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Benign main bronchial stenosis may cause a potentially life-threatening condition. Airway silicone stenting is an important option of bronchoscopic treatments for patients with main bronchial stenosis. However, stent migration is one of the most frequent complications, which require repeated bronchoscopic interventions. To resolve this issue, we therefore in the report described a novel designed V-shaped silicone stent for the treatment of unilateral main bronchial stenosis. This method may be widely applied to clinical practice to prevent stent migration.

Palladium-catalyzed oxidative formal [4+1] annulation of pyridine-substituted acrylonitriles toward divergent fused N-heterocycles synthesis is reported. The heterodifunctionalization reaction with Cu(OAc)2 and urea as the nitrogen source accesses to nitrile-substituted pyrazolo[1,5-a]pyridines in moderate to good yields, while the homodifunctionalization reaction with FeBr3 leads to synthesis of nitrile-substituted indolizines in excellent yields.

Xiaoer-Feire-Kechuan (XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation. The complicated composition rendered its chemical analysis and effective-component elucidation. In this study, we combined quantitative analysis and bioactivity test to reveal the anti-inflammatory constituents of XFK. First, UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes (covering 9 out of 11 herbs) in different XFK formulations. Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity. Then, anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay. Finally, major analytes forsythosides H, I, A (8–10), and baicalin (15) (total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities (inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK. The present study provided an effective strategy to discover effective constituents of multi-herb formulas., Graphical abstract Image 1, Highlights ∙ Effective components were elucidated for XFK, a 11-herb formula. ∙Contents of 35 compounds were determined using UPLC-DAD and UHPLC/Q-Orbitrap-MS. ∙Parallel Reaction Monitoring mode was used to improve the sensitivity. ∙COX-2 inhibition assay was used to evaluate the bioactivity of 35 compounds. ∙Five major compounds were proposed as anti-inflammatory constituents for XFK.

Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.

In order to dispose of high level nuclear waste during the operation of underground geological repositories, the buffer/backfill performance of bentonite–based material might be affected by the combined influence of temperature field and infiltrating groundwater thereby leading to uncertainties in the safe operation of repositories. In order to address this issue, bentonite–sand mixtures (BSM) were prepared by mixing GMZ01 bentonite with sand using ratios of 70:30 and 30:70 by weight. One-dimensional deformation experiments were conducted on the prepared BSM in NaCl solutions of varying concentrations (0, 0.1, and 1.0 mol/L) at three different temperatures (25, 60, and 90 °C). The experimental results on the BSM in NaCl solutions indicated that the swelling deformation increased as temperature rises, because osmotic swelling is the dominant swelling type under the experimental conditions. The swelling deformation of BSM could be represented by fractal em–pe relation (em is the montmorillonite void ratio, pe is the effective stress incorporating osmotic suction). At each temperature interval, the swelling of BSM with high bentonite content in different NaCl solutions can be expressed as a unique em–pe relation; however, the swelling coefficient of montmorillonite in the em–pe relationship increases at higher temperature. When the effective stress pe exceeds a threshold, sand–particle skeletons will be formed in BSM with low bentonite content, thus resulting in deviations in the value of em from the em–pe curve. The em–pe relation offers a simple and efficacious method to estimate the deformation of BSM under combined thermal–salt effects.

In high demand is developing trifunctional electrocatalysts to simultaneously drive hydrogen evolution reaction (HER) and oxygen evolution/reduction reaction (OER/ORR) for metal-air batteries and water splitting. Here we develop the carbon nanotubes (CNTs)-grafted FeC/MnO2 nanocomposite catalyst by carbonizing FeMn metal-organic frameworks. The synergistic effect between FeC and MnO2 dominantly contributes the ORR, OER, and HER. The transition metal-mediated growth of CNTs by an in-situ catalysis mechanism enables high electrical conductivity, abundant active sites, as well as efficient reaction pathways. The optimized chemical composite and unique hierarchical structure endow the FeC/MnO2 with low overpotentials for multiply electrochemical reactions. Consequently, the composite catalyst successfully serves as the bifunctional electrode for water splitting with a voltage of 1.66 V at 10 mA cm−2 as well as the cathode for all-solid-state metal-air battery with Pt/C-comparable performance. The advanced transition metal composite presented in this work provides the guidance for rationally developing trifunctional electrocatalysts for efficient integrated energy conversion systems.

Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils., Asthma: A physiological cannabinoid promotes inflammation Oleoylethanolamide (OEA), an endocannabinoid similar to those found in cannabis, occurs naturally in the body, and has now been implicated in promoting symptoms of asthma. OEA activates white blood cells called eosinophils and ILC2 cells, which are both parts of our immune response. Researchers in South Korea, led by Ga-Young Ban at Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, studied the effect of OEA on respiratory system cells from people with asthma and in mice used to model the condition in humans. OEA-induced inflammatory responses associated with asthma by stimulating the release of signaling molecules called cytokines. However, some other endocannabinoids have anti-inflammatory effects. Studying the effects of all endocannabinoids could yield new insights into asthma, with this study opening new possibilities for treating asthma by interfering with OEA-induced signaling responses.

Chemodynamic therapy (CDT), as the emerging modality of cancer therapy based on Fenton or Fenton-like reactions, still suffers from low efficacy of hydroxyl radical generation, which requires full exposure of reaction sites of CDT nanoagents to intracellular H

Schaftoside and isoschaftoside are bioactive natural products widely distributed in higher plants including cereal crops and medicinal herbs. Their biosynthesis may be related with plant defense. However, little is known on the glycosylation biosynthetic pathway of these flavonoid di-C-glycosides with different sugar residues. Herein, we report that the biosynthesis of (iso)schaftosides is sequentially catalyzed by two C-glycosyltransferases (CGTs), i.e., CGTa for C-glucosylation of the 2-hydroxyflavanone aglycone and CGTb for C-arabinosylation of the mono-C-glucoside. The two enzymes of the same plant exhibit high homology but remarkably different sugar acceptor and donor selectivities. A total of 14 CGTa and CGTb enzymes were cloned and characterized from seven dicot and monocot plants, including Scutellaria baicalensis, Glycyrrhiza uralensis, Oryza sativa ssp. japonica, and Zea mays, and the in vivo functions for three enzymes were verified by RNA interference and overexpression. Through transcriptome analysis, we found homologous genes in 119 other plants, indicating this pathway is general for the biosynthesis of (iso)schaftosides. Furthermore, we resolved the crystal structures of five CGTs and realized the functional switch of SbCGTb to SbCGTa by structural analysis and mutagenesis of key amino acids. The CGT enzymes discovered in this paper allow efficient synthesis of (iso)schaftosides, and the general glycosylation pathway presents a platform to study the chemical defense mechanisms of higher plants.

Background : : Urgent-start peritoneal dialysis (PD) is applied to patients who need PD within two weeks but are able to wait for more than 48 hours before starting PD. To evaluate the usefulness of percutaneous PD catheter insertion in urgent-start PD, we reviewed the clinical outcomes of percutaneous catheter insertion with immediate start PD and surgical insertion with longer break-in time in Pusan National University Hospital. Methods : : This study included 177 patients who underwent urgent-start PD. Based on the PD catheter insertion techniques, the patients with urgent-start PD were divided into percutaneous (n = 103) and surgical (n = 74) groups. For the percutaneous group, a modified Seldinger percutaneous catheter insertion with immediate initiation of continuous ambulatory PD was performed by nephrologists. Results : : The percutaneous group showed higher serum urea nitrogen, creatinine, and lower serum albumin compared with the surgical group (P < 0.05). Ninety-day infectious and mechanical complications showed no significant differences between the two groups. Ninety-day peritonitis in the percutaneous group was 9.7% compared to 5.4% in the surgical group (P = not significant [NS]). Major leakage was 3.9% in the percutaneous group compared to 1.4% in the surgical group (P = NS). Overall infectious and mechanical complication-free survival was not significantly different between the two groups. The percutaneous group and surgical group showed no statistical difference with respect to catheter survival over the entire observation period (P = NS). Conclusion : : This study suggests that urgent-start PD can be applied safely with percutaneous catheter insertion by nephrologists with no break-in period.

Highly efficient, stable, and low-cost catalysts for electrochemical water splitting play a critical role in promoting energy efficiency in the renewable hydrogen power-related industries. In this study, nonprecious metal carbides composed of Fe3 C and Mo2 C supported by carbon nanoplates are prepared and utilized as bifunctional electrocatalysts for overall water splitting. Spatially confined annealing of the polydopamine-coated metal precursors affords a structure containing porous cubes isolated by carbon nanoplates encapsulated with Fe3 C and Mo2 C nanoparticles. The hybrid electrocatalyst with a hierarchical structure, large surface area, and abundant exposed active sites benefits from efficient mass transport and more importantly the strong charge-transfer effect between the iron and molybdenum moieties. Under strong alkaline conditions, the optimized Fe3 C-Mo2 C hybrid (with a Fe/Mo ratio of 1 : 2) requires a low overpotential of 274 and 301 mV for the electrocatalytic oxygen evolution reaction at current densities of 10 and 100 mA cm-2 , respectively, accompanied with decent hydrogen evolution activity, thereby demonstrating efficient bifunctional electrocatalytic activity towards overall water splitting.

This study aimed to evaluate the effect Cycloastragenol (CAG), a triterpenoid saponin isolated from the Radix astragali, on Aβ-induced BBB damage. An immortalized endothelial cell line (bEnd.3) was...

Purpose The monocarbonyl analogs of curcumin (MCACs) have been widely studied for their promising antitumor activity. Pyrazole is a five-membered aromatic heterocyclic system with various bioactivities incorporated frequently in drugs. However, few of MCACs inspired pyrazole analogues were investigated. To search for more potent cytotoxic agents based on MCACs, a series of new 1,5-diaryl/heteroaryl-1,4-pentadien-3-ones inspired pyrazole moiety was synthesized and evaluated on their anti-colon cancer activities. Methods Fifteen new compounds were synthesized and characterized by spectral datum, and then they were tested preliminarily by MTT assay for their cytotoxic activities against a panel of four human cancer cell lines, namely, gastric (SGC-7901), liver (HepG2), lung (A549), and colon (SW620) cancer cells. Compound 7h exhibited excellent selectivity and outstanding anti-proliferation activity against SW620 cells among these 15 compounds. Further, the mechanisms were investigated by transwell migration and invasion assay, clonogenic assay, cell apoptosis analysis, cell cycle analysis, Western blot analysis. Results The IC50 value of 7h against SW620 cells was 12 nM, being more potent than curcumin (IC50 = 9.36 μM), adriamysin (IC50 = 3.28 μM) and oxaliplatin (IC50 = 13.33 μM). Further assays showed that 7h inhibited SW620 cell migration, invasion and colony formation obviously, which was due to its ability to induce cell cycle arrest in the G2/M and S phases and apoptosis. Western blot assay revealed that 7h decreased the protein expression of ATM gene, which may primarily contribute to its anticancer activity against SW620 cells. Conclusion A new MCACs 7h was synthesized and found to exhibit excellent anti-proliferation activity against SW620 cells. Further studies indicated that 7h exerted its anticancer activity against SW620 cells probably via decreasing the ATM protein expression. The present study suggested that 7h was a promising candidate as an anti-colon cancer drug for future development.

Natural products (NPs) are a rich source of drug discovery, and some of them act by covalently binding to the targets. Recently, targeted covalent natural product (TCNP) design has gained considerable attention since this approach offers significant benefits in improving biological efficacy and decreasing the off-target side effects. However, most of the known TCNPs were discovered by chance. Rational approaches for a systematic screen of TCNPs are much needed. Here, we developed a combined computational and experimental approach to carry out herb-based screening to identify TCNPs against proper cysteine residues in the target proteins. The herb-based TCNP screening approach (HB-TCNP) starts from a druggable pocket and cysteine residue prediction, followed by virtual screening of a covalent NP database and herb-based mapping to identify candidate herbs for experimental validation. Herbs with time-dependent activity are selected, and their NPs are experimentally tested to further screen covalent NPs. We have successfully applied HB-TCNP to screen anti-PLK1 herbs and NPs with high efficacy. Cys67 and Cys133 in the ATP binding pocket of PLK1 were used in the search. Five herbs were tested and exhibited PLK1 inhibition activity to some extent, among which Scutellaria baicalensis showed the most potent activity with time dependency. Further experimental studies showed that the main active compounds in Scutellaria baicalensis, baicalein and baicalin, covalently bind PLK1 through Cys133. Our study provided an efficient way to rationally design TCNPs and to make better use of herb medicines. The Cys133 residue in PLK1 serves as a novel covalent site for further drug discovery against PLK1.

Glycyrrhiza uralensis (liquorice) is a well-known medicinal plant. Its roots and rhizomes are used as the popular Chinese herbal medicine Gan-Cao. An ethanol extract of the aerial parts of G. uralensis showed antidiabetic effects on db/db mice. It decreased the blood glucose level by 30.3% and increased the serum insulin level by 41.8% compared to the control group. Eighty-six phenolic compounds (1-86) were obtained from the aerial parts, including the new prenylated isoflavanones (1-5), isoflavans (6-9), and a 2-phenylbenzofuran (10). The structures were identified by NMR and HRESIMS data analyses, and the absolute configurations were established by comparing the calculated and experimental ECD spectroscopic data. Compounds 2, 6, and 10 inhibited PTP1B with IC50 values of 5.9, 6.7, and 5.3 μM, respectively. Compound 2 and the known compounds glycycoumarin (76) and glyurallin A (79) inhibited α-glucosidase with IC50 values of 20.1, 0.1, and 0.3 μM, respectively. Compound 4 at 10 μM increased the glucose uptake rate to 95% in an insulin resistance HepG2 cell model (p < 0.01).

Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneal injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28 d to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-κB and level of inflammatory factors like tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-κB and mitigating neuroinflammation.

A highly efficient di-C-glycosyltransferase GgCGT was discovered from the medicinal plant Glycyrrhiza glabra. GgCGT catalyzes a two-step di-C-glycosylation of flopropione-containing substrates with conversion rates of >98%. To elucidate the catalytic mechanisms of GgCGT, we solved its crystal structures in complex with UDP-Glc, UDP-Gal, UDP/phloretin, and UDP/nothofagin, respectively. Structural analysis revealed that the sugar donor selectivity was controlled by the hydrogen-bond interactions of sugar hydroxyl groups with D390 and other key residues. The di-C-glycosylation capability of GgCGT was attributed to a spacious substrate-binding tunnel, and the G389K mutation could switch di- to mono-C-glycosylation. GgCGT is the first di-C-glycosyltransferase with a crystal structure, and the first C-glycosyltransferase with a complex structure containing a sugar acceptor. This work could benefit the development of efficient biocatalysts to synthesize C-glycosides with medicinal potential.

In an attempt to discover anticancer triterpenoids from the medicinal fungus Antrodia camphorata, a total of 60 triterpenoids (1–60) including 18 new ones (antcamphins M–X, 1–18) were isolated from its dish cultures. The structures of the new compounds were elucidated by extensive NMR and HRESIMS data analyses. The absolute configurations were established by the modified Mosher's method, chemical transformation, or X-ray crystallographic data analysis. The cytotoxic activities of 1–60, together with previously reported compounds 61–81, were evaluated using four human cancer cell lines (HL60, U251, SW480, and MCF-7 cells). Compound 57 exhibited potent activities against all the four cell lines with IC50 values of 2.6, 8.2, 2.5, and 4.6 μM, respectively. Moreover, the combination of 10 and 69 (20 μM) could remarkably enhance their cytotoxic activities against the HL60 cells of paclitaxel (10 nM), with inhibition rates increasing from 19.6% to 58.2% and 70.6%, respectively.

Antrodia camphorata is a rare and valuable medicinal mushroom. In this work, 11 new triterpenoids, namely, antcamphorols A-K (1-11), together with 10 known triterpenoids, 12-21, were isolated from dish-cultured A. camphorata. Compound 1 is an unprecedented C31 lanostane-type triterpenoid featuring a methyl group at C-15 and a C-21-O-C-24 tetrahydropyran ring at C-17. Compounds 2-11 are ergostane-type triterpenoids, and they include two pairs of norergostanes 2-5. The structures of the new compounds were identified by NMR, 2D NMR, and HRESIMS data analyses. The absolute configurations of 1 and 6 were defined by X-ray diffraction data, and the absolute configuration at C-25 of 4 was determined by the modified Mosher's method. Compounds 7, 9, 10, 16, and 19 showed significant ROS scavenging activities (63.9-70.5% at 20 μM) in high-glucose-induced HUVECs. Compounds 3 and 8 exhibited moderate cytotoxic activities against U251 (IC50, 9.2 μM) and MCF-7 (IC50, 8.1 μM) human cancer cell lines, respectively.

Compacted bentonite has been considered a suitable engineered barrier material for high-level radioactive waste (HLW) repositories for several decades. However, hyperalkaline groundwater produced by cementitious materials, combined with the heat generated by nuclear decay during the long-term storage of waste canisters, may cause the deterioration of the swelling properties of compacted bentonite. In this study, a series of swelling pressure tests and scanning electron microscopy (SEM) tests were performed on compacted Gaomiaozi (GMZ) bentonite (dry density 1.7 Mg/m3) to investigate the deterioration of the swelling pressure. Results indicated that the deterioration of the swelling pressure was facilitated by the temperature when the same concentration of NaOH solution was infiltrated, and a model of swelling pressure deterioration was developed to predict the long-term swelling pressure. Furthermore, the dissolution of montmorillonite and some silicate minerals, as well as the formation of non-expanding secondary minerals, led to transformations of the agglomeration patterns of the soil particles and structural damage to the bentonite, which controlled the long-term deterioration of the swelling pressure. Therefore, for the long-term operation of an HLW repository, the deterioration of the swelling pressure of compacted bentonite should be monitored, and safety assessments should account for the effects of heat and alkalinity.

In a high-level radioactive waste repository, bentonite may react with the alkaline solution produced by cement degradation. In this study, bentonite was mixed with alkaline solution in a closed system and reacted for 3–24 months. Furthermore, swelling tests were conducted on the alkaline-dissolved bentonite immersed in distilled water. The swelling deformation decreased significantly with increases in the concentration of NaOH solution and reaction time, and this was mainly due to montmorillonite dissolution. The fractal e–p relationship (e is the void ratio and p is the vertical pressure) with two calculation coefficients (the swelling coefficient and the fractal dimension) was employed to determine the swelling of alkaline-dissolved bentonite. The fractal dimension increased slightly with increasing reaction time or concentration of NaOH solution, as the dissolution traces caused by the alkaline solution favoured an increase in the irregularity and fractality of the bentonite surface. The swelling coefficient decreased linearly with decreasing montmorillonite content. In addition, the swelling coefficient and the fractal dimension were related exponentially to the reaction time in alkaline solution. A relationship between the swelling of alkaline-dissolved samples and the reaction time was proposed, which might be used to assess the swelling properties of bentonite barriers that would be affected by long-term dissolution of the alkaline solution in a closed repository.

The mineral alteration and microstructure evolution of compacted GMZ bentonite was investigated during the long-term in the Beishan area, a candidate for a high-level radioactive waste repository in China. The compacted GMZ bentonite samples at initial dry densities of 1.5 and 1.7 Mg/m3 were infiltrated by synthetic Beishan Site Water (BSW) and two synthetic cement solutions (Young Cement Water -YCW and Evolved Cement Water - ECW) under constant volume conditions for about 2 months in this study. X-Ray diffractometry (XRD), mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM-EDS) tests were carried out to observe the mineralogy and microstructure of the specimens after experiencing the three types of pore solutions. There is evidence of cation exchange reactions, some zeolites and C-S-H in the GMZ bentonite after the infiltration of alkaline solutions. The hydration of alkaline solutions and mineralogy alteration result in changes to the microstructure of compacted GMZ bentonite. The generated secondary mineral on the surface of montmorillonite leads to the clogging of inter-aggregate pores. In the case of high dry density, this resulted in pore occlusion.

Gaomiaozi (GMZ) bentonite is the most extensively used buffer/backfill material in deep geological repositories used for the disposal of high-level nuclear waste in China. Highly alkaline ground water solutions derived from the cement dissolution may cause changes in the mineralogical composition and in the adsorption capacity of bentonite, and may affect the long-term performance of the engineering barrier system. In the present study, the alteration of montmorillonite and its influence on the adsorptive properties of GMZ bentonite were investigated. The X-ray diffraction patterns of the mineral composition showed that the main compound of the GMZ bentonite is montmorillonite. By contrast, its hydration with a solution of KOH at 80 °C produced cementitious materials, and transformation could likely lead to kaolinisation. Thermodynamic results show that the adsorption of Sr (II) on GMZ bentonite is exothermic and follows quasi-secondary adsorption kinetics. For an initial Sr (II) concentration C0 = 100 mg/L, the maximum amount of Sr (II) adsorbed (qe) on GMZ bentonite was 9.72 mg/g. The adsorption capacity of GMZ bentonite on Sr (II) decreased gradually and as a function of the mineral transformation time in a mixture of GMZ bentonite and KOH. The Freundlich isotherm adsorption model can describe in a satisfactory manner the adsorption of Sr (II) on GMZ bentonite or the transformation of bentonite at different degrees of mineral transformations.

Investigation of the effects of salinity concentration on shear strength of compressed bentonite and its sand mixture is desideratum to evaluate the safety of engineered barriers for disposal of highly radioactive nuclear waste. In this research study, the compacted bentonite–sand mixtures were first saturated using distilled water and NaCl solutions under a specified stress in oedometers. Then the specimens were subjected to shearing in a direct shear apparatus. The experimental results revealed that the shear strength increases at higher NaCl concentration and high sand content of mixture. By employing the modified effective stress (pe) containing the osmotic suction effect of porewater, the highest shear strength (τf), referred to as the peak shear strength (PSS) from hereon, of mixture in different NaCl concentrations can be represented by a unique line in the τf–pe plane. As per Mohr–Coulomb principle, the mixtures with a given bentonite content possess the same parameters of shear strength (effective angle of internal friction φ′ and effective cohesion c′), when they are placed and allowed to saturate in NaCl solution at various concentrations. On the contrary, the appearance of sand particles on the shearing surface offers more resilience to the movement of montmorillonite particles which increases the internal friction angle φ′ but poses negligible effects on the cohesion c′. When the effective stress approaches a threshold value, the skeleton of sand particles is formed in the mixture with high sand content bringing about a significant change in the shear strength of bentonite.

Sphingosine-1-phosphate (S1P) is a phospholipid that regulates pleiotropic biological activities and exerts extracellular functions by binding to five specific G-protein-coupled receptors, S1P receptors (S1PR) 1–5. When activated by S1P, S1PR promote the proliferation and invasion of tumor cells by inducing the formation of new blood vessels. We developed and assessed a new monoclonal antibody imaging probe 99mTc-HYNIC-S1PR1mAb, to explore the feasibility of targeting the S1PR1 in vitro and in vivo. S1PR1mAb was prepared and followed by technetium-99m labeling with succinimidyl 6-hydraziniumnicotinate hydrochloride. Cell uptake and blocking studies were performed to investigate the binding specificity of 99mTc-HYNIC-S1PR1mAb in vitro. 99mTc-HYNIC-S1P1mAb was also tested in vivo in mice xenografted with SK-HEP-1 (high-expression of S1PR1) and MCF-7 (low-expression of S1PR1) using single-photon emission-computed tomography (SPECT). Ex vivo gamma counting of tissues from tumor-bearing mice was used to evaluate 99mTc-HYNIC-S1PR1mAb biodistribution. The biodistribution study results showed significantly higher uptake in SK-HEP-1 tumors than in MCF-7 tumors (P < 0.001). Reduced uptake of 99mTc-HYNIC-S1PR1mAb in SK-HEP-1 was observed in tumor-bearing nude mice pretreated with fingolimod, which binds competitively to the receptors, especially S1PR1. 99mTc-HYNIC-S1PR1mAb can be synthesized and specifically targeted to S1PR1 in vitro and in vivo, allowing S1PR1 expression assessment with SPECT imaging.

Rationale: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN). Patient concerns: A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking. Diagnosis: The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system. Intervention: The patient was advised to take 4 mg of perindopril. Outcome: Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL). Lessons: A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.

A metal-free three-component annulation reaction for the synthesis of indolizine thiones via tandem C-C/C-N/C-S bond formation was developed. Various 2-alkylpyridines with aromatic ynals and elemental sulfur proceeded smoothly under catalyst-free conditions, and the desired products were obtained in moderate to excellent yields.

As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

In our previous studies of the molecular mechanisms of poly(ADP-ribose) polymerase 1 (PARP-1)-mediated transcriptional regulation we identified a novel class of PARP-1 inhibitors targeting the histone-dependent route of PARP-1 activation. Because histone-dependent activation is unique to PARP-1, non-NAD-like PARP-1 inhibitors have the potential to bypass the off-target effects of classical NAD-dependent PARP-1 inhibitors, such as olaparib, veliparib, and rucaparib. Furthermore, our recently published studies demonstrate that, compared to NAD-like PARP-1 inhibitors that are used clinically, the non-NAD-like PARP-1 inhibitor 5F02 exhibited superior antitumor activity in cell and animal models of human prostate cancer (PC). In this study, we further evaluated the antitumor activity of 5F02 and several of its novel analogues against PC cells. In contrast to NAD-like PARP-1 inhibitors, non-NAD-like PARP-1 inhibitors demonstrated efficacy against androgen-dependent and -independent routes of androgen receptor signaling activation. Our experiments reveal that methylation of the quaternary ammonium salt and the presence of esters were critical for the antitumor activity of 5F02 against PC cells. In addition, we examined the role of a related regulatory protein of PARP-1, called Poly(ADP-ribose) glycohydrolase (PARG), in prostate carcinogenesis. Our study reveals that PARG expression is severely disrupted in PC cells, which is associated with decreased integrity and localization of Cajal bodies (CB). Overall, the results of our study strengthen the justification for using non-NAD-like PARP-1 inhibitors as a novel therapeutic strategy for the treatment of advanced prostate cancer.

Licorice (Glycyrrhiza uralensis) is a popular medicinal plant containing more than 70 flavonoid and triterpenoid glycosides. Thus far, only a few reports are available on the glycosylation enzymes involved in their biosynthesis. In this work, we mined the transcriptome data of G. uralensis and discovered 43 candidate genes for O-glycosyltransferase (O-GT). Among them, 17 genes could be expressed in E. coli, and functions of the enzymes were analyzed by catalyzing eight native substrates. As a result, we characterized 11 O-GTs, including isoflavone 7-O-GTs, flavonol 3-O-GTs, and promiscuous O-GTs catalyzing flavones, chalcones, and triterpenoids. They could efficiently synthesize key licorice compounds such as liquiritin, isoliquiritin, ononin, and 3-O-β-d-glucuronosyl glycyrrhetinic acid. The diversity of O-GTs contributes to the biosynthesis of various glycosides in licorice. These enzymes could also be used as biocatalytic tools to synthesize other bioactive O-glycosides.

A Lewis acid-catalyzed three-component annulation reaction of 2-aminopyridines and ynals with elemental sulfur was established. A series of imidazo[1,2-a]pyridine thiones was obtained in moderate to excellent yields. The merits of this transformation include easily available starting materials, multiple C-heteroatom bond formation in one pot, good functional group tolerance, elemental sulfur as S source, operational simplicity, etc.

To study the change mechanisms of the fractal dimension of bentonite affected by a corrosion process in alkaline solution, sodium bentonite was mixed with 1 mol/L NaOH solution and sealed for reaction for up to 720 d (days). The fractal dimensions of bentonite specimens at different stages of the corrosion process were obtained from N2 adsorption and swelling deformation tests, and the results of both methods suggested that the fractal dimension tends to increase with duration of the corrosion process. From X-ray diffraction (XRD) tests, it was found that montmorillonite, the main component of bentonite, was dissolved gradually in the alkaline solution. However, the decline in montmorillonite content had no relation to the change in fractal dimension, which was validated by swelling deformation tests of bentonite–quartz mixtures, as the swelling characteristics of the bentonite–quartz mixtures could be expressed by a unique curve of the em–ps relation (em is the void ratio of montmorillonite, ps is the vertical stress) with an identical fractal dimension. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images were used to observe the surface microscopic morphology of the original and alkaline-corroded bentonite. It was found that montmorillonite layers in the original bentonite were often aggregated into plate-like particles. However, after corrosion in the alkaline solution, these montmorillonite aggregates were cracked into small stacks and the surface of montmorillonite layers became more uneven, resulting in a more complicated surface and a higher fractal dimension.

Aims/Introduction Recently, some data have supported the concept that diabetes is negatively associated with aortic aneurysm. In the present study, we aimed to investigate the relationship between diabetes and cardiac structural and functional characteristics, in particular, aortic root dimensions, in end‐stage renal disease (ESRD) patients. Methods ESRD patients receiving peritoneal dialysis for >3 months were consecutively enrolled. Clinical features and echocardiographic parameters were analyzed according to the presence of diabetes history. Correlation analyses were carried out for diabetes mellitus and aortic root dilatation. Multiple logistic regression analysis was carried out to identify variables correlated with aortic root dilatation. Results A total of 218 ESRD patients receiving peritoneal dialysis were enrolled. Patients with diabetes showed lower left ventricular internal measurements in end‐diastole, left ventricular internal measurements in end‐systole and aortic root diameter (ARD)/body surface area (BSA). Worse cardiac diastolic function was also observed in these patients. In addition, the age‐related increase of ARD/BSA and ARD/height was attenuated in patients with diabetes. With the increase of ARD/BSA, lower levels of serum creatinine, phosphorus and serum glucose, as well as higher serum high‐density lipoprotein cholesterol and apolipoprotein A‐1 were also observed. Increased normalized left ventricular internal measurements were shown in patients with greater ARD/BSA. Multiple regression analysis showed that diabetes (odds ratio 0.353, P = 0.015) was an independent correlate of aortic root dilatation, even after correction for age, sex and other clinical confounders in the enrolled patients. Conclusions The present findings shown an inverse association between diabetes and age‐related aortic root dilatation in ESRD patients. Diabetes remained to be independently correlated with aortic root dilatation even after adjustment for age, sex and other clinical confounders in ESRD patients.

In the deep geological disposal of high-level radioactive wastes (HLW), Na-bentonite produced from Gaomiaozi (GMZ) deposit has been selected as a possible buffer and backfill material for the Beishan repository in China. A sealing buffer is manufactured with bentonite at its hygroscopic water content (initially unsaturated). After taking water from the surrounding geological medium, bentonite under totally free condition is used to seal the technological voids, and then the outer surrounding bentonite (affected by the water mostly) compresses the innermost bentonite under partially free-swelling condition. However, permeability of GMZ bentonite under the partially free-swelling condition is still unknown. In this article, using the instantaneous profile method, we present a laboratory test of the GMZ bentonite unsaturated hydraulic conductivity under partially free-swelling condition. Changes in the cross-sectional area and motion of the sensors (to measure temperature and relative humidity) were considered in computing the unsaturated permeability. Our experimental results show that before the finial hydration stage, although permeability increases locally at some suctions (due to saturation degree increase and bentonite swelling to some extent), unsaturated permeabilities decrease and become constant in general for the reasons as follows. Initially, water is tightly adsorbed to the clay sheet surface and then water film is adsorbed to the tightly adsorbed water which leads to the initial highest permeability, and then diffuse double-layer forces lead to water uptake between the hydrated montmorillonite unit layers which is partially restricted by the confining stress, while capillary water flows on the water adsorbed on the internal surface of the bentonite large pores. For the capillary water flow due to surface tension, complex microstructure evolution (e.g., mesoscopic swelling compacts the inter-aggregate pores due to hydration under the confining stress from the rubber tube) before the finial hydration stage leads to flux decrease if under a certain hydraulic gradient (i.e., permeability decreases). Results show that in the final hydration stage, permeability increases rapidly with decreasing suction, because large pore compacting is complete while saturation degree increases and bentonite swells to some extent. Results show that at the same suctions, the unsaturated permeabilities located at the sensor closest to the water injection device are the largest among the four sensors, which could be explained with “critical gradient” concept for unsaturated expansive clay or effect of hydraulic gradient from boundary water pressure.

A highly regio-specific and donor-promiscuous 3- O-glycosyltransferase, Sb3GT1 (UGT78B4), was discovered from Scutellaria baicalensis. Sb3GT1 could accept five sugar donors (UDP-Glc/-Gal/-GlcNAc/-Xyl/-Ara) to catalyze 3- O-glycosylation of 17 flavonols, and the conversion rates could be >98%. Five new glycosides were obtained by scaled-up enzymatic catalysis. Molecular modeling and site-directed mutagenesis revealed that G15 and P187 were critical catalytic residues for the donor promiscuity. Sb3GT1 could be a promising catalyst to increase structural diversity of flavonoid 3- O-glycosides.

Novel ring-opening reactions are achieved employing benzofuroxan as a new type of iminating or aminating reagent. These diverse transformations give access to three types of molecular scaffolds, N-aryl dimethylsulfoximines, methanesulfonamides, and hemiaminal ethers, which are important structural motifs in organic and medicinal chemistry. The procedures feature solvent-involved reactions, easily available starting materials, operational simplicity, high atom economy, and the potential further transformation of nitro group.

The terpene-conjugated curcuminoid bisabolocurcumin ether (BCE) is a newly identified bioactive curcuminoid, but its abundance in different Curcuma species is unknown. We developed an efficient MCI-gel-based method to purify BCE from C. longa, and established BCE fragmentation pathways under ESI-MS/MS. The abundances of BCE curcumin, demethoxycurcumin, and bisdemethoxycurcumin determined in C. longa rhizomes from Thailand, Indonesia, and China, C. longa roots from China, and C. phaeocaulis rhizomes from China. The abundance of the four compounds varied significantly, not only among different Curcuma species and cultivation regions, but also among different parts of the same species. BCEs were only detected in C. longa from Thailand and China, and in C. longa roots. C. longa from Thailand showed the highest abundance of curcuminoid [average 85.07 mg/g] and BCE [average 0.64 mg/g]. Moreover, BCE and three curcuminoids showed anti-inflammatory potential, as evidenced by the inhibition of lipopolysaccharide-induced production of nitric oxide in macrophages.

Angucyclinones are aromatic polyketides that possess impressive structural diversity and significant biological activities. The structural diversity of these natural products is attributed to various enzymatic or nonenzymatic modifications on their tetracyclic benz(a)anthracene skeleton. Previously, we discovered an unusual phenylamine-incorporated angucyclinone (1) from a marine Streptomyces sp. PKU-MA00218, and identified that it was produced from the nonenzymatic conversion of a C-ring-cleaved angucyclinone (2) with phenylamine. In this study, we tested the nonenzymatic conversion of 2 with more phenylamine analogues, to expand the utility of this feasible conversion in unusual angucyclinones generation. The (3-ethynyl)phenylamine and disubstituted analogues including (3,4-dimethyl)phenylamine, (3,4-methylenedioxy)phenylamine, and (4-bromo-3-methyl)phenylamine were used in the conversion of 2, which was isolated from the fermentation of Streptomyces sp. PKU-MA00218. All four phenylamine analogues were incorporated into 2 efficiently under mild conditions, generating new compounds 3–6. The activation of 3–6 on nuclear factor erythroid 2-related factor 2 (Nrf2) transcription were tested, which showed that 4 possessing a dimethyl-substitution gave most potent activity. These results evidenced that disubstitutions on phenylamine can be roughly tolerated in the nonenzymatic reactions with 2, suggesting extended applications of more disubstituted phenylamines incorporation to generate new bioactive angucyclinones in the future.

Consistency evaluation of Traditional Chinese Medicinal preparations (TCMPs) with complex chemical composition is challenging. Chaihuang granules (CHG), as a well-known TCMP, consists of Chaihu (Bupleuri Radix) and Huangqin (Scutellariae Radix) extract. In this work, we used pharmacokinetics and metabolomics to evaluate consistency of CHG products from two different manufacturers. In the pharmacokinetic study, a liquid chromatography tandem mass spectrometry (LC–MS/MS) method was applied to determine the plasma concentration-time profiles of baicalin in rat plasma. Pharmacokinetic parameters, including the maximum concentration in blood (Cmax), area under the curve (AUC), the time to reach Cmax (Tmax), and half-life (T1/2), were calculated to assess the consistency preliminarily. And there was no significant difference in these pharmacokinetic parameters between the two CHG. In LC–MS-based metabolomics, the metabolic response profiles changes based on relative distance values (RDV) to different CHG products were compared. Meanwhile, the kinetic process of 31 differential endogenous metabolites that altered by CHG were determined. Metabolomics data showed the similar metabolic regulation effects to rats of the two formulations. Both pharmacokinetic and metabolomics results indicated there was no significant difference between CHG products. Furthermore, metabolic pathways significantly altered by CHG were elucidated, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, and sphingolipid metabolism. Pharmacokinetics combined with metabolomics could provide a comprehensive perspective for consistency evaluation of CHG.

Developing a precise and reproducible bandgap tuning method that enables tailored design of materials is of crucial importance for optoelectronic devices. Towards this end, we report a sphere diameter engineering (SDE) technique to manipulate the bandgap of two-dimensional (2D) materials. A one-to-one correspondence with an ideal linear working curve is established between the bandgap of MoS2 and the sphere diameter in a continuous range as large as 360 meV. Fully uniform bandgap tuning of all the as-grown MoS2 crystals is realized due to the isotropic characteristic of the sphere. More intriguingly, both a decrease and an increase of the bandgap can be achieved by constructing a positive or negative curvature. By fusing individual spheres in the melted state, post-synthesis bandgap adjustment of the supported 2D materials can be realized. This SDE technique, showing good precision, uniformity and reproducibility with high efficiency, may further accelerate the potential applications of 2D materials. The bandgap of 2D molybdenum disulfide can be tuned uniformly, reproducibly and precisely over a large range by using a glass sphere support and changing the diameter of the spheres.

Acylated compounds are often present in herbal medicines. In this study, a diagnostic product ion-based strategy was established to comprehensively characterize acylated compounds in Scrophulariae Radix. After untargeted data acquisition using ultra-high performance liquid chromatography coupled with Orbitrap mass spectrometry, the data were processed by three-stage diagnostic product ions. First, diagnostic product ions corresponding to the acyl groups (cinnamoyl, p-coumaroyl, feruloyl, and caffeoyl) were used to search 90 compounds. Second, these compounds were divided into three categories using diagnostic product ions for phenylethanoid glycosides, iridoid glycosides, and phenylpropanoids, respectively. Last, the linkage position of the acyl group to iridoid glycosides was discriminated via the third-stage diagnostic product ions. As a result, 90 acylated compounds were characterized, and 37 of them were reported from Scrophulariae Radix for the first time.

Ligustri Lucidi Fructus (LLF) is a traditional Chinese medicine to treat osteopathic and hepatic diseases. Wine steaming is the major processing method for LLF in Chinese Pharmacopoeia, but the chemical changes involved are still unclear. In this study, a research strategy was proposed to reveal the chemical changes during wine steaming processing of LLF. Firstly, in total 104 compounds were tentatively identified using UHPLC/Orbitrap-MS. Secondly, potential chemical changes were revealed by comparing the peak areas of the 104 compounds between LLF and the corresponding wine-steamed LLF (WLLF). The results indicated that iridoid and phenylethanoid esters were readily hydrolyzed during wine steaming processing, while organic acids, flavonoids, and triterpenes were stable. Finally, 7 selected compounds were simultaneously determined in 21 batches of LLF/WLLF samples using a 10-min UPLC/UV method. The contents of 4 esters decreased from 3.64% to 2.71%, and the contents of 3 potential hydrolysis products increased from 0.27% to 0.88% after processing. Our study indicated that hydrolysis of iridoid and phenylethanoid esters such as specneuzhenide was responsible for the chemical changes during the wine processing of LLF. The proposed strategy could be employed to investigate the chemical changes of other herbs during processing.

Morphological change in retinal vessel diameters has been reported to be associated with negative cardiovascular outcomes, but its association with left ventricular diastolic dysfunction (LVDD) is not clear. This study aimed to examine the association between echocardiographic markers of LVDD and retinal vascular diameters, in untreated masked hypertension (MH). In this observational study, 105 MH patients without other cardiovascular risks were included (mean age 48.4 ± 5.7, female 72.4%). All individuals underwent extensive clinical and laboratory investigations, including echocardiography, ambulatory blood pressure monitoring, and retinal vascular diameters measured by optical coherence tomography. In the group, LVDD was diagnosed in 36 participants evaluated by left ventricular volume index, E/A and E/e' ratio. Compared to non-LVDD, LVDD subjects displayed narrower retinal arteriolar diameter (139.1 ± 33.8 vs 165.1 ± 29.1; adjusted P = .007) and wider retinal venular diameter (237.9 ± 42.2 vs 214.9 ± 44.8; adjusted P = .045). Significant and independent associations were demonstrated for retinal arteriolar narrowing and E/A ratio (adjusted β = 0.744, P = .031) and for retinal arteriolar diameter and E/e' ratio (adjusted β = -0.158, P = .001) after controlling for age, gender, body mass index, ambulatory systolic blood pressure, low-density lipoprotein cholesterol, and retinal venular diameter. In untreated MH subjects, retinal arteriolar diameter, a marker of microvascular damage, was independently associated with echocardiographic markers of diastolic dysfunction. These findings might underscore the hypothesis that microvascular disease could contribute to cardiac remodeling.

To study the role of Neural precursor cell expressed developmentally down-regulated protein 4.1 on ubiquitination of central Insulin-like growth factor 1β pathway in Alzheimer’s Disease, and to clarify the molecular mechanism of Neural precursor cell expressed developmentally down-regulated protein 4.1 and Insulin-like growth factor 1β for central insulin signalling pathway damage. Mouse hippocampal neurons cells were isolated from Intracerebral haemorrhage mice. 30 μM or 300 μM S-Nitroso-l-cysteine were incubated with hippocampal neurons cells for 4 h. pCMV-Neural precursor cell expressed developmentally down-regulated protein 4.1 or siR- Neural precursor cell expressed developmentally down-regulated protein 4.1 were synthesized and transfected into S-Nitroso-l-cysteine treated hippocampal neurons cells. Cycloheximide and MG132 were incubated with hippocampal neuron cells after S-Nitroso-l-cysteine stimulation. Insulin resistant brain state model were constructed by streptozotocin injection. Western blot were used to test the expression of neural precursor cell expressed developmentally down-regulated protein 4.1, Insulin-like growth factor-1Rβ, Protein kinase B and p- Protein kinase B, Glycogen synthase kinase 3β and p- Glycogen synthase kinase 3β, Tau protein and p-Tau protein in vitro and in vivo. Coimmunoprecipitation were used to analyse Neural precursor cell expressed developmentally downregulated protein 4.1 and Insulin-like growth factor-1Rβ. Neural precursor cell expressed developmentally down-regulated protein 4.1 in the hippocampus of Tg2576 mice increased significantly compared to the control mice (p

A direct and rapid method for the synthesis of α-iminonitriles achieved good to excellent yields. A novel intermolecular dehydration reaction between 2-aminopyridines and nitroalkenes is reported via a rare-earth-metal catalyst. The merits of this transformation include cyanide-free protocol, short reaction time, simple operation, water as the only byproduct, commercially available reagents, good functional group tolerance, etc. Moreover, nitroalkenes are demonstrated as a new "CN" source in this transformation.

Gibberellic acid (GA3) is an important phytohormone that is applied in agriculture, nurseries, tissue culture, tea gardens, etc. However, it has some drawbacks such as potential hazardous effects on mammals and labile in the condition of a weak base or acid. In this study, the enhanced stability and bioavailability of GA3 were achieved by forming the inclusion complexes of GA3 with cyclodextrins (β- or γ-CD) and its derivative (HP-β-CD). In the preliminary plant growth regulation assay, GA3/CDs displays superior bioactivity compared to pure GA3 to help with the early seedling growth of cucumber and mung bean and the root growth of cucumber and mung bean, respectively. The results showed that there was a certain relationship between the inclusion ability, stability and bioactivity. The inclusion stability constants of gibberellin clathrate are consistent with the order of stabilities of the inclusion complex. Among these complexes, GA3/HP-β-CD possess highest inclusion constant, and the binding ability of the HP-β-CD not only enhances the stability of gibberellic acid in the stability test but also plays a slow release role in the bioactivity assay. Therefore, the complex of GA3 may be used as a promising plant growth regulator.

This paper aims to investigate whether there is a relationship between left atrial diameter (LAD) and target organ damage (TOD) in patients with type 2 diabetes mellitus (DM). Two-hundred-and-eleven patients with type 2 DM were recruited. Data on left ventricular mass index (LVMI), diabetic retinopathy, carotid intima–media thickness/carotid plaque, micro-albuminuria, and serum creatinine levels were collected to determine whether TOD occurred in patients with type 2 DM. Age, body mass index, waist-hip ratio, a history of DM, Framingham Score, and 10-year risk were used to assess cardiovascular disease risk. Patients were divided into four groups: zero TOD (group I, n = 50), one TOD marker (group II, n = 76), two TOD markers (group III, n = 51), and at least three TOD markers (group IV, n = 34). Using multivariate regression analyses, age, body mass index, waist-hip ratio, a history of DM, Framingham Score, and 10-year risk were significantly associated with LAD. LAD was associated with an increased number of markers for TOD. Univariate analyses demonstrated significant relationships between LAD and TOD in the context of serum creatinine and urinary albumin creatinine ratio (r = 0.292, p