats by high-performance liquid chromatography (HPLC)-UV approach and to detect its expression in CYP3A4 and CYP2C9 using the western blot. The findings of chromatography experiments revealed that silybinin as well as compound glycyrrhizin increased the exposure of pexidartinib in rats and had a significant inhibitory effect on the metabolism of pexidartinib. The results of immunoblotting assays suggested that silybinin as well as compound glycyrrhizin inhibited the protein expression of CYP3A4 and CYP2C9 in rats. Therefore, the combination of pexidartinib with silybinin and compound glycyrrhizin should be monitored to avoid clinical adverse effects. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the effects of various doses of compost amendment on bacterial community compositions and co-occurrence network patterns across the growing season in black soil, Northeast China. Bacterial richness was unaffected by compost addition in seedling and flowering stage, whereas significantly enhanced by high level of compost addition (45,000 kg ha−1) in mature stage. Non-metric multidimensional scaling analysis revealed distinct bacterial communities in response to compost addition across the growing season. At phylum level, copiotrophic groups of bacteria including Bacteroidetes and Firmicutes gradually increased in relative abundance along with compost rate, while oligotrophic groups (Planctomycetes and Verrucomicrobia) showed opposite tendency. Notably, these enrichment or reduction was most pronounced in seedling stage. Abundant genera including Actinomadura, Aminobacter, Cellvibrio, Devosia, Luteimonas, Microbacterium, Nonomuraea, Promicromonospora were positively and consistently correlated with compost rate, whereas Arthrobacter, Flavisolibacter, Janthinobacterium, Kaistobacter negatively correlated. Network analysis indicated that compost amended soils (40.0, 49.0, and 64.0%) harbored more positive links than control (37.6%). In addition, the soil bacterial network connectivity and connectedness generally increased along with the compost rate, while modularity exhibited opposite trend. Overall, our findings show that compost addition modified the bacterial community compositions and network patterns in soybean agroecosystem in Northeast China. [ABSTRACT FROM AUTHOR]

A Rh(I)/Sc(III) co-catalyzed synthesis of highly valuable functionalized 1,4-diketone derivatives in good yields and with an excellent diastereoselectivity. The established method provides a rapid approach to structurally diverse 1,4-diketone scaffold in a very mild and rapid fashion from simple starting materials. Moreover, the protocol could be easily scaled up to gram-scale synthesis. An attempt to develop an asymmetric version of the Rh(I)/guanidine system was also explored, resulting in a moderate enantioselectivity (71% ee). [ABSTRACT FROM AUTHOR]

Summary Plant phenology, the timing of recurrent biological events, shows key and complex response to climate warming, with consequences for ecosystem functions and services. A key challenge for predicting plant phenology under future climates is to determine whether the phenological changes will persist with more intensive and long‐term warming. Here, we conducted a meta‐analysis of 103 experimental warming studies around the globe to investigate the responses of four phenophases – leaf‐out, first flowering, last flowering, and leaf coloring. We showed that warming advanced leaf‐out and flowering but delayed leaf coloring across herbaceous and woody plants. As the magnitude of warming increased, the response of most plant phenophases gradually leveled off for herbaceous plants, while phenology responded in proportion to warming in woody plants. We also found that the experimental effects of warming on plant phenology diminished over time across all phenophases. Specifically, the rate of changes in first flowering for herbaceous species, as well as leaf‐out and leaf coloring for woody species, decreased as the experimental duration extended. Together, these results suggest that the real‐world impact of global warming on plant phenology will diminish over time as temperatures continue to increase. [ABSTRACT FROM AUTHOR]

Objective: To investigate the levels and influencing factors of phthalate internal exposure in pregnant women (gestation age ≤ 16 weeks)., Methods: During April to June in 2013, 1 020 pregnant women (gestation age ≤ 16 weeks) who had established the maternal care manual were recruited in maternal and child health hospital of Siming District, Xiamen city. Participators were asked to complete a questionnaire to obtain information on socio-demographic characteristics, lifestyle behaviors, and antenatal examination and to provide a urine sample. Finally, 998 pregnant women who provided a urine sample and completed the questionnaire were enrolled. Adopting systematic sampling method, 100 ones were selected randomly among 998 pregnant women. High performance liquid chromatography-electrospray ionization-tandern mass was used to determine the concentration of five phthalate monoesters in each urine, including mono-n-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-ethylhexyl phthalate (MEHP). Based on the measurements and questionnaire data, multivariate logistic regression was used to analyze the association between the phthalate monoester levels and potential influential factors., Results: The detection rates of MMP, MEP, MBP, MBzP and MEHP in 100 pregnant urine samples were 94%, 93%, 87%, 83%, 99%, respectively. And the urinary median uncorrected concentrations of MMP, MEP, MBP, MBzP and MEHP in 100 urine samples were 20.56, 17.62, 10.15, 2.03, and 5.12 ng/ml, respectively. Specific gravity-corrected concentration were 20.81, 20.36, 12.88, 2.58, 5.00 ng/ml, respectively. The results of multivariate logistic regression analysis indicated that: education degree was negatively associated with urinary concentration of MMP, MEP, MBP, MBzP and MEHP, OR (95% CI) were 0.495 (0.253-0.966), 0.380 (0.191-0.755), 0.379 (0.186-0.774), 0.401 (0.196-0.819), 0.373(0.183-0.762), respectively. Participants who had hair permed and dyed during pregnancy had higher urinary level of MBP and MBzP, OR (95% CI) were 12.867 (1.240-133.525), 15.982 (1.367-186.911), respectively; Participants who use cosmetics during pregnancy had higher urinary level of MEP and MBP, OR (95% CI) were 2.977 (1.012-8.757), 4.440 (1.485-13.272), respectively; plastic bottled water consumption was positively associated with urinary concentrations of MEP and MEHP, OR (95% CI) were 3.780 (1.417-10.083), 2.699 (1.039-7.010), respectively; annual household income was negatively associated with urinary concentration of MMP, OR (95% CI) was 0.597 (0.372-0.959); individuals who took medications during pregnancy had higher urinary level of MEHP than non-takers, OR (95% CI) was 4.853 (1.084-21.732)., Conclusion: Pregnant women whose gestation age was less than 16 weeks are generally exposed to phthalate. Phthalate internal exposure levels are significantly associated with most measured factors and the influencing factors with different phthalates internal exposure levels are different.

The asymmetric unit of the title compound, [Mn(C(8)H(7)N(3))(3)](2)[PMo(12)O(40)]·6H(2)O, consists of a complex [Mn(C(8)H(7)N(3))(3)](2+) cation, half of a mixed-valent Mo(V,VI) α-Keggin-type [PMo(12)O(40)](4-) heteropolyanion, and three uncoordinated water mol-ecules. The Mn(2+) cation is surrounded by six N atoms from three chelating 3-(2-pyrid-yl)-1H-pyrazole ligands in a distorted octa-hedral coordination. In the heteropolyanion, two O atoms of the central PO(4) group ( symmetry) are equally disordered about an inversion centre. N-H⋯O and O-H⋯O hydrogen bonding between the cations, anions and the uncoordinated water mol-ecules leads to a consolidation of the structure.