BF3 Complexing Phosphate/Phosphonate Ionic Liquids: Synthesis, Characterization and Thermophysical Properties.

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X=dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid-liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] should be considered as fragile liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (-95.33~-98.46 °C) without melting, considerably low viscosities (33.876~58.117 mPa ⋅ s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).

Elucidation of colon-protective efficacy of diosgenin in experimental TNBS-induced colitis: inhibition of NF-κB/IkB-α and Bax/Caspase-1 signaling pathways.

The aim of present investigation was to elucidate the unrevealed beneficial role of diosgenin against an experimental model of TNBS (2,4,6-trinitrobenzenesufonic acid)-induced ulcerative colitis (UC). Colitis was induced in Sprague-Dawley rats by intrarectal administration of TNBS (in 50% ethanol). Then animals were treated with diosgenin (50, 100, and 200 mg/kg) for 14 days. Various biochemical, behavioral, molecular, and histological analysis was performed. Diosgenin significantly decreased (p < 0.05) TNBS-induced elevated colonic oxido-nitrosative damage, myeloperoxidase, hydroxyproline, mRNA expressions of proinflammatory cytokines (TNF-α, IL-1ß, IL-6, and IFN-γ) and inflammatory markers (iNOs and COX-2) induced by TNBS. Western blot analysis relevated that TNBS-induced up-regulated protein expressions of NF-κB, IκBα, Bax, and Caspase-1 were markedly decreased (p < 0.05) by diosgenin treatment. It also markedly ameliorated the histological insults induced in the colon by TNBS. In conclusion, diosgenin exerts its colon-protective efficacy probably through the inhibition of NF-κB/IkB-α and Bax/Caspase-1 signaling pathways to experimental TNBS-induced ulcerative colitis. ABBREVIATIONS: ANOVA: Analysis of variance; 5-ASA: 5-aminosalicylic acid; Bax: Bcl-2-associated X protein; COX-2: Cyclooxygenase-2; DAI: Disease Activity Index; DMSO: Dimethyl sulfoxide; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; GSH: Glutathione; HP: Hydroxyproline; IAEC: International Animal Ethics Committee; IBD: Inflammatory Bowel Disease; IBS: Inflammatory Bowel Syndrome; IL's: Interleukin's; IFN-γ: Interferon-gamma; IκBα: nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha; iNOs: Inducible nitric oxide synthase; LTB4: Leukotriene B4; MDA: Malondialdehyde; MPO: Myeloperoxidase; NO: Nitric Oxide; NF-κB: Nuclear Factor-κB; ROS: Reactive Oxygen Species; SOD: Superoxide Dismutase; TNBS: Trinitrobenzene Sulfonic Acid; TNF-α: Tumor necrosis factor-α.

A Meta-Analysis of Patellar Replacement in Total Knee Arthroplasty for Patients With Knee Osteoarthritis.

BACKGROUND: This meta-analysis (MA) aims at comparing the clinical outcomes of resurfacing and nonresurfacing the patella in patients undergoing total knee arthroplasty in the treatment of knee osteoarthritis. METHODS: Randomized controlled trials were included by retrieving data from electronic English databases. Both fixed and random-effects models were employed, and standardized mean difference and 95% confidence intervals were calculated. Stata13.1 software was used for statistical analysis for all the studies included to compare the differences in improving Knee Society Clinical Score and Knee Society Function Score as well as the reduction in rates of infection, reoperation, and anterior knee pain. RESULTS: A total of 394 studies were initially included in this MA. About 20 randomized controlled trials which met the inclusion criteria were finally enrolled in this MA. The results of our MA showed that the reoperation rate of the patellar resurfacing group was lower than that of the nonresurfacing group. The subgroup analysis was performed according to the follow-up time and revealed that the increase in the Knee Society Clinical Score was higher in the patellar resurfacing group than that in the nonresurfacing group in the follow-up period of 1 to 2 years. The risk of reoperation rate was lower in the patellar resurfacing group than that in the nonresurfacing group, while there were no statistical differences in the follow-up time over 2 years. CONCLUSION: Our study suggests that during the follow-up of 1 to 2 years, patellar resurfacing can significantly increase the Knee Society Clinical Score and reduce the reoperative rates in patients with knee osteoarthritis.

Modulation of phototropic responsiveness in Arabidopsis through ubiquitination of phototropin 1 by the CUL3-Ring E3 ubiquitin ligase CRL3(NPH3).

Plant phototropism is an adaptive response to changes in light direction, quantity, and quality that results in optimization of photosynthetic light harvesting, as well as water and nutrient acquisition. Though several components of the phototropic signal response pathway have been identified in recent years, including the blue light (BL) receptors phototropin1 (phot1) and phot2, much remains unknown. Here, we show that the phot1-interacting protein NONPHOTOTROPIC HYPOCOTYL3 (NPH3) functions as a substrate adapter in a CULLIN3-based E3 ubiquitin ligase, CRL3(NPH3). Under low-intensity BL, CRL3(NPH3) mediates the mono/multiubiquitination of phot1, likely marking it for clathrin-dependent internalization from the plasma membrane. In high-intensity BL, phot1 is both mono/multi- and polyubiquitinated by CRL3(NPH3), with the latter event targeting phot1 for 26S proteasome-mediated degradation. Polyubiquitination and subsequent degradation of phot1 under high-intensity BL likely represent means of receptor desensitization, while mono/multiubiquitination-stimulated internalization of phot1 may be coupled to BL-induced relocalization of hormone (auxin) transporters.

Discovery of alkoxyl biphenyl derivatives bearing dibenzo[c,e]azepine scaffold as potential dual inhibitors of P-glycoprotein and breast cancer resistance protein.

We recently reported alkoxyl biphenyl derivatives bearing dibenzo[c,e]azepine scaffold as novel P-glycoprotein (P-gp, ABCB1) inhibitors. In this study, their ability to reverse breast cancer resistance protein (BCRP, ABCG2)-mediated multidrug resistance was tested in HEK293/BCRP cells which was BCRP-transfected stable HEK293 cells. It was observed that compounds 4d, 4h, 4i increased mitoxantrone accumulation in HEK293/BCRP cells via inhibiting BCRP efflux function. Notably, the inhibitory activity of 4i was comparable to that of the classical BCRP inhibitor Ko143 at an equimolar concentration. Interestingly, 4i had little inhibitory effect on multidrug resistance-associated protein 1 (MRP1, ABCC1), another drug efflux transporter. These results, together with the previous findings, suggest that 4i may be a dual inhibitor of P-gp and BCRP to warrant further investigation.

[Clinical study of platelet-rich plasma gel in total knee arthroplasty].

OBJECTIVE: To investigate the effect of platelet-rich plasma (PRP) gel in total knee arthroplasty. METHODS: From January 2011 to January 2013, 30 patients of total knee arthroplasty were received PRP (PRP group) and 30 patients won't received PRP(normal saline group).Routine drainage and functional exercise were applied to the two groups after operation. Postoperative drainage volume, inflammatory reaction, grade of wound healed, Hospital for Special Surgery (HSS) Score for knee, the Feller Score for patella and range of motion (ROM) for knee were evaluated.Independent samples t-test, grade data used rank sum test were used to compared two groups. RESULTS: Postoperative drainage volume was (152 ± 22) ml in PRP group and (432 ± 35) ml in normal saline group. Postoperative drainage volume were statistically significant difference between two groups (t = 37.098, P < 0.05). At 4 days after operation, no inflammatory reaction was observed in 27 cases of PRP group and in 24 cases of normal saline group, mid inflammatory reaction in 2 cases of PRP group and in 4 cases of normal saline group, moderate inflammatory reaction in 1 cases of PRP group and in 2 cases of normal saline group.Wound healed by first intention in 30 patients of PRP group and in 29 patients of normal saline group (29/30), by second intention after 3 days of dressing change in 1 patient of normal saline group using 75% alcohol wet compressed. The adverse reaction rate was 3.3%. The average follow-up period was 16 months, ranging from 10 to 24 months. Three months postoperative HSS score for knee, scores of patellar, scores of anterior knee pain and ROM for knee were statistically significant difference in PRP group and normal saline group (t = 2.288, 2.097, 2.630, 2.104; all P < 0.05). Inflammatory reaction, grade of wound healed, final follow-up HSS score for knee, scores of patellar, scores of anterior knee pain and ROM for knee had no statistically significant difference between PRP group and normal saline group (P > 0.05). CONCLUSIONS: Using PRP gel in total knee arthroplasty can reduce postoperative drainage volume, accelerate the healing of operation incision with no extra complications.It has good short-term clinical effect.

Synthesis, Characterization, and Physicochemical Properties of New [Emim][BF3X] Complex Anion Ionic Liquids.

A new series of complex anion ionic liquids (ILs) [Emim][BF3X] (X = CH3SO3, EtSO4, HSO4, Tosylate) were synthesized and characterized by nuclear magnetic resonance, elemental analysis, differential scanning calorimetry analysis, and thermogravimetry. The physicochemical properties of these ILs, such as density, viscosity, conductivity, and surface tension, were measured and correlated with thermodynamic and empirical equations in the temperature range of 293.15-358.15 K under ambient conditions, and the thermal expansion coefficient, standard molar entropy, lattice potential energy, viscosity activation energy, surface enthalpy, and surface entropy were further calculated from experimental values. According to the temperature-dependent viscosity and conductivity, [Emim][BF3X] ILs follow the Walden rule, and they are classified as "good (or super) ionic liquids".

Phytochemical composition of Tibetan tea fermented by Eurotium cristatum and its effects on type 1 diabetes mice and gut microbiota.

"Golden-flower" Tibetan tea (GTT) is an innovative dark tea fermented via fungus Eurotium cristatum. To study GTT effects on alleviating the symptoms of type 1 diabetes mellitus (T1DM), GTT's extract (GTTE) was prepared. GTTE chemical compositions were analyzed via HPLC, pyrolysis-gas chromatography-mass (Py-GC-MS) spectrometry analysis, and chemistry analyses. GTTE effects on T1DM were explored on T1DM mice model induced by streptozotocin (STZ). GTTE was composed mainly of tea pigment theabrownin (TB) (49.18%), with high percentages of polysaccharide (16.93%), protein (10.15%), polyphenols (13.90%), amino acids (5.89%), caffeine (1.83%), and flavonoids (0.67%). Py-GC-MS results exhibited that GTTE constituted of phenols, lipids, sugars, and proteins. GTTE attenuated T1DM conditions of mice, relieved their liver and pancreatic injury, restored damaged islet cells, decreased oxidative stress by increasing superoxide dismutase (SOD) and catalase (CAT) levels, modulated cytokine expression leading to the decreasing pro-inflammatory cytokines TNF-α and IL-6, increased anti-inflammatory cytokines IL-4 to improve inflammatory responses, and optimized gut microbiota composition and structure based on high-throughput 16S rDNA sequencing, suggesting multi-channel anti-diabetes mechanisms.

Wilms tumor gene on X chromosome (WTX) inhibits degradation of NRF2 protein through competitive binding to KEAP1 protein.

WTX is a tumor suppressor protein that is lost or mutated in up to 30% of cases of Wilms tumor. Among its known functions, WTX interacts with the ß-transducin repeat containing family of ubiquitin ligase adaptors and promotes the ubiquitination and degradation of the transcription factor ß-catenin, a key control point in the WNT/ß-catenin signaling pathway. Here, we report that WTX interacts with a second ubiquitin ligase adaptor, KEAP1, which functions to regulate the ubiquitination of the transcription factor NRF2, a key control point in the antioxidant response. Surprisingly, we find that unlike its ability to promote the ubiquitination of ß-catenin, WTX inhibits the ubiquitination of NRF2. WTX and NRF2 compete for binding to KEAP1, and thus loss of WTX leads to rapid ubiquitination and degradation of NRF2 and a reduced response to cytotoxic insult. These results expand our understanding of the molecular mechanisms of WTX and reveal a novel regulatory mechanism governing the antioxidant response.

MicroRNA-15a/ß1,4-GalT-I axis contributes to cartilage degeneration via NF-κB signaling in osteoarthritis.

OBJECTIVE: Osteoarthritis is a condition characterized by articular cartilage degradation. The increased expression of ß1,4-Galactosyltransferase-I (ß1,4-GalT-I) in the articular cartilage of osteoarthritis patients was related to an inflammatory response. The aim of this study was to elucidate the role of ß1,4-GalT-I in osteoarthritis. This study aimed to determine the function of 1,4-GalT-I in osteoarthritis. METHODS: The osteoarthritis mouse model with the destabilization of the medial meniscus was established by microsurgical technique. Pathological changes in articular cartilage were observed by hematoxylin and eosin staining and safranin O-fast green staining. Quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays were used to observe mRNA and protein expression, respectively. RNA interactions were verified by a luciferase reporter assay. SA-ß-Gal staining was used to assess chondrocyte senescence. Immunofluorescence staining was conducted to observe the localization of Nuclear Factor-kappaB (NF-κB). RESULTS: ß1,4-GalT-I and microRNA-15a (miR-15a) show high and low expression in the articular cartilage of osteoarthritis, respectively. MiR-15a inhibits the mRNA translation of ß1,4-GalT-I. ß1,4-GalT-I promotes extracellular matrix degradation, senescence, and NF-κB activation in IL-1ß-stimulated chondrocytes, which can be reversed by overexpression of miR-15a. Intra-articular injection of microRNA-15a ameliorates cartilage degeneration by inhibiting ß1,4-GalT-I and phosphorylation of NF-κB in vivo. CONCLUSION: The authors clarified that the miR-15a/ß1,4-GalT-I axis inhibits the phosphorylation of NF-κB thereby inhibiting extracellular matrix degradation and senescence in chondrocytes to alleviate cartilage degeneration in osteoarthritis. MiR-15a and ß1,4-GalT-I may serve as potentially effective targets for the future treatment of osteoarthritis.

[Effectiveness of arthroscopic binding fixation using suture through single bone tunnel for posterior cruciate ligament tibial insertion fracture in adults].

Objective: To explore the effectiveness of arthroscopic binding fixation using suture through single bone tunnel for posterior cruciate ligament (PCL) tibial insertion fractures in adults. Methods: Between October 2019 and October 2021, 16 patients with PCL tibial insertion fractures were treated with arthroscopic binding fixation using suture through single bone tunnel. There were 11 males and 5 females with an average age of 41.1 years (range, 26-58 years). The fractures were caused by traffic accident in 12 cases and sports in 4 cases. The time from injury to operation ranged from 2 to 10 days with an average of 6.0 days. The fractures were classified as Meyers-McKeever type Ⅱ in 4 cases and type Ⅲ in 9 cases, and Zaricznyi type Ⅳ in 3 cases. There were 2 cases of grade Ⅰ, 7 cases of grade Ⅱ, and 7 cases of grade Ⅲ in the posterior drawer test. There were 3 cases combined with lateral collateral ligament injury and 2 cases with meniscus injury. The visual analogue scale (VAS) score, Lysholm score, International Knee Documentation Committee (IKDC) score, and knee range of motion were used to evaluate knee joint function. The posterior drawer test and knee stability tester (Kneelax 3) were used to evaluate knee joint stability. The X-ray films were used to evaluate fracture reduction and healing. Results: All incisions healed by first intention after operation. There was no incision infection, popliteal neurovascular injury, or deep venous thrombosis of lower limbs. All patients were followed up 6-12 months, with an average of 10 months. X-ray films at 6 months after operation showed the fractures obtained bone union. There were 11 cases of grade 0, 4 cases of gradeⅠ, and 1 case of grade Ⅱin posterior drawer test, showing significant difference when compared with preoperative results ( Z=23.167, P<0.001). The VAS score, Lysholm score, IKDC score, knee range of motion, and the results of Kneelax3 examination all significantly improved when compared with preoperative results ( P<0.05). Conclusion: For adult patients with PCL tibial insertion fractures, the arthroscopic binding fixation using suture through single bone tunnel has the advantages of minimal trauma, good fracture reduction, reliable fixation, and fewer complications. The patient's knee joint function recovers well.

Synthesis and evaluation of nitric oxide-releasing DDB derivatives as potential Pgp-mediated MDR reversal agents in MCF-7/Adr cells.

Novel furoxan-based nitric oxide (NO)-releasing DDB derivatives (7a-j) were synthesized. Compounds 7i and 7j significantly reversed the resistance of MCF-7/Adr cells to doxorubicin in the combination treatment, and markedly increased the intracellular accumulation of doxorubicin probably via inhibiting Pgp-mediated intracellular drug efflux as well as down-regulating doxorubicin-induced Pgp expression. It was demonstrated that NO released by 7i and 7j played an important role in increasing intracellular doxorubicin accumulation and chemo-sensitizing MCF-7/Adr cells to doxorubicin, and the synergic effects of DDB and NO-donor moieties in 7i and 7j may contribute to reversing Pgp-mediated MDR in MCF-7/Adr cells to doxorubicin.

Synthesis and evaluation of substituted dibenzo[c,e]azepine-5-ones as P-glycoprotein-mediated multidrug resistance reversal agents.

A series of substituted dibenzo[c,e]azepine-5-ones (7a-h) were synthesized and evaluated as P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) reversal agents. The most potent compound 7h could significantly and selectively enhance the chemo-sensitivity of drug-resistant K562/A02 cells to the cytotoxic effect of adriamycin (ADR) in a dose-dependent manner. Further studies indicated that 7h could markedly increase intracellular accumulation of both rhodamine 123 and ADR in K562/A02 cells and inhibit their efflux from the cells. And 7h had little effect on the levels of P-gp mRNA and protein in K562/A02 cells. These results suggest that the anti-MDR effect of 7h might be attributed to the inhibition of drug efflux function of P-gp, leading to the increased drug accumulation in K562/A02 cells, and thus the compound could be served as a lead for developing P-gp-mediated MDR reversal agents.

Synthesis and biological evaluation of bifendate-chalcone hybrids as a new class of potential P-glycoprotein inhibitors.

Overexpression of P-glycoprotein (P-gp) is one of the major problems to successful cancer chemotherapy. To find novel effective P-gp inhibitors, a series of bifendate-chalcone hybrids were synthesized and evaluated. Among them, the most active compound 8g had little intrinsic cytotoxicity (IC(50)>200 µM), and could increase accumulation of Rhodamine 123 in K562/A02 cells more potently than bifendate and verapamil (VRP) by inhibiting P-gp efflux function. And 8g displayed potent chemo-sensitizing effect and persisted for much longer time (>24h) compared with VRP (<6h). In addition, 8g, unlike VRP, showed no stimulation on the P-gp ATPase activity, suggesting it is not a P-gp substrate. Therefore, 8g may represent a promising lead to develop MDR reversal agents for cancer chemotherapy.

miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells. METHODS: The mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2. RESULTS: RT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3'-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of ß-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition. CONCLUSION: In sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway.

Research on automatic labeling of imbalanced texts of customer complaints based on text enhancement and layer-by-layer semantic matching.

Due to its potential impact on business efficiency, automated customer complaint labeling and classification are of great importance for management decision making and business applications. The majority of the current research on automated labeling uses large and well-balanced datasets. However, customer complaint labels are hierarchical in structure, with many labels at the lowest hierarchy level. Relying on lower-level labels leads to small and imbalanced samples, thus rendering the current automatic labeling practices inapplicable to customer complaints. This article proposes an automatic labeling model incorporating the BERT and word2vec methods. The model is validated on electric utility customer complaint data. Within the model, the BERT method serves to obtain shallow text tags. Furthermore, text enhancement is used to mitigate the problem of imbalanced samples that emerge when the number of labels is large. Finally, the word2vec model is utilized for deep text analysis. Experiments demonstrate the proposed model's efficiency in automating customer complaint labeling. Consequently, the proposed model supports enterprises in improving their service quality while simultaneously reducing labor costs.

Reconstruction of circRNA-miRNA-mRNA associated ceRNA networks reveal functional circRNAs in intracerebral hemorrhage.

Circular RNA (circRNA), a novel class of noncoding RNAs, has been used extensively to complement transcriptome remodeling in the central nervous system, although the genomic coverage provided has rarely been studied in intracerebral hemorrhage (ICH) and is limited and fails to provide a detailed picture of the cerebral transcriptome landscape. Here, we described sequencing-based transcriptome profiling, providing comprehensive analysis of cerebral circRNA, messenger RNA (mRNA) and microRNA (miRNA) expression in ICH rats. In the study, male Sprague-Dawley rats were subjected to ICH, and next-generation sequencing of RNAs isolated from non-hemorrhagic (Sham) and hemorrhagic (ICH) rat brain samples collected 7 (early phase) and 28 (chronic phase) days after insults, was conducted. Bioinformatics analysis was performed to determine miRNA binding sites and gene ontology of circRNAs, target genes of miRNAs, as well as biological functions of mRNAs, altered after ICH. These analyses revealed different expression profiles of circRNAs, mRNAs and miRNAs in day-7 and day-28 ICH groups, respectively, compared with the Sham. In addition, the expression signature of circRNAs was more sensitive to disease progression than that of mRNAs or miRNAs. Further analysis suggested two temporally specific circRNA-miRNA-mRNA networks based on the competitive endogenous RNA theory, which had profound impacts on brain activities after ICH. In summary, these results suggested an important role for circRNAs in the pathogenesis of ICH and in reverse remodeling based on self-protection support, providing deep insights into diverse possibilities for ICH therapy through targeting circRNAs.

Analysis of Heavy Metal Pollution in Cultivated Land of Different Quality Grades in Yangtze River Delta of China.

The distribution of heavy metal pollution in cultivated land is closely related to the quality of the cultivated land. In this study, 533 soil samples were collected from cultivated land in the Yangtze River delta region in China for Cd, Pb, and Hg analyses. Spatial statistical analysis was used to study the heavy metal pollution in the cultivated land, and the driving forces of heavy metal distribution in different cultivated land quality subdivisions were analyzed with GeogDetector. The conclusions are as follows: (1) Among the three heavy metals in the study area, the coefficient of variation of Cd is the largest, and that of Pb is the smallest. The proportion of Cd and Hg exceeding the standard value (the standard of level two in GB 15618-2018) is relatively large, both of which are 5%; (2) From the perspective of the spatial distribution of soil heavy metal pollution, only four counties (CX, HN, WY, and LH) were free of heavy metal pollution. Soil heavy metal pollution in AJ, SY, QJ, and DS counties is relatively serious, and the pollution may come from agricultural activities, manufacturing, and prevalent coastal shipping industries in these counties; (3) The heavy metal pollution levels of cultivated land with different quality levels are different. The high-quality cultivated land has no high contamination, while the medium and the general cultivated land both have high contamination. High contamination is related to Cd for medium and general cultivated lands, and to Hg in only general cultivated land; (4) The main driving factors of heavy metal concentration in cultivated soil were GDP, followed by soil organic matter, and pH. These results indicate that the spatial distribution of heavy metal concentration in cultivated soil was affected by the level of economic development, followed by the ecological environment, indicating that human activities had a critical impact on the ecological environment of cultivated land.

Metal-free catalytic hydrocarboxylation of hexafluorobut-2-yne.

An efficient method for stereoselective synthesis of trifluorinated enol esters catalyzed by base was introduced. The DFT calculations and experimental results both supported the nucleophilic addition process. The protocol featured mild reaction conditions and showed a wide functional group tolerance. The one-pot simultaneous etherification and esterification of the salicylic acids further demonstrated the prospective synthetic application.

Multiple affinity states of cGMP-specific phosphodiesterase for sildenafil inhibition defined by cGMP-dependent and cGMP-independent mechanisms.

cGMP-specific phosphodiesterase (PDE5) has become a target for drug development for the treatment of a number of physiological dysfunctions, affected by changes in the cGMP/cGMP-dependent protein kinase (PKG) signaling pathway. PDE5 has two highly homologous regulatory domains, GAF-A and GAF-B. We showed previously that PDE5 could be converted from a low-activity (nonactivated) state to a high-activity state upon cGMP binding to the GAF-A domain with higher sensitivities toward sildenafil (EMBO J 22:469-478, 2003). Here we investigated whether sildenafil sensitivity of PDE5 could be modified by cGMP-independent mechanisms. Individually expressed recombinant GAF-A and GAF-B proteins were tested for their ability to modulate full-length recombinant PDE5 affinity to sildenafil. The GAF-A domain protein had the most dramatic effect on the affinity of the nonactivated recombinant PDE5 for sildenafil, revealing much higher sensitivity to sildenafil inhibition. The apparent affinity for sildenafil increased from the nanomolar range to the picomolar range, providing evidence for the presence of a "super-high" sensitivity state of PDE5 for sildenafil inhibition. In human platelet, higher sensitivity of PDE5 for sildenafil inhibition has been detected after blocking cGMP-binding sites of the GAF-A domain. Thus, our data demonstrate that high sensitivity of PDE5 for sildenafil can be obtained not only through cGMP-induced activation of PDE, but also through cGMP-independent modulation of PDE5 in the nonactivated state, possibly through protein-protein interaction. Furthermore, data suggest that nonactivated PDE5 with "super-high" affinities for sildenafil inhibition may be responsible for therapeutic effects of long-term treatments with low doses of PDE5 inhibitors.