Search

An organic-inorganic hybrid polyiodate, namely, [o-C5 H4 NHOH]2 [I7 O18 (OH)]⋅3 H2 O (I), featuring a novel branched polyiodate chain has been obtained by evaporation method. [o-C5 H4 NHOH]2 [I7 O18 (OH)]⋅3 H2 O (I) crystalizes in the polar space group Ia and features an [I7 O18 (OH)] ∞2- branched polyiodate chain in which [I3 O9 ]3- trimers are grafted on the same side of the one-dimensional (1D) chain based on [I4 O11 (OH)]3- tetramers. The asymmetric organic amine groups are beneficial to the polymerization of iodate groups and inducing the formation of the non-centrosymmetric (NCS) structure. Compound I exhibits a rather large Second-Harmonic- Generation (SHG) signal of 8.5×KH2 PO4 (KDP) upon 1064 nm laser radiation, a moderate band gap of 3.90 eV and a high laser-induced-damage-threshold (LIDT) of 182.34 MW cm-2 , hence it is a promising new SHG material. The relationship between the structures of the organic amine groups and the overall structures has been also analyzed.

Aims Despite considerable therapeutic advances, there is still a dearth of evidence on the molecular determinants of cardiac hypertrophy that culminate in heart failure. Neuraminidases are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids. This study sought to characterize the role of neuraminidases in pathological cardiac hypertrophy and identify pharmacological inhibitors targeting mammalian neuraminidases. Methods and results Neuraminidase 1 (NEU1) was highly expressed in hypertrophic hearts of mice and rats, and this elevation was confirmed in patients with hypertrophic cardiomyopathy (n = 7) compared with healthy controls (n = 7). The increased NEU1 was mainly localized in cardiomyocytes by co-localization with cardiac troponin T. Cardiomyocyte-specific NEU1 deficiency alleviated hypertrophic phenotypes in response to transverse aortic constriction or isoproterenol hydrochloride infusion, while NEU1 overexpression exacerbated the development of cardiac hypertrophy. Mechanistically, co-immunoprecipitation coupled with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated that NEU1 translocated into the nucleus and interacted with GATA4, leading to Foetal gene (Nppa and Nppb) expression. Virtual screening and experimental validation identified a novel compound C-09 from millions of compounds that showed favourable binding affinity to human NEU1 (KD = 0.38 μM) and effectively prevented the development of cardiac remodelling in cellular and animal models. Interestingly, anti-influenza drugs zanamivir and oseltamivir effectively inhibited mammalian NEU1 and showed new indications of cardio-protection. Conclusions This work identifies NEU1 as a critical driver of cardiac hypertrophy and inhibition of NEU1 opens up an entirely new field of treatment for cardiovascular diseases.

Monodispersed palladium phosphide (Pd3P) (5.2 ± 0.5 nm) was firstly applied to photocatalytic Suzuki coupling reaction under visible light irradiation with CdS nanoflake as a photosensitizer. This heterogeneous system exhibited high yields to corresponding products and excellent stability in alcohol solvent at room temperature.

The ternary strategy is promising to enhance the photovoltaic properties of organic solar cells (OSCs). Nevertheless, it is full of challenges when this approach involves only small molecules. Herein, a fullerene derivative, ICBA is introduced as the third component to improve the photovoltaic performance of BTR-Cl:Y6-based all-small-molecule (ASM) OSCs. The significant performance enhancement mainly results from reduced bimolecular and trap-assistant recombination, prolonged carrier lifetime and facilitated charge extraction. These findings highlight the effectiveness of the ternary strategy and pave an alternative way for third component selection.

A continuous-flow photocatalytic synthesis of the industrially important thiuram disulfides has been developed, utilizing O2 as the oxidant and Eosin Y as the photoredox catalyst. This highly atom- and step-economical method features much reduced reaction time as well as excellent product yield and purity, making it a sustainable and potentially scalable process for industrial production.

Selenophene substitution of photovoltaics materials can improve their intermolecular interactions and thus offer a good opportunity to finely optimize their phase separation morphology to an ideal state. However, the performance of this substitution strategy is yet unclear in liquid crystalline donors, which have demonstrated high efficiency. The combination of those structural advantages may help to achieve state-of-the-art device performance. Herein, two new liquid crystalline small molecule donors are designed and synthesized with different substituents on benzo[1,2-b:4,5-b′]dithiophene (BDT) central units, including L1 with thiophene group and L2 with selenophene group, for investigating the effect of selenophene substitution on morphology and photovoltaic performance of liquid crystalline donors. Unlike the control donor L1, the selenide donor L2 shows a higher intramolecular interaction and presents a novel sematic liquid crystal phase, which results in a more favored morphology, better light harvest, and lower charge recombination. As a result, outstanding power conversion efficiency up to 15.8% is realized in the L2:Y6 based devices. Particularly promising is the fact that selenide-based devices with active layer thicknesses up to ∼300 nm can still output a high PCE of 14.3%, which is promising for roll-to-roll printing processes with large-scale production. To our best knowledge, the PCEs of 15.8% and 14.3% are the highest values reported to date in binary ASM-OSCs and thick-film ASM-OSCs, respectively. These excellent values demonstrated the superiority of selenophene in the construction of efficient small molecule liquid crystalline donors.

Random ternary copolymerization is a simple but effective strategy to develop new efficient polymer donors for polymer solar cell application. Herein, a series of new copolymers, OPz1, OPz2, OPz3, ...

To meet device applications, it is essential to fabricate nondegenerate ZnSnN2 with higher mobility. Herein, the chemical potential of nitrogen was improved under Zn-rich sputtering conditions and nondegenerate ZnSnN2 with mobility higher than 20 cm2 V−1 s−1 was successfully fabricated. The properties of the samples were characterized. The obtained ZnSnN2 is wurstite. Band conduction is observed in the range 300–100 K and nearest neighbour hopping is observed in the range 100–70 K. The forbidden band gap is about 1.43 eV and Sn substituting Zn is the major donor, whose ionization energy is 34.6 meV. Improving the chemical potential of nitrogen under Zn-rich conditions effectively changes the off-stoichiometry of ZnSnN2 and unintentionally increases oxygen doping, which finally leads to a decrease in electron density and an increase in mobility.

The combination of d0 transition metal oxofluorides with iodate anions helps to synthesize polar crystals. Herein, a novel polar crystal, K3V2O3F4(IO3)3, which is the first metal vanadium iodate with two types of V5+-centered polyhedra (VO4F2 octahedron and VO3F2 trigonal bipyramid), has been prepared hydrothermally. It crystallizes in the polar space group of Cmc21 and its structure displays an unprecedented 0D [V2O3F4(IO3)3]3− anion, which is composed of Λ-shaped cis-[VO2F2(IO3)2]3− and [VO2F2(IO3)]2− anions interconnected via the corner-sharing of one oxo anion. The synergy gained from the VO4F2, VO3F2 and IO3 groups resulted in K3V2O3F4(IO3)3 exhibiting both a strong second-harmonic generation (SHG) response (1.3 × KTiOPO4) under 2050 nm laser irradiation and a large birefringence (0.158 @ 2050 nm). This study provides a facile route for designing SHG materials by assembling various vanadium oxide-fluoride motifs and iodate anions into one compound., K3V2O3F4(IO3)3, which is the first metal vanadium iodate containing two different V-centered polyhedra, exhibits a strong SHG effect of 1.3 × KTP and a large birefringence of 0.158 @ 2050 nm.

Objective To determine the safety and effectiveness of a cross-linked sodium hyaluronate (CHA) scaffold in cartilage repair. Methods Physicochemical properties of the scaffold were determined. The safety and effectiveness of the scaffold for cartilage repair were evaluated in a minipig model of a full-thickness cartilage defect with microfracture surgery. Postoperative observation and hematological examination were used to evaluate the safety of the CHA scaffold implantation. Pathological examination as well as biomechanical testing, including Young's modulus, stress relaxation time, and creep time, were conducted at 6 and 12 months postsurgery to assess the effectiveness of the scaffold for cartilage repair. Furthermore, type II collagen and glycosaminoglycan content were determined to confirm the influence of the scaffold in the damaged cartilage tissue. Results The results showed that the routine hematological indexes of the experimental animals were within the normal physiological ranges, which confirmed the safety of CHA scaffold implantation. Based on macroscopic observation, it was evident that repair of the defective cartilage in the animal knee joint began during the 6 months postoperation and was gradually enhanced from the central to the surrounding region. The repair smoothness and color of the 12-month cartilage samples from the operation area were better than those of the 6-month samples, and the results for the CHA scaffold implantation group were better than the control group. Greater cell degeneration and degeneration of the adjacent cartilage was found in the implantation group compared with the control group at both 6 and 12 months postoperation, evaluated by O'Driscoll Articular Cartilage Histology Scoring. Implantation with the CHA scaffold matrix promoted cartilage repair and improved its compression capacity. The type II collagen level in the CHA scaffold implantation group tended to be higher than that in the control group at 6 months (2.33 ± 1.50 vs 1.68 ± 0.56) and 12 months postsurgery (3.37 ± 1.70 vs 2.06 ± 0.63). The GAG content in the cartilage of the control group was significantly lower than that of the experimental group (2.17 ± 0.43 vs 3.64 ± 1.17, P = 0.002 at 6 months and 2.27 ± 0.38 vs 4.12 ± 1.02, P = 0.002 at 12 months). Type II collagen and glycosaminoglycan content also demonstrated that CHA was beneficial for the accumulation of both these vital substances in the cartilage tissue. Conclusions The CHA scaffold displayed the ability to promote cartilage repair when applied in microfracture surgery, which makes it a promising material for application in the area of cartilage tissue engineering.

BACKGROUND The treatment of inflammatory bowel disease (IBD) is still not satisfactory and novel technologies are clinically needed. This study aimed to examine the effect of mesenchymal stromal cells (MSCs) coated with the anti-vascular cell adhesion molecule 1 (VCAM 1) antibody on experimental colitis. MATERIAL AND METHODS The antibody was coated onto the MSCs isolated from male BALB/C mice to generate anti-VCAM 1 antibody-coated MSC (V-MSC). The Transwell assay was used to detect migration rate. 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to generate experimental colitis. MSCs were injected intravenously into experimental models. Weight changes, disease activity index, and histological changes were evaluated. The SRY gene were used for cell tracking. Expression of Ki67 and claudin 1 was used to measure local repair using immunohistochemistry. T helper (Th)1, Th2, Th17, and T regulatory cells were counted. RESULTS V-MSCs were successfully generated through coating MSCs with VCAM1 antibody. Analysis showed that the V-MSCs had similar surface types and differentiation as uncoated MSCs. Transwell assays showed that V-MSCs had higher migration rate than MSCs. After injection of V-MSCs, the expression of the SRY gene was enhanced in diseased colon and all indices (including weight changes, DAI score, histological changes, and the expressions of Ki67 and claudin 1) recovered rapidly. The ratio of proinflammatory Th1 and Th17 cells decreased, but the ratio of anti-inflammatory Th2 and Treg cells increased after the treatment. CONCLUSIONS V-MSCs enhance homing and modulating immune balance in the experimental colitis, suggesting that they are potentially useful for treating inflammatory bowel disease or other immune diseases.

A palladium-catalyzed enantioselective intramolecular σ-bond cross-exchange between C-I and C-C bonds is realized, providing chiral indanones bearing an alkyl iodide group and an all-carbon quaternary stereocenter. Pd/TADDOL-derived phosphoramidite is found to be an efficient catalytic system for both C-C bond cleavage and alkyl iodide reductive elimination. In addition to aryl iodides, aryl bromides can also be used for this transformation in the presence of KI. Density-functional theory (DFT) calculation studies support the ring-opening of cyclobutanones occuring through an oxidative addition/reductive elimination process involving PdIV species.

The short- and long-term influence of quinoline on the properties of anaerobic ammonium oxidation (anammox) biogranules was evaluated. During batch tests, the bioactivity of anammox granules in the presence of different quinoline concentrations was monitored, and the IC50 of quinoline was calculated to be 13.1 mg L−1 using a non-competitive inhibition model. The response of anammox granules to pre-exposure to quinoline was dependent on metabolic status, and the presence of both quinoline and NO2−-N had a rapid detrimental effect, resulting in a 64.5% decrease within 12 h. During continuous-flow experiments, the nitrogen removal rate (NRR) of the reactor decreased sharply within 3 days in the presence of 10 mg L−1 quinoline and then was restored to 2.6 kg N m−3 d−1. In the presence of quinoline-induced stress, the specific anammox activity and levels of extracellular polymeric substance and heme c were decreased, while settling velocity persistently increased. After cultivation and acclimation obtained by adding a medium level of quinoline to the influent, the anammox granule sludge was able to tolerate 10 mg L−1 quinoline in 178 days.

The Isodon plants (Lamiaceae) have been used in traditional Chinese medicine to alleviate sufferings from inflammations and cancers. This feature has been attributed to the presence of pharmacologically active ent-kaurane diterpenoids such as eriocalyxin B and oridonin. The Isodon eriocalyx (Dunn) Kudô species native to southwest China can accumulate a particularly high content of ent-kaurane diterpenoids (∼1.5% w/w of dried leaves). We previously identified diterpene synthases IeCPS1 and IeCPS2 as ent-copalyl diphosphate synthases (ent-CPS) potentially involved in Isodon ent-kaurane diterpenoids biosynthesis. In this study, analysis of RNA-seq transcriptome of the I. eriocalyx plant revealed three other diterpene synthase genes (IeCPS3, IeKS1, and IeKSL1). Their functional characterization through coupled in vitro enzyme assays has confirmed that IeCPS3 is an ent-CPS specifically producing ent-copalyl diphosphate (ent-CPP). IeKS1 accepted ent-CPP to produce exclusively ent-kaurene and may thus be defined as an ent-kaurene synthase (ent-KS). When IeKSL1 was combined with IeCPS2 or IeCPS3, no product was detected. Based on tissue-specific expression and metabolic localization studies, the IeCPS3 and IeKS1 transcripts were significantly accumulated in leaves where the ent-kaurane diterpenoid eriocalyxin B dominates, whereas weak expression of both were observed in germinating seeds in which gibberellin biosynthetic pathway is normally active. Our findings suggest that both IeCPS3 and IeKS1 possess dual roles in general (gibberellins) and specialized diterpenoid metabolism, such as that of the Isodon ent-kaurane diterpenoids.

Optimization of metal–support interactions (MSIs) is at the core of heterogeneous catalyst design. For polar reactants, electrostatic interactions resulting from MSIs can facilitate their activation. In this work, a feasible in situ method has been employed to control the electrostatic properties at the interface of a noble-metal-free Cu/Co(OH)2 nanohybrid catalyst. On the Cu/Co(OH)2 interface, the positively charged copper enhances the polar molecule adsorption. By varying the metal/support ratio, a highly efficient catalytic activity for the methanolysis of ammonia borane (AB) with an initial turnover frequency (TOF) of 61.63 mol(H2) mol(catalyst)−1 min−1 and long-term stability at ambient temperature were observed. Theoretical analysis unravels the role of charge transfer in promoting the reactions and the metal/support ratio in manipulating the catalytic activity via tuning electrostatic interactions.

A new protocol for Pd(OAc)2-catalyzed reactions of different benzyl bromides and various arylboronic acids has been developed to form functionalized benzyl phenyl ethers. This method represents the first instance where arylboronic acid is used as a reaction substrate for benzyl phenyl ether synthesis with H2O2 as the green oxidant under atmospheric oxygen and pure H2O as an environmental friendly solvent without the requirement for phosphine- and N-based ligands, remarkable functional group tolerance, and considerable yield.

The development of an effective and safe hydrogen evolution catalytic system depends on the advent of a well-established hydrogen-economy paradigm in the future. Catalytic hydrogen generation from promising hydrogen storage materials, such as ammonia-borane (AB), has drawn extensive attention in recent years. However, the wide use of noble metal catalysts in the catalytic hydrogen generation from AB is one of the formidable challenges in the practical application of this strategy on a large scale. Herein, using a bimetallic metal–organic framework (MOF) template strategy, we successfully engineered three-dimensional (3D) porous cobalt phosphide carbon-based nanoframeworks (CoP@CNFs) as precious metal-free and efficient catalysts. Zn present in the MOF precursor plays the dual crucial role of separating the Co ions and maintaining the framework during pyrolysis. As a result, the porous CoP@CNF exhibits large specific surface area, a hierarchical porous structure, well-exposed active sites and hydrophilic channels, yielding the extraordinary initial total turnover frequency (TOF) of 165.5 mol(H2) mol(Co)−1 min−1 for hydrogen generation from AB.

Herein, we first describe the physical mixture of Cu(OH)2/Fe(OH)3 as a composite catalyst precursor for the dehydrogenation of ammonia borane (AB) in methanol. During the initial period of catalytic reaction, Cu nanoparticles were formed in-situ. The catalytic activity of Cu nanoparticles can be significantly enhanced with the assistance of Fe species and OH−. A maximum turnover frequency (TOF) of 50.3 molH2 moltotal metal−1 min−1 (135.6 molH2 molCu−1 min−1) was achieved at ambient temperature, which is superior to those of previously reported Fe or Cu based systems.

Neuraminidase, also known as sialidase, is ubiquitous in animals and microorganisms. It is predominantly distributed in the cell membrane, cytoplasmic vesicles, and lysosomes. Neuraminidase generally recognizes the sialic acid glycosidic bonds at the ends of glycoproteins or glycolipids and enzymatically removes sialic acid. There are four types of neuraminidases, named as Neu1, Neu2, Neu3, and Neu4. Among them, Neu1 is the most abundant in mammals. Recent studies have revealed the involvement of Neu1 in several diseases, including cardiovascular diseases, diabetes, cancers, and neurological disorders. In this review, we center the attention to the role of Neu1 in cardiovascular diseases, including atherosclerosis, ischemic myocardial injury, cerebrovascular disease, congenital heart disease, and pulmonary embolism. We also summarize inhibitors from Chinese herbal medicines (CHMs) in inhibiting virus neuraminidase or human Neu1. Many Chinese herbs and Chinese herb preparations, such as Lonicerae Japonicae Flos, Scutellariae Radix, Yupingfeng San, and Huanglian Jiedu Decoction, have neuraminidase inhibitory activity. We hope to highlight the emerging role of Neu1 in humans and potentially titillate interest for further studies in this area.

Evidence shows that long noncoding RNAs (lncRNAs) modulate mRNAs of multiple genes by post-transcriptional regulation. However, in esophageal squamous cell carcinoma, lncRNAs involvement in post-transcriptional regulation of mRNAs have been rarely reported. In this study, we investigated a novel mechanism of linc01305 promoting metastasis and proliferation of ESCC. The results for real-time quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization showed that linc01305 was highly expressed and predominantly located in cytoplasm of human esophageal cancer cells. Transwell and colony formation assays confirmed that linc01305 promoted migration and proliferation of esophageal cancer cells. RNA-seq, linc01305 pulldown, mass spectrometry, RNA immunoprecipitation and mRNA stability assays demonstrated that linc01305 stabilized mRNA of target gene HTR3A through interacting with IGF2BP2 and IGF2BP3. Taken together, our data unveils a novel mechanism in which cytoplasmic linc01305 stabilizes HTR3A mRNA through interacting with IGF2BP2 and IGF2BP3 and thereby promotes metastasis and proliferation of ESCC.

Ethnopharmacological relevance As a classic herbal prescription, Huanglian Jiedu Decoction (HLJDD) exhibits positive effects against cardiac dysfunction. However, its cardioprotective effects and potential mechanism(s) of action still need to be systematically investigated. Aim of the study This study aimed to reveal the underlying therapeutic mechanism of HLJDD on transverse aortic constriction (TAC)-induced pathological cardiac hypertrophy and remodeling. Materials and methods TAC-induced cardiac hypertrophy and remodeling mice model was established to evaluate the therapeutic effects of HLJDD. Serum untargeted metabolomics and lipidomic profiling were performed using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry coupled with multivariate statistical analyses. Results Oral administration of HLJDD (2.5 g/kg/day, 5.0 g/kg/day) significantly improved the heart morphology, enhanced the heart function, and alleviated the accumulation of fibrosis in the interstitial space and the infiltration of inflammatory cells in TAC-stimulated mice. Serum untargeted metabolomics analysis showed that significant alterations were observed in metabolic signatures between the TAC-model and sham group. Principal component analysis and orthogonal partial least-squares discriminant analysis screened 59 differential metabolic features and 13 metabolites were identified. The disturbed metabolic pathways in TAC group mainly related to lipid metabolism. Further serum lipidomic profiling showed that most lipids including cholesterol esters, ceramides, glycerides, fatty acids and phospholipids were decreased in TAC group and these alterations were reversed after HLJDD intervention. Conclusion HLJDD alleviates TAC-induced pathological cardiac hypertrophy and remodeling, and its potential therapeutic mechanism involves the regulation of lipid metabolism.

Two different terminal groups, rhodanine-flanked benzo[c][1,2,5]thiadiazole (BR) and 2-(5,6-difluoro-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (IM2F), were connected to an indaceno[1,2-b:5,6-b′]dithiophene (IDT) core to construct a new non-fullerene acceptor (IDTBF). Solar cells based on this acceptor exhibited promising photovoltaic performances with a power conversion efficiency (PCE) of up to 10.43%.

Herein, we reported two alkali metal molybdenum(VI) iodates, namely, NaMoO3(IO3) and γ-KMoO3(IO3) with 1D and 3D [MoO3(IO3)]− anionic architectures, respectively. The novel 1D chain in NaMoO3(IO3) and the 3D network in γ-KMoO3(IO3) are constructed by the 0D Λ-shaped cis-[MoO4(IO3)2]4− building units interconnected by bridging IO3− anions as well as the corner-sharing of oxo anions. Importantly, the polar γ-KMoO3(IO3) exhibits a very large second-harmonic generation (SHG) effect of 12 × KH2PO4 (KDP) under 1064 nm laser radiation, a high laser-Induced damage threshold value (52 × AgGaS2), and a moderate birefringence of 0.087@1064 nm, whereas the centrosymmetric NaMoO3(IO3) has a large birefringence of 0.208@1064 nm. This study further proves the useful route of exploring promising optical materials via assembling the 0D basic building units into higher dimensional anionic architectures.

Three tungsten oxides (WO3-W1 to WO3-W3) with different morphologies were prepared and characterized by XRD, SEM, TEM and HR-TEM measurements. The as-synthesized tungsten oxides were screened as photocatalysts for visible-light-driven cross dehydrogenative coupling (CDC) reactions along with commercially available WO3-W4. Preliminary studies showed that WO3-W1 with hollow sphere morphology efficiently photocatalyzed oxidative C H functionalization as compared to other tested samples, by using molecular oxygen as a benign oxidant. The superior photocatalytic performance of WO3-W1 can be attributed to its larger surface area and pore structure which was supported by nitrogen adsorption-desorption measurements. Further, this protocol was used to synthesize α-functionalized tertiary amines in good to excellent yields by irradiating a mixture of WO3-W1, tertiary amine, and nucleophiles (nitromethane or ketones) to visible light under aerobic conditions. Moreover, WO3-W1 can be recycled and reused with no obvious change in catalytic activity, indicating that this is an environmentally friendly and economical protocol and also underlines the robustness of the catalysts in light mediated cross dehydrogenative coupling reactions. It is hoped that our results could offer useful information for designing of new heterogeneous semiconductors for photoredox catalytic organic reactions.

NiFe-layered double hydroxide (NiFe LDH) is a state-of-the-art oxygen evolution reaction (OER) electrocatalyst, yet it suffers from rather poor catalytic activity for the hydrogen evolution reaction (HER) due to its extremely sluggish water dissociation kinetics, severely restricting its application in overall water splitting. Herein, we report a novel strategy to expedite the HER kinetics of NiFe LDH by an Ir4+-doping strategy to accelerate the water dissociation process (Volmer step), and thus this catalyst exhibits superior and robust catalytic activity for finally oriented overall water splitting in 1 M KOH requiring only a low initial voltage of 1.41 V delivering at 20 mA cm−2 for more than 50 h.

Three Strandberg-type polyoxometalate compounds [Cu(L)2(H2O)2]2H2[P2Mo5O23]·2CH3OH (1), [Cu(L)2(H2O)]H2[Cu(L)2(P2Mo5O23)]·4H2O (2), [Cd(L)2(H2O)2]2H2[P2Mo5O23]·2CH3OH (3), (L = pyridine-2-carboxamide) have been synthesized and structurally characterized by elemental analysis, spectroscopic methods (IR and UV–vis) as well as single crystal X-ray diffraction. Single-crystal X-ray structural analyses indicate that 1 and 3 are isostructural and crystallized in monoclinic, space group I2/a. Biological studies have indicated that compounds 1–3 exhibit broad and effective activities against the tested cells. A synergistic effect involving L, metal and P2Mo5 could probably explain the improved growth-inhibiting properties. Both coordination mode and the type of metal ion play significant roles in these compounds cytotoxicity.

One novel coordination polymer (CP) and one new supramolecular compound based on an unsymmetrical tetracarboxylate, namely, [Cu2(bptc) (bpy)2]·2H2O (H4bptc ​= ​2,3,3′,4′-biphenyl tetracarboxylic acid; bpy ​= ​2,2′-bipyridine) 1, [Ni(phen)3](H3bptc)2 (phen ​= ​1,10-phenanthroline) 2 have been solvothermally synthesized. Single-crystal X-ray diffraction analysis indicates that CP 1 displays a 1-D chain structure, which self-assembles into a final 3-D supramolecular network via the interchain π⋯π interactions. Supramolecular compound 2 is a phen-propagated mononuclear Ni(II) complex with H3bptc− as the templating agent. Notablely, the H4bptc molecules are uncoordinated and only act as the guest molecules. Luminescence investigations indicate that compound 2 can sensitively and selectively detect acetylacetone (acac) with high KSV value of 9.67 ​× ​104 ​M−1 and low limit of detection (LOD) of 18.9 ​ppb. In addition, the probable quenching mechanisms are also investigated.

AIM To investigate whether mesenchymal stem cells (MSCs) from adipose-derived stromal cells (ADSCs) and bone marrow stromal cells (BMSCs) have similar hepatic differentiation potential. METHODS Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocyte-like cells. CM-Dil-labeled ADSCs and BMSCs were then transplanted into a mouse model of CCl4-induced acute liver failure. Fluorescence microscopy was used to track the transplanted MSCs. Liver function was tested by an automatic biochemistry analyzer, and liver tissue histology was observed by hematoxylin and eosin (HE) staining. RESULTS ADSCs and BMSCs shared a similar morphology and multiple differentiation capacity, as well as a similar phenotype (with expression of CD29 and CD90 and no expression of CD11b or CD45). Morphologically, ADSCs and BMSCs became round and epithelioid following hepatic induction. These two cell types differentiated into hepatocyte-like cells with similar expression of albumin, cytokeratin 18, cytokeratin 19, alpha fetoprotein, and cytochrome P450. Fluorescence microscopy revealed that both ADSCs and BMSCs were observed in the mouse liver at different time points. Compared to the control group, both the function of the injured livers and HE staining showed significant improvement in the ADSC- and BMSC-transplanted mice. There was no significant difference between the two MSC groups. CONCLUSION ADSCs share a similar hepatic differentiation capacity and therapeutic effect with BMSCs in an acute liver failure model. ADSCs may represent an ideal seed cell type for cell transplantation or a bio-artificial liver support system.

The short- and long-term effects of Mn2+ on the performance of anaerobic ammonium oxidation (anammox) granules were investigated in the present study. Anammox activity was determined at various Mn2+ concentrations in batch assays, and the 50% inhibition concentration value was determined to be 7.33 mg L−1. However, no obvious deterioration of reactor performance was observed during the 150-day continuous-flow operation, and the nitrogen removal efficiency of the test reactor (R1) fluctuated between 91% and 92% as the Mn2+ concentration was increased from 1 to 200 mg L−1. Additionally, the specific anammox activity, heme c content and the amounts of extracellular polymeric substances in the anammox biomass increased and then subsequently decreased. The results demonstrated that short-term exposure to Mn2+ has a negative effect on anammox biomass, but the biomass could tolerate Mn2+ stress after acclimation to a high concentration of 200 mg L−1 at the end of the continuous-flow experiment.

The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson’s disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner’s and Auerbach’s plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, α-syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α-Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.

The broad-spectrum antibiotic sulfamethoxazole (SMX) was chosen to assess its short- and long-term effects on denitrifying granules. The SMX concentration and pre-exposure time in batch testing influenced the denitrifying granule activity. In the continuous-flow experiments, no inhibitory effects on the upflow anaerobic sludge blanket performance were observed at SMX concentrations up to 100 mg L−1, probably because of functional redundancy and long-term acclimation. The specific denitrifying activity first decreased to a minimum of 49.3% and then recovered to a level comparable to the initial level as the SMX concentration increased. The changing trend of the extracellular polymer content was consistent with the specific denitrifying activity throughout the process, and relatively high EPS loss ratios (maximum loss of 61.8%) were observed. Additionally, the diameter of the denitrifying granules monophonically increased to a final value of 35.0%. This research provided the application of denitrifying granules to treat wastewater that contained antibiotic.

The robustness of an anaerobic ammonium oxidation (anammox) process under individual and combined thiocyanate (SCN−) and hydraulic shocks was investigated. The nitrogen removal performance and stability of a process subjected to transient SCN− (300, 600 and 900 mg L−1), hydraulic shock (2-fold increase in flow rate) and the combined effects of SCN− and hydraulic shock were evaluated. The sensitivity index (SI) was used to characterize the impact of the SCN−, and the SI exhibited a rising trend with increases in shock strength. The higher SI of effluent was reached after exposure to SCN− shocks (900 mg L−1) for 3 h, and the reactor performance was stable at a relatively lower SCN− concentration (300 mg L−1) after exposure to SCN− shocks for 1.5 and 3 h. The shock effect was mainly related to the SCN− concentration rather than the shock time. The similar phenomenon also was found in the test of combined SCN− and hydraulic shocks. The reactor performance in hydraulic shock tests was robust, and the relative low SAA loss ratios (9.2% and 4.0%) were observed. The specific anammox activity and heme c in the shock period were adversely affected, with maximum loss rates of 42.6% and 22.7%, respectively. However, the extracellular polymeric substance content during the shock period increased in varying degrees and antagonized exogenous disturbances. The results for these different shocks suggested that instabilities in the anammox process were dependent on both time and the concentration intensity.

The development of high-efficiency and low-cost catalysts for hydrogen release from chemical hydrogen-storage materials is essential for the hydrogen-economy paradigm. Herein, we report a facile and controllable method to fabricate a series of Co-doped nickel phosphides and their corresponding nanohybrids with graphene oxide (GO) as highly efficient, robust and noble-metal-free catalysts for ammonia borane hydrolysis. The incorporation of Co into Ni2P effectively optimizes the electronic structures of Ni2−xCoxP catalysts to enhance their interaction with AB and simultaneously facilitate the hydroxyl activation of AB, resulting in the reduction of the reaction energy barrier and thus substantial improvement of the catalytic rate.

In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol (RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrations. Cellular nucleoside metabolic profiling was determined by an established liquid chromatography-mass spectrometry method in A549 cells. RSV resulted in significant decreases and imbalances of deoxyribonucleoside triphosphates (dNTPs) pools suppressing subsequent DNA synthesis. Meanwhile, RSV at high concentration caused significant cell cycle arrest at S phase, in which cells required the highest dNTPs supply than other phases for DNA replication. The inhibition of DNA synthesis thus blocked subsequent progression through S phase in A549 cells, which may partly contribute to the cytotoxicity effect of RSV. However, hydroxyurea (HU), an inhibitor of RNR activity, caused similar dNTPs perturbation but no S phase arrest, finally no cytotoxicity effect. Therefore, we believed that the dual effect of high concentration RSV, including S phase arrest and DNA synthesis inhibition, was required for its cytotoxicity effect on A549 cells. In summary, our results provided important clues to the molecular basis for the anticancer effect of RSV on epithelial cells.

Lipopolysaccharide stimulates the intestinal microbiome to activate phosphoinositide 3 kinase (PI3K) signaling via several pathways; however, the direct effect that PI3K has on the intestinal bacterial community remains unclear. Herein, we investigate changes in the colonic microbiome of colitis PI3Kγ-knockout (PI3Kγ-/-) mice. Additionally, the effect of anal administration of colonic irrigation fluid from control mice to those with colitis was examined. Microbial 16S rRNA genes from the colonic mucosa of PI3Kγ-/- and WT mice were sequenced using Illumina MiSeq platform, and colonic IgA, IL-2, IL-10, and IL-17A production was quantified by western blot analysis. Myeloperoxidase (MPO) activity was detected by absorbance via colorimetric analysis. From the results, two new indices were derived by dividing the bacterial community into invading taxa, common taxa, and vanishing taxa. These indices were used to estimate the degree of microbiome disorder in chronic experimental colitis models. PI3Kγ-/- mice showed slower remission of inflammation as assessed by the disease activity index，pathological score, IL-2, IL-17, IL-10, IgA expression and MPO activity. The unique and common taxa of wild-type and PI3Kγ-/- mice increased as colitis symptoms regressed. Continuous loss of commensal bacteria happened with the continuous invasion of exogenous bacteria in the intestinal mucosa of PI3Kγ--/- mice after colitis begin to aggravate. However, transplantation of normal intestinal microbiota to PI3Kγ-/- mice promoted remission of inflammation; while the microbial dysbiosis observed during PI3Kγ dysfunction aggravated the intestinal microbiome disorder and impeded colitis recovery. Thus, the PI3Kγ signaling pathway may regulate microbial community composition in the colon.

Two novel complexes based on an unsymmetrical tetracarboxylate, namely, [Cd2(bptc)(bpp)(H2O)2]n·nH2O (1, H4bptc ​= ​2,3,3′,4′-biphenyl tetracarboxylic acid; bpp ​= ​1,3-bis(4-pyridyl) propane), [Cu(H2bptc)(phen)] (2, phen ​= ​1,10-phenanthroline) have been solvothermally synthesized with the aid of N-donor ligands. The structures, CHN analysis, IR analysis, thermal stabilities and photoluminescence properties of title complexes were investigated. Single-crystal X-ray diffraction analysis indicates that complex 1 demonstrates a novel 3-D network with (4, 5, 5) -connected (3ˑ4ˑ5ˑ6ˑ82) (3ˑ42ˑ5ˑ63ˑ83) (3ˑ43ˑ52ˑ63ˑ7) topology. Whereas complex 2 only possesses a mononuclear structure. Photoluminescence studies indicate that complex 1 shows a strong green light emission, while 2 exhibits blue emissions. Moreover, the luminescence properties of 2 can be utilized to sensitively and selectively detect acetylacetone in aqueous solution with the detection limit of 61.3 ​ppb. In addition, the probable mechanisms are also detailedly investigated, which indicate that the static photo-competitive absorption, photoinduced electron transfer and H-bonding interaction between sensor and analyte may be the main reasons for the fluorescence quenching effect.

Summary For the RNA world hypothesis, the direct condensation between nucleobase and ribose to afford canonical nucleoside has been a formidable challenge in terms of regioselectivity. In this report, we demonstrate that cavitation, a frequently occurring energy-intensive phenomenon upon the collapse of bubbles, could be a plausible driving force to form the purine nucleosides directly from nucleobase and ribose with the desired regioselectivity. Under cavitation, the overall yield of N9 nucleosides increases compared with non-cavitation conditions, whereas the amount of the undesired ribosylamino isomers decreases. Plausible geochemical scenarios on primordial Earth are proposed that could facilitate enrichment of the desired N9 nucleosides. Under salt-free dry-wet conditions, much improved yield (7.2%) and selectivity (N9/ribosylamino = 0.45) of the N9 isomers are achieved compared with the classical routes.

Single junction binary all‐small‐molecule (ASM) organic solar cells (OSCs) with power conversion efficiency (PCE) beyond 14% are achieved by using non‐fullerene acceptor Y6 as the electron acceptor, but still lag behind that of polymer OSCs. Herein, an asymmetric Y6‐like acceptor, BTP‐FCl‐FCl, is designed and synthesized to match the recently reported high performance small molecule donor BTR‐Cl, and a record efficiency of 15.3% for single‐junction binary ASM OSCs is achieved. BTP‐FCl‐FCl features a F,Cl disubstitution on the same end group affording locally asymmetric structures, and so has a lower total dipole moment, larger average electronic static potential, and lower distribution disorder than those of the globally asymmetric isomer BTP‐2F‐2Cl, resulting in improved charge generation and extraction. In addition, BTP‐FCl‐FCl based active layer presents more favorable domain size and finer phase separation contributing to the faster charge extraction, longer charge carrier lifetime, and much lower recombination rate. Therefore, compared with BTP‐2F‐2Cl, BTP‐FCl‐FCl based devices provide better performance with FF enhanced from 71.41% to 75.36% and J sc increased from 22.35 to 24.58 mA cm−2, leading to a higher PCE of 15.3%. The locally asymmetric F, Cl disubstitution on the same end group is a new strategy to achieve high performance ASM OSCs., Single‐junction all‐small‐molecule organic solar cells with record high PCEs of 15.3% have been demonstrated by a locally asymmetric electron acceptor BTP‐FCl‐FCl and BTR‐Cl donor.

This paper examined the influence of magnesium on denitrifying sludge. Two up-flow anaerobic sludge bed (UASB) reactors were used in the study. R1 was continuously supplied with 50 mg L−1 of divalent magnesium in the wastewater and R0 was used as a control without magnesium. On the 258th day, the sludge properties in R0 and R1 were analyzed when the nitrogen loading rates were both 36.0 kgN m−3 d−1 and the nitrogen removal rates of R0 and R1 were 33.8 and 34.6 kgN m−3 d−1, respectively. The diameters of R0 and R1 were 0.95and1.35 mm, settling velocity (74.5 ± 20.8 and102.0 ± 22.6 m h−1), extracellular polymeric substance (60.8 ± 2.1 and76.0 ± 2.7 mg g−1VSS)and specific denitrifying activity (794.4 ± 9.6 and825.6 ± 4.9 mgN d−1) were also compared. These results addressed that the addition of magnesium to denitrifying reactor is an effective alternative to enhance sludge properties.

An anaerobic ammonium oxidation (anammox) reactor was operated with two feeding regimes. In stage 1, the reactor was operated as a common anaerobic baffled reactor (CABR) (constant flow direction), whereas in stage 2, the reactor was modified as a flow switched anaerobic baffled reactor (FSABR) with the flow direction switching every 10 days. Adjusting the feeding regime resulted in an increase in the average nitrogen loading rate (from 1.62 to 1.80 kgN m −3 d −1 ) and nitrogen removal efficiency (from 75.4 to 83.1%). In addition, a maximum nitrogen removal rate of 3.49 kgN m −3 d −1 was obtained in stage 2, compared with 3.00 kgN m −3 d −1 in stage 1. The sludge properties were also enhanced; from stage 1 to stage 2, the specific anammox activity increased by more than 5-fold, the settling velocity increased from 64.1 to 71.9 m h −1 , and the average particle diameter increased from 0.8 to 2.3 mm. However, there was minimal variation in the heme c content. The maximum substrate removal rates in stages 1 and 2 were 4.28 and 46.38 kgN m −3 d −1 when fitted by the Stover-Kincannon model, respectively. The results indicate that the FSABR performance was significantly enhanced compared with the CABR.

The present study was designed to develop a sensitive and selective specific high performance liquid chromatography (HPLC)-tandem mass spectrometric method (MS/MS) for the determination of ligupurpurosides B and C in rat plasma. The samples were prepared after protein precipitation and analyzed by liquid chromatography equipped with a C18 column interfaced with a triple quadrupole tandem mass spectrometer using ESI as the ionization source in the negative ion mode. The mobile phase consisted of water (0.01 % formic acid)-methanol (57 : 43, V/V) at the flow rate of 0.3 mL·min(-1). The analytes and internal standard acteoside were both detected by use of multiple reaction monitoring mode. The total run time was 6.0 min. The method was linear in the concentration range of 2.5-500.0 ng·mL(-1) and the lower limit of quantifiation (LLOQ) was 2.5 ng·mL(-1). The intra-day and inter-day relative standard deviations across three validation runs over the entire concentration range were less than 9.8 %. The accuracy determined at three concentrations was within ± 6.1% in terms of relative error. In conclusion, this assay offers advantages in terms of expediency and suitability for the analysis of ligupurpuroside B and ligupurpuroside C in various biological fluids.

Starvation of biomass is common in the biological wastewater industries. To investigate the influence of starvation on the sludge characteristics and reactivation performance of the anaerobic ammonium oxidation (anammox) process, the starvation process of high-activity anammox granules over 50 days and the subsequent reactivation characterization of the granules were evaluated in two upflow anaerobic sludge blanket (UASB) reactors at 20 °C and 4 °C, respectively. The results showed that the starvation temperature had a significant impact on the morphological and physical properties. Anammox granules stored at 4 °C achieved a relatively low decay rate, excellent nitrogen removal capacity, and a low protein-to-polysaccharide (PN/PS) ratio after reactivation. Those results demonstrated that 4 °C was more suitable for the maintenance of structural integrity and granule stability during long-term starvation. The nitrogen removal performance of anammox granules after starvation could be recovered after 4 days of operation, and the anammox activity could be fully restored within 8 days. Furthermore, anammox granules preserved at 4 °C obtained a better recovery performance than those at 20 °C. In summary, anammox granules could be stored up to 50 days without running the risk of losing the integrity of the granules and metabolic potentials. And anammox performance after prolonged starvation could be fully revived.

One-dimensional core-shell nanowire materials have recently received great attention as durable catalysts for water splitting. Herein we report the facile and rapid synthesis of ultralong Fe(OH)3:Cu(OH)2 core-shell nanowires grown in situ on an open 3D electrode to function as a highly efficient electrocatalyst for water oxidation. It only requires an overpotential of ∼365 mV to reach a 10 mA cm-2 current density in 1.0 M KOH. As far as we know, this shows the best result amongst Cu-based heterogeneous OER systems reported to date.

Accumulating data demonstrated that hepatic endoplasmic reticulum (ER) stress was involved in the pathogenesis of liver fibrosis. Long-term chronic hepatocyte death contributed to liver fibrosis initiation and progression. Previous researches reported that ER stress sensor inositol-requiring enzyme 1 alpha (IRE1α) was first activated in the process of liver fibrosis. STF-083010 was an IRE1α RNase specific inhibitor. This study aimed to explore the effects of STF-083010 on carbon tetrachloride (CCl4)-induced liver injury and subsequent liver fibrosis. Mice were intraperitoneally (i.p.) injected with CCl4 (0.15 ml/kg) for 8 weeks. In STF-083010+CCl4 group, mice were injected with STF-083010 (30 mg/kg, i.p.), twice a week, beginning from the 6th week after CCl4 injection. CCl4 treatment markedly enhanced the levels of serum ALT, TBIL, DBIL and TBA, and STF-083010 had obviously extenuated CCl4-induced exaltation of ALT, DBIL, and TBA levels. CCl4-induced hepatic hydroxyproline and collagen I, major indicators of liver fibrosis, were alleviated by STF-083010. Additionally, CCl4-induced α-smooth muscle actin, a marker for hepatic stellate cells activation, was obviously attenuated in STF-083010-treated mice. Moreover, CCl4-induced upregulation of inflammatory cytokines was suppressed by STF-083010. Mechanistic exploration found that hepatic miR-122 was downregulated in CCl4-treated mice. Hepatic MCP1, CTGF, P4HA1, Col1α1, and Mmp9, target genes of miR-122, were upregulated in CCl4-treated mice. Interestingly, STF-083010 reversed CCl4-induced hepatic miR-122 downregulation. Correspondingly, STF-083010 inhibited CCl4-induced upregulation of miR-122 target genes. This study provides partial evidence that STF-083010 alleviated CCl4-induced liver injury and thus protected against liver fibrosis associated with hepatic miR-122.

Background Parkinson’s disease (PD) is one of the most common neurodegenerative diseases, neuropathologically characterized by misfolded protein aggregation, called Lewy bodies and Lewy neurites. PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease. Methods In order to study PD pathology in the colon, we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein (α-syn) fused with the green fluorescent protein (GFP), under the endogenous mouse α-syn promoter. Results We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner’s (submucosal) and Auerbach’s (myenteric) plexuses of the colon. Additionally, the phosphorylation of α-syn at serine 129 also increased with age and the aggregation of α-syn-GFP coincided with the appearance of motor deficits at 9 months of age. Furthermore, α-syn (-GFP) distinctly co-localized with different subtypes of neurons, as identified by immunohistochemical labeling of vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and calretinin. Conclusions Our results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model, which coincide with the appearance of motor deficits. Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction. Electronic supplementary material The online version of this article (10.1186/s40035-018-0118-8) contains supplementary material, which is available to authorized users.

Perforalactone A (1), a new 20S quassinoid with a unique cagelike 2,4-dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X-ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid-type natural products are also discussed.

A sensitive and simple liquid chromatography–tandem mass spectrometric (HPLC-MS/MS) method for the determination of corilagin in rat plasma has been developed. Samples were prepared with protein precipitation method and analyzed with a triple quadrupole tandem mass spectrometer. We employed negative electrospray ionization as the ionization source and the analytes were detected in multiple reaction monitoring mode. Separation was achieved on a C8 column eluted with mobile phase consisting of methanol–0.1% formic acid in a gradient mode at the flow rate of 0.3 mL/min. The total run time was 7.0 min.This method was proved to have good linearity in the concentration range of 2.5–1000.0 ng/mL. The lower limit of quantification of corilagin was 2.5 ng/mL. The intra- and inter-day relative standard deviationa across three validation runs for four concentration levels were both

BACKGROUND: We have investigated the potential anticancer effects of karanjin, a principal furanoflavonol constituent of the Chinese medicine Fordia cauliflora, using cytotoxic assay, cell cycle arrest, and induction of apoptosis in three human cancer cell lines (A549, HepG2 and HL-60 cells). RESULTS: MTT cytotoxic assay showed that karanjin could inhibit the proliferation and viability of all three cancer cells. The induction of cell cycle arrest was observed via a PI (propidium iodide)/RNase Staining Buffer detection kit and analyzed by flow cytometry: karanjin could dose-dependently induce cell cycle arrest at G2/M phase in the three cell lines. Cell apoptosis was assessed by Annexin V-FITC/PI staining: all three cancer cells treated with karanjin exhibited significantly increased apoptotic rates, especially in the percentage of late apoptosis cells. CONCLUSION: Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis. This compound may be effective clinically for cancer pharmacotherapy.

A sensitive and selective high performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method for the simultaneous determination of kudinoside A, kudinoside D and kudinoside F in human plasma has been firstly developed. Samples were prepared after protein precipitation and analyzed on a C18 column interfaced with a triple quadrupole tandem mass spectrometer. Negative electrospray ionization was employed as the ionization source. The mobile phase consisted of acetonitrile-water (35:65) at the flow rate of 0.3mL/min. The analytes and internal standard Ginsenoside Rb1 were both detected by use of multiple reaction monitoring mode. The method was linear in the concentration range of 2.5-1000.0ng/mL. The lower limit of quantification (LLOQ) was 2.5ng/mL. The intra-and inter-day relative standard deviation across three validation runs over the entire concentration range was less than 12.4%. The accuracy determined at three concentrations was within ±4.9% in terms of relative error. The total run time was 7.0min. This assay offers advantages in terms of expediency, and suitability for the analysis of kudinoside A, kudinoside D and kudinoside F in various biological fluids.

The absolute and relative pool sizes of deoxyribonucleotides (dRNs) are essential in DNA replication fidelity, DNA damage and repair. We found in this study that although DNA damage induced by methyl methanesulfonate (MMS) seemed similar in cancer (HepG2) and normal (LO2) cells, more extensive alterations in ribonucleotides (RNs) and dRNs pools occurred in HepG2 cells indicating that HepG2 cells were more vigilant to DNA damage. After 10 h repair, RNs pools were still severely perturbed in LO2 cells. Compared to LO2 cells, deoxyribonucleotide triphosphates (dNTPs) pools in HepG2 cells elevated by more folds which could facilitate more efficient DNA repair and improve survival probability following DNA damage, although this should definitely lead to higher mutation rates. DNA repair was more efficient in HepG2 cells at S phase and it partly came to an end while DNA repair was still uncompleted in LO2 cells outside S phase. In conclusion, our results demonstrated that HepG2 and LO2 cells presented many differences in nucleotide metabolism, cell cycle checkpoints and DNA repair pathways in response to DNA damage, which could be potential targets for cancer treatment.