GPER1 contributes to T3-induced osteogenesis by mediating glycolysis in osteoblast precursors.

Triiodothyronine (T3) is critical to osteogenesis, which is the key factor in bone growth. Our transcriptomic and metabolomic analysis results indicated that T3 leads to enhanced expression of G protein-coupled estrogen receptor 1 (GPER1) as well as increases in glycolysis metabolite levels. Accordingly, our study aimed to explore the role of GPER1-mediated glycolysis in T3-regulated osteogenesis. The MC3T3-E1 cell line was used as an osteoblast precursor model. After treatment with T3, a GPER1-specific antagonist (G15) and inhibitor of glycolysis (3PO) were used to explore the roles of GPER1 and glycolysis in T3-regulated osteogenesis, as measured by ALP activity, Alizarin red staining intensity and osteogenic molecule expression. Our results showed that T3 promoted osteogenesis-related activity, which was reversed by treatment with G15. In addition, T3 enhanced the glycolytic potential and production of lactic acid (LD) in MC3T3-E1 cells, and treatment with G15 restored the aforementioned effects of T3. Ultimately, the pharmacological inhibition of glycolysis with 3PO blocked the ability of T3 to enhance osteogenic activities. In conclusion, GPER1 mediates glycolysis in osteoblast precursors, which is critical for T3-promoted osteogenesis.

White-Light Emission and Circularly Polarized Luminescence from a Chiral Copper(I) Coordination Polymer through Symmetry-Breaking Crystallization.

Achieving white-light emission, especially white circularly polarized luminescence (CPL) from a single-phase material is challenging. Herein, a pair of chiral CuI coordination polymers (1-M and 1-P) have been prepared by the asymmetrical assembly of achiral ligands and Cu2 I2 clusters. The compounds display dual emission bands and can be used as single-phase white-light phosphors, achieving a "warm"-white-light-emitting diode with an ultra-high color rendering index (CRI) of 93.4 and an appropriate correlated color temperature (CCT) of 3632 K. Meanwhile, corresponding CPL signals with maximum dissymmetry factor |glum |=8×10-3 have been observed. Hence, intrinsic white-light emission and CPL have been realized simultaneously in coordination polymers for the first time. This work gains insight into the nature of chiral assembly from achiral units and offers a prospect for the development of single-phase white-CPL materials.

1,3,4-thiadiazole: a privileged scaffold for drug design and development.

1,3,4-thiadiazole is a five-membered aromatic heterocycle containing two nitrogen atoms and one sulfur atom. As a privileged scaffold, it has its unique chemical properties and biological characteristics. In the design of drugs, they are widely and flexibly applied by medicinal chemists, and many candidates with therapeutic prospects have been developed. In this review, we focus on 1,3,4-thiadiazole derivatives and their various biological activities reported in the past five years (from 2015 to early 2020), such as anticancer, antibacterial, antifungal, anti-tuberculosis, anti-inflammatory, antivirus, anti-leishmania and other functions. It is believed that this review can provide some new ideas for seeking rational design to develop 1,3,4-thiadiazole based medicinal agents with better activity and lower toxicity.

Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis.

In order to discover and develop drug-like anti-inflammatory agents against arthritis, based on "Hit" we found earlier and to overcome drawbacks of toxicity, twelve series of total 89 novel pyrimidine, pyrazolo[4,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives were designed, synthesized and screened for their anti-inflammatory activity against NO and toxicity for normal liver cells (LO2). Relationships of balance toxicity and activity have been summarized through multi-steps, and title compounds 22o, 22l were found to show lower toxicity (against LO2: IC50 = 2934, 2301 µM, respectively) and potent effect against NO release (IR = 98.3, 97.67%, at 10 µM, respectively). Furthermore, compound 22o showed potent iNOS inhibitory activity with value of IC50 is 0.96 µM and could interfere stability and formation of the active dimeric iNOS. It's anti-inflammatory activity in vivo was assessed by AIA rat model. Furthermore, the results of metabolic stability, CYP, PK study in vivo, acute toxicity study and subacute toxicity assessment indicated this compound had good drug-like properties for treatment.

Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety.

Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 < 1 µM), which was significantly superior to the staurosporine (IC50 = 6.41 µM). In addition, clear structure-activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase.

Soil bacterial and fungal community successions under the stress of chlorpyrifos application and molecular characterization of chlorpyrifos-degrading isolates using ERIC-PCR.

Chlorpyrifos is a widely used insecticide in recent years, and it will produce adverse effects on soil when applied on crops or mixed with soil. In this study, nested polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) were combined to explore the bacterial and fungal community successions in soil treated with 5 and 20 mg/kg of chlorpyrifos. Furthermore, isolates capable of efficiently decomposing chlorpyrifos were molecular-typed using enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Under the experimental conditions, degradation of chlorpyrifos in soil was interpreted with the first-order kinetics, and the half-lives of chlorpyrifos at 5 and 20 mg/kg doses were calculated to be 8.25 and 8.29 d, respectively. DGGE fingerprint and principal component analysis (PCA) indicated that the composition of the fungal community was obviously changed with the chlorpyrifos treatment, and that samples of chlorpyrifos treatment were significantly separated from those of the control from the beginning to the end. While for the bacterial community, chlorpyrifos-treated soil samples were apparently different in the first 30 d and recovered to a similar level of the control up until 60 d, and the distance in the PCA between the chlorpyrifos-treated samples and the control was getting shorter through time and was finally clustered into one group. Together, our results demonstrated that the application of chlorpyrifos could affect the fungal community structure in a quick and lasting way, while only affecting the bacterial community in a temporary way. Finally, nine typical ERIC types of chlorpyrifos-degrading isolates were screened.

Brassinosteroids promote metabolism of pesticides in cucumber.

Brassinosteroids (BRs) are known to protect crops from the toxicity of herbicides, fungicides and insecticides. It is shown here that application of 24-epibrassinolide (EBR) accelerated metabolism of various pesticides and consequently reduced their residual levels in cucumber ( Cucumis sativus L). Chlorpyrifos, a widely used insecticide, caused significant reductions of net photosynthetic rate (Pn) and quantum yield of PSII (Phi(PSII)) in cucumber leaves. EBR pretreatment alleviated the declines of Pn and Phi(PSII) caused by chlorpyrifos application, and this effect of EBR was associated with reductions of chlorpyrifos residues. To understand how EBR promotes chlorpyrifos metabolism, the effects of EBR on activity and expression of enzymes involved in pesticide metabolism were analyzed. EBR had a positive effect on the activation of glutathione S-transferase (GST), peroxidase (POD), and glutathione reductase (GR) after treatment with chlorpyrifos, although the effect on GR was attenuated at later time points when plants were treated with 1 mM chlorpyrifos. In addition, EBR enhanced the expression of P450 and MRP, which encode P450 monooxygenase and ABC-type transporter, respectively. However, the expression of GST was consistently lower than that of plants treated with only chlorpyrifos. Importantly, the stimulatory effect of EBR on pesticide metabolism was also observed for cypermethrin, chlorothalonil, and carbendazim, which was attributed to the enhanced activity and genes involved in pesticide metabolism. The results suggest that BRs may be promising, environmentally friendly, natural substances suitable for wide application to reduce the risks of human and environment exposure to pesticides.

Effects of calcium cyanamide on soil microbial communities and Fusarium oxysporum f. sp. cucumberinum.

Calcium cyanamide (CaCN(2)) has been one of the potential candidates as soil disinfectant since the restriction of methyl bromide in soil fumigation due to its ecological risk. However, little information is available on effects of CaCN(2) on soil microbial community. In this study, the soil microbial communities and the fate of pathogen Fusarium oxysporum (Schlechtend, Fr) f. sp. cucumberinum (Owen) Snyder and Hansen (F.O. f. sp. cucumberinum) in response to CaCN(2) treatment was evaluated. F.O. f. sp. cucumberinum population in soil treated with CaCN(2) at rates of 80 and 200 gm(-2) was suppressed by 88.7 and 92.2% after 15 d of CaCN(2) application. Bacterial, fungal, and actinomycete populations were also greatly decreased after 3 d of CaCN(2) application, but they recovered to the control level by 15 d. The variation in functional diversity of soil microbes characterized by principal component analysis, diversity and evenness indices based on Biolog data followed a similar trend. Meanwhile, the band number from the DGGE of soil 16S rDNA fragments increased from 9 for the non-CaCN(2)-treated soil to 10 or 12 after different rates of CaCN(2) application at 15 d, indicating the increase of abundant rDNA types in the community. The results suggest that CaCN(2) application had only a short-term and transitory impact on the indigenous soil microbial community in contrast to the long-term suppression of the F.O. f. sp. cucumberinum population. It is feasible to reduce Fusarium wilt without significant impact on microbial community by application of CaCN(2) at reasonable doses.

[The effect of thalidomide in preventing delayed nausea and vomiting induced by GP regimen of chemotherapy for non-small cell lung cancer].

OBJECTIVE: To observe the effect of thalidomide in preventing nausea and vomiting induced by emetogenic cisplatin (CDDP) chemotherapy in patients with advanced non-small cell lung cancer. METHODS: This study was carried out as a prospective, randomized control clinical trial. 61 patients with advanced non-small cell lung cancer were scheduled to receive chemotherapy (gemcitabin 1000 mg/m(2) i.v. gtt d1, 8 and CDDP 75 mg/m(2) i.v. gtt d1, GP regimen). The patients were randomly divided into a treatment and control groups. All patients in both groups received ramosetron 0.3 mg intravenously (i.v.) and metoclopramide 20 mg intramuscularly (i.m.) 30 min prior to chemotherapy to prevent nausea and emesis on day 1. In the treatment group, addition of thalidomide (50 mg p.o. bid) were administered on days 1 to 5 after the start of chemotherapy. RESULTS: Acute nausea was effectively controlled in 74.2% of the patients in the control group and in 90.0% of treatment group. Acute vomiting was effectively controlled in 90.3% of the patients in the control group and in 93.3% of treatment group. No statistically significant differences showed in effective control of acute nausea and vomiting between the 2 groups (P = 0.108; P = 1.000). Delayed nausea was effectively controlled in 19.4% of the patients in control group and in 56.7% in the treatment group. Delayed vomiting was effectively controlled in 48.4% of the patients in control group and 76.7% in treatment group. Statistically there was a significant differences in effective control of delayed nausea and vomiting between the 2 groups (P = 0.003, P = 0.023). Both antiemetic regimens were well tolerated, and no significant difference was observed in adverse events between the 2 groups (P > 0.05). CONCLUSION: Our results demonstrate that thalidomide is highly effective in controlling delayed nausea and vomiting episodes in patients induced by moderately emetogenic chemotherapy. Moreover, no serious toxic effects are induced by this treatment.

Residual dynamics of thiacloprid in medical herbs marjoram, thyme, and camomile in soil.

Thiacloprid is a new insecticide of the chloronicotinyl family. To assess its risk after application, residual characteristics of thiacloprid in marjoram, thyme, and camomile and in soil were studied under field conditions. The active ingredient was extracted from the plant material using a mixture of acetone-water. After filtration, the extract was concentrated to the aqueous phase, diluted with water, and portioned against ethyl acetate on a matrix solid phase dispersion column. Thiacloprid was extracted from soil using a mixture of methanol-water, filtered, and reextracted (clean up) with dichloromethane. The residues were quantified using HPLC-MS-MS. The methods were validated by recovery experiments. Thiacloprid residues in marjoram, thyme, and camomile and in soil persisted beyond 10, 14, 14, and 21 d but no residues were detected after 14, 21, 21, and 28 d, respectively. The data obtained in this study indicated that the biexponential model is more suitable than the first-order function to describe the decline of thiacloprid in fresh marjoram, fresh thyme, and dried camomile flowers with half-life (t1/2) of 1.1, 0.7, and 1.2 d, respectively. However, both the first-order function and biexponential model were found to be applicable for dissipation of thiacloprid in soil with almost the same t1/2 values of 3.5 and 3.6 d. The results indicated that thiacloprid dissipates rapidly and does not accumulate in the tested herbs and in soil.

Responses of soil microorganisms and enzymes to repeated applications of chlorothalonil.

Introduction of anthropogenic chemicals into soil may have lasting effects on soil microbial activities and thus soil health. This study was conducted with chlorothalonil to evaluate its effects on soil bacterial, fungal, and actinomycete populations and soil enzymes (acid phosphatase, alkaline phosphatase, urease, catalase, and invertase) after repeated applications. After the first addition of chlorothalonil, the soil bacterial and actinomycete populations were significantly reduced, whereas the population of soil fungi was unchanged. The most marked inhibition on soil microorganisms was observed after the second pesticide addition. However, after initial variations, soil bacteria, fungi, and actinomycetes adapted gradually to chlorothalonil, and the negative effects became transient and weaker following the third and fourth treatments. The inhibitory effect of repeated chlorothalonil applications on soil enzymes followed a similar trend to that on soil microorganisms. Repeated chlorothalonil applications did not result in significant changes in its persistence. Three bacterial strains capable of utilizing chlorothalonil as a sole source of carbon and energy for growth were isolated 21 days after the fourth treatment with chlorothalonil, which indicated that the capability of soil microorganisms for degrading chlorothalonil was formed during the experiment.

Dissipation of chlorpyrifos in pakchoi-vegetated soil in a greenhouse.

The dissipation of chlorpyrifos in pakchoi-vegetated soil was investigated in the summer and autumn in a greenhouse and field, respectively. The dissipation of chlorpyrifos in pakchoi-grown soil was comparatively described by fitting the residue data to seven models (1st-order, 1.5th-order, 2nd-order, RF 1st-order, RF 1.5th-order, RF 2nd-order, and bi-exponential or two-compartment models). Statistical analysis was performed using the SPSS 11.5 statistical package. The bi-exponential model was selected as the optimal model according to the coefficient of determination r2. The dissipation half-lives (DT50) of chlorpyrifos in pakchoi-vegetated soil at the recommended dose in the summer and autumn, calculated by the bi-exponential model, were 0.6 and 1.2 d in a greenhouse, 0.4 and 1.0 d in a field, respectively; the corresponding values at double dose were 1.2 and 2.1 d in a greenhouse, 0.5 and 1.3 d in a field, respectively. The kinetic data indicate the dissipation of chlorpyrifos in pakchoi-grown soil in a greenhouse is slower than that in a field, and dissipates slower in the autumn than in the summer.

Characterization of a fungal strain capable of degrading chlorpyrifos and its use in detoxification of the insecticide on vegetables.

A fungal strain capable of utilizing chlorpyrifos as sole carbon and energy sources was isolated from soil by enrichment cultivation approach. The half-lives of degradation (DT(50)) for chlorpyrifos at concentrations of 1, 10, and 100 mg l(-1) by the fungal strain DSP in mineral salt medium were measured to be 2.03, 2.93, and 3.49 days, respectively. Two cell-free extracts [E (1:10) and E (1:20)] from the fungal strain DSP in bran-glucose medium were prepared and used to enhance chlorpyrifos degradation on vegetables. Compared with the controls, the DT(50) of chlorpyrifos were reduced by 70.3%, 65.6%, 80.6%, 80.6%, and 86.1%, and by 53.8%, 43.2%, 66.0%, 54.3%, and 67.7% on E (1:20) and E (1:10) treated pakchoi, water spinach, Malabar spinach, haricot beans, and pepper, respectively. The 7-day residual values (R (7)) of chlorpyrifos on E (1:10) treated vegetables were all lower than the corresponding maximum residue levels of European Union (EU MRLs), except that the R (7) value on haricot beans was slightly higher than the corresponding EU MRLs. The results indicate that cell-free extracts could rapidly degrade chlorpyrifos residues on vegetables.

An exploration of the relationship between adsorption and bioavailability of pesticides in soil to earthworm.

A study was conducted to determine the adsorption/desorption of butachlor, myclobutanil and chlorpyrifos on five soils using a batch equilibration technique and to study the relationship between bioavailability to Allolobophora caliginosa and the adsorption/desorption of these three pesticides. The results showed that the adsorption/desorption processes of the tested compounds were mainly controlled by soil organic matter content (OM) and octanol/water-partitioning coefficient (K(ow)), and that the bioavailability of the pesticides was dependent on characteristics of pesticides, properties of soils, and uptake routes of earthworms. Bioconcentration of butachlor and myclobutanil was negatively correlated with Freundlich adsorption constant K(af) and K(df). However, only a slightly positive correlation between bioconcentration and K(af) and K(df) was observed for chlorpyrifos due to its high affinity onto soil.

Dissipation of chlorpyrifos on pakchoi inside and outside greenhouse.

The dissipation of chlorpyrifos on pakchoi inside and outside greenhouse was studied. The decline curve of chlorpyrifos on pakchoi could be described as first-order kinetic. The experimental data showed that both the hermetic environment of greenhouse and season affected dissipation rates of chlorpyrifos on pakchoi. Chlorpyrifos declined faster outside greenhouse than inside greenhouse. Chlorpyrifos residues at pre-harvest time were below the maximum residue limits (MRLs) fixed in China, whereas the values inside greenhouse were higher than those outside greenhouse by almost 50%. The recommended pre-harvest time established under conditions of open field might not always fit to greenhouse production.

Fungal degradation of metsulfuron-methyl in pure cultures and soil.

A fungal strain capable of utilizing metsulfuron-methyl as sole carbon and energy sources was isolated from a metsulfuron-methyl treated soil. The degradation characteristics of metsulfuron-methyl by this fungal strain were investigated in liquid culture and soil. More than 79% of metsulfuron-methyl at concentrations of 0.10 mgl(-1), 1.0 mgl(-1) and 10.0 mgl(-1) in pure culture was degraded by strain MD after incubation for 7 days, whereas only 5.6%, 8.6% and 13.1% of metsulfuron-methyl were degraded at levels of 0.10 mgl(-1), 1.0mgl(-1) and 10.0 mgl(-1) in the controls, respectively. The incorporation of strain MD into soil was found to substantially increase the degradation of metsulfuron-methyl. Degradation was 7.5 and 3.8 times faster in strain MD amended soils than in sterilized and fresh soils. The results show that addition of the isolated strain MD enhances degradation of metsulfuron-methyl in water and soil.