Search

Key Message: Reducing endogenous CK levels accelerates fruit ripening in tomato by regulating ethylene biosynthesis and signalling pathway. Tomato is a typical climacteric fruit and is recognized as one of the most important horticultural crops globally. The ripening of tomato fruits is a complex process, highly regulated by phytohormones. Cytokinin (CK) is a hormone that primarily impacts the early development of fruit, however its influence on fruit ripening has not been thoroughly investigated. In this study, we used both wild-type Micro-Tom and transgenic tomato plants that overexpress AtCKX2, a CK degradation gene driven by the fruit-specific promoter Tfm7, to investigate the effect of CK on tomato fruit ripening. Our findings revealed that reducing endogenous CK levels in transgenic plants can accelerate the ripening process of tomato fruits. Premature activation of ethylene biosynthetic genes and ripening regulator genes was upregulated in CK-deficient fruits. Moreover, the application of exogenous ethylene inhibitors resulted in delayed fruit ripening in CK-deficient fruits. These results together suggest that CK plays a negative role in tomato fruit ripening by affecting the ethylene pathway., Competing Interests: Declarations. Conflict of interest: The authors have not disclosed any competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It is challenging yet critical to differentiate between hemorrhagic transformation (HT) and contrast extravasation on non-contrast-enhanced computed tomography (NCCT) scans following mechanical thrombectomy (MT) in patients with acute ischemic stroke. We propose a new method called the ratio of maximum density values (RMDV) to minimize the confusion of contrast extravasation and to evaluate the diagnostic significance of RMDV in predicting HT on immediate post-interventional NCCT scans., Methods: We conducted a retrospective analysis of the prospective patients' database who received MT for acute ischemic stroke caused by occlusion of the intracranial large artery and showed postinterventional cerebral hyperdensities (PCHDs) on NCCT scans immediately after MT. Based on the subsequent NCCT scans, we divided patients with PCHDs into the HT and the non-HT groups. The clinical characters and radiological details were collected and compared to the two groups. We assessed the ability of RMDV >1 to predict HT by analyzing the receiver operating characteristic curve., Results: One hundred and three patients showed PCHDs; 58 (56.31%) were classified as HT, while 45 (43.69%) were classified as non-HT. The only notable distinction between the two groups was the proportion of RMDV >1 in the HT group. The correlation between HT and RMDV >1 with an area under the curve of 0.826 (95% confidence interval, 0.739 to 0.894). The sensitivity, specificity, positive, and negative predictive values of RMDV >1 on NCCT for predicting HT were 89.66, 75.56, 82.54, and 85.00%, respectively., Conclusion: The utilization of RMDV >1 on immediate NCCT scans after MT can predict early HT with good sensitivity and specificity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiao, Zheng, Wei and Zhao.)

In this study, an autogenous N-doped biochar derived from Chlorella (CVAC) was prepared with NaOH as activator at 800 °C. The surface structural properties of CVAC and the adsorption performance of CVAC on tetracycline (TC) under different adsorption variables were analyzed and investigated using different characterization methods. The results showed that the specific surface area of CVAC was 491.16 m 2  g -1 and the adsorption process was in accordance with Freundlich model and pseudo-second-order kinetic model. The maximum adsorption capacity of TC was 310.696 mg g -1 at pH 9 and 50 °C, and it was mainly physical adsorption. Furthermore, the cyclic adsorption-desorption behavior of CVAC using ethanol as eluent was evaluated and the feasibility of its long-term application was explored. CVAC also showed good cyclic performance. The variation of ΔG° and ΔH° confirmed that the adsorption of TC by CVAC was a spontaneous heat absorption process., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shuang Wang reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Chemical resources and techniques have long been used in the history of bulk polyester production and still dominate today's chemical industry. The sustainable development of the polyester industry demands more renewable resources and environmentally benign polyester products. Accordingly, the rapid development of biotechnology has enabled the production of an extensive range of aliphatic and aromatic polyesters from renewable bio-feedstocks. This review addresses the production of representative commercial polyesters (polyhydroxyalkanoates, polylactic acid, poly ε-caprolactone, polybutylene succinate, polyethylene terephthalate, polybutylene terephthalate, polypropylene terephthalate, polyethylene furandicarboxylate, polypropylene furandicarboxylate, and polybutylene furandicarboxylate) or their monomers (lactic acid, succinic acid, 1,4-butanediol, ethylene glycol, terephthalic acid, 1,3-propanediol, and 2,5-furandicarboxylic acid) from renewable bioresources. In addition, this review summarizes advanced biotechniques in the treatment of polyester wastes, representing the near-term trends and future opportunities for waste-to-value recycling and the remediation of polyester wastes under sustainable models. For future prospects, it is essential to further expand: non-food bioresources, optimize bioprocesses and biotechniques in the preparation of bioderived or biodegradable polyesters with promising: material performance, biodegradability, and low production cost.

Marine organisms need to adapt to improve organismal fitness under ocean acidification (OA). Recent studies have shown that marine calcifiers can achieve acclimation by stimulating calcium binding/signaling pathways. Here, a CaM-like gene (CgCaLP-2) from oyster Crassostrea gigas which typically responded to long-term CO 2 exposure (two months) rather than short-term exposure (one week) was characterized. The cloned cDNA was 678 bp and was shorter than the retrieved sequence from NCBI (1125 bp). The two sequences, designated as CgCaLP-2-v1 and CgCaLP-2-v2, were demonstrated to be different splice variants by the genome sequence analysis. Western blotting analysis revealed two bands of 23 kD and 43 kD in mantle and hemocytes, corresponding to predicted molecular weight of CgCaLP-2-v1 and CgCaLP-2-v2, respectively. The isoform CgCaLP-2-v1 (the 23 kD band) was highly stimulated in response to long-term CO 2 exposure (42-day and 56-day treatment) in hemocytes and mantle tissue. The fluorescence signal of CgCaLP-2 in mantle and hemocytes became more intensive after long-term CO 2 exposure. Besides, in hemocytes, CgCaLP-2 presented a higher localization on the nuclear membrane after long-term CO 2 exposure (56 d). The target gene network of CgCaLP-2 was predicted, and a transcription factor (TF) gene annotated as Homeobox protein SIX4 (CgSIX4) showed a similar expressive trend to CgCaLP-2 during CO 2 exposure. Suppression of CgCaLP-2 via RNA interference significantly reduced the mRNA expression of CgSIX4. The results suggested that CgCaLP-2 might mediate the Ca 2+ -CaLP-TF signal transduction pathway under long-term CO 2 exposure. This study serves as an example to reveal that alternative splicing is an important mechanism for generation multiple protein isoforms and thus shape the plastic responses under CO 2 exposure, providing new insight into the potential acclimation ability of marine calcifiers to future OA., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, a paper-based enzyme biosensor for hypoxanthine (Hx) was developed, enabling visual and one-step fish freshness detection. Xanthine oxidase and horseradish peroxidase were immobilized on nitrocellulose membranes with 3,3',5,5'-tetramethylbenzidine to output the colour signal. Chitosan oligosaccharide lactate-modified nitrocellulose membranes entrapped the dual-enzyme system and exhibited excellent microfluidic aggregation effect. The developed enzyme biosensor produced a linear response of 0.01-0.16 mmolL -1 with a detection limit of 8.22 μmolL -1 , and was selective for Hx with recoveries of 96.13-103.11 % for fish samples. These biosensors were attached directly to the surface of fish samples and the colour was revealed within 3 min. Colour signals can be judged by the naked-eye to distinguish between fresh and spoiled fish samples and analyzed by a smartphone for quantitative analysis. The biosensor shows great potential as a powerful pattern- and reagent-free device for on-site freshness evaluation of fish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Composite functional materials offer promising opportunities for the development of tailored adsorbents with enhanced bioremediation potential towards toxic, carcinogenic endocrine disrupters such as Bisphenol A (BPA). Copyrolysis of microalga Chlorella sp. (CH) alkali lignin (L) with K 2 CO 3 impregnation yielded a carbon-based composite (CHL-AC) with a micro-mesoporous structure of 0.643 cm 3 /g, surface area of 1414 m 2 /g, and BPA adsorption capacity of Q max 316.858 mg/g. Enhanced BPA removal efficiency indicated a positive synergistic effect upon a combination of L and CH, resulting in a 73.24 % removal efficiency compared with the individual carbon components of 52.33 % for L-AC and 67.35 % for CH-AC. The kinetics and equilibrium results were described well by the pseudo second-order kinetic model and Freundlich isotherm, respectively. This paper elucidates the blending of microalgae and lignin into high-value carbon composite material, CHL-AC, with immense potential for the treatment of BPA-contaminated waters to contribute to Goal 6 (clean water and sanitation)., Competing Interests: Declaration of competing interest We declare no conflicts of interest associated with submission., (Copyright © 2022. Published by Elsevier B.V.)

Color indicator films for fish freshness were fabricated by incorporating κ-carrageenan (CAR) polymer with red grape skin extract (GSE) as a pH-sensing agent and silver nanoparticles (AgNPs) as an antimicrobial agent. Anthocyanins in GSE exhibited distinguished pH responsive color changes. GSE and AgNPs were well compatible with CAR with intramolecular interactions, approved by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis, thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC). GSE-containing films displayed distinguished color changes in response to pH variations and volatile ammonia. Enhanced UV blocking ability and strong antioxidant activity were revealed for GSE included films without sacrificing the physico-chemical properties of the CAR film. Films containing AgNPs showed improved mechanical strength and strong antimicrobial ability against both Escherichia coli and Staphylococcus aureus. The CAR/AgNPs/GSE film displayed a distinctive color change corresponding to changes in the total volatile basic nitrogen (TVB-N) of fish during storage. In addition, the CAR/AgNPs/GSE film showed excellent color stability to consecutive UV exposure and its storage time at 25 °C is expected to be at least 240 days, which indicates that it has high potential as an intelligent food freshness indicator film., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Activated carbon (ENAC) was prepared by NaOH activation, using macroalgae (Enteromorpha clathrate) as raw material. The prepared activated carbon has a large surface area (1238.491 m 2 g -1 ) and its total pore volume and average pore size are 0.6823 cm 3 g -1 and 2.2038 nm, respectively. The ENAC was characterized by SEM, FTIR, BET and XPS. The effects of contact time (0-960 min), initial tetracycline (TC) concentration (50-500 mg L -1 ), temperature (30-50 °C) and initial pH (2-11) on TC adsorption were evaluated. The adsorption isotherm and adsorption kinetics were discussed. Results showed that the adsorption isotherm was the Langmuir model, and the adsorption process can be described by the pseudo-second-order model. The N 2 adsorption-desorption isotherm was type IV, indicating that the activated carbon had mesoporous structure. Thermodynamic analysis showed that the adsorption process was endothermic and spontaneous. The maximum adsorption capacity of TC was 381.584 mg g -1 . Density functional theory (DFT) was used to simulate and analyze the adsorption process, and the influence of different types of N on the adsorption was expounded. The results showed that there are electrostatic interactions, π-π interactions and hydrogen bonding between the adsorbent and TC. These results indicated that the prepared ENAC had a great application prospect in the removal of antibiotics from aqueous solution., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A FeCl 3 -activated seaweed carbon/MCM-41/alginate hydrogel composite (ECAC/MCM-41/ ALG) cross-linked with calcium chloride (2% CaCl 2 ) was synthesized for the biosorption of bisphenol A (BPA) plasticizer and basic blue (BB) dye. Biosorption uptakes of BPA and BB were performed in a batch mode with varying solution pH from 3 to 11, initial sorbate concentration from 25 to 300 mg/L, reaction time from 0 to 10 h, and biosorption temperature from 30 to 50 °C. The maximum BPA and BB uptake mechanisms were fast, which occurred within contact times of 1 and 2 h with monolayer coverage capacities of 222.32 and 190.11 mg/g at 50 °C, respectively. Cyclic biosorption/desorption behavior was evaluated via an ethanol elution to evaluate the feasibility of the ECAC/MCM-41/ALG for long-term application. Results revealed the biosorption renewability for five cycles up to 80% of the newly synthesized hydrogel composite for the purification of industrial wastewater laden with emerging contaminants., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiao, Huang, Liu, Zhao and Wei.)

Au nanoparticles (AuNPs) (10-15 nm in size) were prepared and deposited on the surfaces of silica particles functionalized using 3-aminopropyltriethoxysilane as the seeds under mild conditions. Then, Au seeds grew further and formed nanosheets by the method of gold chloride hydrate reduction. 3, 5-dimethylphenyl isocyanate derivative of cellulose as chiral selector was coated on the surfaces of SiO2/Au. The obtained spheres possessed a sandwich structure in which silica bead, the packed Au NPs monolayer and cellulose derivative were the core, the interlayer and the shell, respectively. The resultant packing material was evaluated by high-performance liquid chromatography (HPLC) as chiral stationary phase (CSP). The separations of nine pairs of enantiomers were achieved in the normal-phase liquid chromatography mode. The results showed that the new CSP has sufficient interaction with the analytes due to the existence of AuNPs on silica surfaces compared with coated cellulose-silica column., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Simple, fast and efficient method for on-site detection of meat adulteration is of increasing demand in low-resource regions. Here, a direct and visual denaturation bubble-mediated strand exchange amplification method (SEA) was developed to detect meat adulteration by targeting the mitochondrial sequence from duck, which required only a heating block. The method allowed detecting as low as 10 pg/μL duck DNA and 0.1% duck meat in binary mixtures, sufficiently meeting the demand of meat adulteration detection. Notably, the method realized instrument-free readout by significant color discrimination of positive and negative results. By coupling with fast DNA release, a direct SEA method was developed and reduced the whole detection time to 1 h, eliminating complex DNA extraction process. The developed method provided a promising strategy with integration of fast sample lysis, miniaturized reaction platform and visual readout for meat adulteration, especially suitable for low resource point-of-care settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Acetyl-CoA is a precursor for phloroglucinol (PG), and pyruvate is one of the sources of intracellular acetyl-CoA. Therefore, enhancing intracellular pyruvate levels may help to improve the anabolic pathway of PG., Results: In this study, the effects of phosphoenolpyruvate carboxykinase (PckA, encoded by pckA) or triosephosphate isomerase (TpiA, encoded by tpiA) overexpression on the production of PG were studied. Overexpression of pckA or tpiA could enhance the pyruvate anabolic pathway in shake-flask culture compared to the control strain, and the concentration of PG also increased by 44% and 92%, respectively. In addition, the acetate levels were all down regulated by the overexpression of the two genes to some extent and lower acetate level resulted in lower ATP pool and higher survival rate., Conclusions: These results indicate that overexpression of pckA or tpiA can enhance the pyruvate "pool" and PG production in Escherichia coli, which provides a new reference for further increasing the production of PG.

Motivated by the desire for simple, rapid and highly sensitive DNA detection, we presented a signal-on electrochemical DNA (E-DNA) sensing strategy utilizing cooperative proximity hybridization based on a G-quadruplex (G4) probe labeled with the SH, which could specifically hybridize with its target DNA in homogenous solution. In the presence of target DNA, proximity hybridization was triggered to form a Y-shaped complex and the SH was released from G4 probe stem, companied by chemisorption on the electrode surface through Au-S binding when applied a positive potential, which brought Fc labeled on the signal probe close to the electrode surface. Thus, electrochemical signal dramatically increased, ensuring the highly sensitive "signal-on" assay. Such an E-DNA sensing strategy allows for ultrasensitive DNA detection with a detection limit as low as 2.82 × 10 -15  M and a wide linear response from 1.0 × 10 -9 to 1.0 × 10 -15  M. In addition, the powerful discriminating ability of the mismatched DNA from the perfect matched target DNA was also demonstrated. More importantly, this homogenous proximity hybridization strategy could expand to colorimetric assay by incorporating G4 probe with hemin to form DNAzyme, which could effectively catalyze ABTS to generate a visual color change. Taking the joint advantages of G4 stem-loop probe and homogenous proximity hybridization, this sensing strategy exhibits greatly enhanced sensitivity and excellent specificity, making it a promising strategy for point-of-care testing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The DNA tetrahedron has developed a broad spectrum of applications in biosensor construction thanks to its excellent mechanical rigidity and structural stability. However, how to construct a highly sensitive biosensor using a DNA tetrahedron is still a challenge. In this work, an ultrasensitive electrochemical biosensor based on a DNA tetrahedral nanostructure was developed with the help of synergy from proximity-dependent hybridization. To decrease the steric hindrance of DNA tetrahedra to proximity-dependent hybridization, the detection signal was set on the inclined side chain structure of a DNA tetrahedral sensing system. Additionally, when the target hybridized with the DNA probe, the ferrocene (Fc) labeled on the end of the DNA probe was driven close to the surface of the biosensor, providing a sensitive faradaic current. The experimental results exhibited a good linear relationship from 1 fM to 10 pM with a linear correlation coefficient of 0.9977, and a high sensitivity with a detection limit of 0.2 fM. Our DNA biosensor also showed good stability according to electrode characterization and target detection at different time scales and the anti-jamming capabilities in a complicated biological extraction environment were excellent. The electrochemical sensing system established here has greatly improved the detection sensitivity of a DNA biosensor based on a DNA tetrahedron, which will further promote its practical applications.

Driven by a bright prospect for rapid, portable and cost-effective point-of-care testing, an assembled Pasteur pipette device to integrate nucleic acid extraction, amplification and detection was developed to detect B. cereus in a sample-to-answer format. Denaturation Bubble-mediated Strand Exchange Amplification (SEA) was chosen to perform isothermal amplification because it requires only a pair of primers and one Bst DNA polymerase. The established SEA can detect as low as 1.0 × 10 -13  M genomic DNA of B. cereus, which was comparable with the previously reported method for B. cereus detection. The assembled Pasteur pipette allows sample-to-answer diagnostic in a simple, low-cost, portable, and disposable format. The inherent function of Pasteur pipette enables direct liquid handling without the need of extra pipettes, syringes or pumps. Visual readout was achieved by using a pH sensitive dye, further simplifying result judgment process. The detection limit for B. cereus is 1.0 × 10 4  CFU/mL in pure cultures, while the detection limit in artificially contaminated milk is 1.0 × 10 5  CFU/mL without enrichment and 1.0 × 10 0  CFU/mL following 12 h enrichment. Considering that typical cell counts in food samples associated to food poisoning are 1.0 × 10 5 to 1.0 × 10 8  CFU per gram/milliliter B. cereus, our Pasteur pipette is enough sensitive for answer-to-sample diagnosis of B. cereus even directly from foods without enrichment. The whole diagnostic procedure could be completed within 50 min, dramatically decreasing the detection time. In a word, the assembled Pasteur pipette device, combined with a homemade metal bath, possesses great potential for sample-to-answer application in resource-limited settings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Meat screening plays a significant role in human health and religion. But the identification methods for beef were little reported. In this work, a simple colorimetric method based on denaturation bubble-mediated strand exchange amplification (SEA) was developed for the rapid and sensitive identification of beef. The whole strategy was performed on a portable metal bath and the distinguishable color between positive and negative controls was observed directly by the naked eyes. The feasibility using crude extraction samples by a heating treatment in PBS for 2 min was evaluated in duck spiked by beef. The result demonstrated that the developed method could identify as low as 1% (w/w) beef/duck within 50 min. Meanwhile, the results showed the method had a good repeatability and specificity. Therefore, this assay allows for the rapid, sensitive, specific detection of beef, and can be recommended as an effective, promising strategy for on-site meat identification.

M. pneumoniae infection is often ignored due to its similar clinical symptom with respiratory tract infections caused by bacteria or viruses, and thus leading to misdiagnosis and delayed treatment. It is critical to develop a rapid, sensitive and specific diagnosis method. Denaturation Bubble-mediated Strand Exchange Amplification (SEA) was established, which is an isothermal method with only a primer pair and one Bst DNA polymerase. Notably, colorimetric SEA assay was developed with simple visual readout, making instrument-independent in detection step. The method could detect as low as 1.0 × 10 4 copies/mL genomic DNA within 60 min. Considering that more than 80% infected patients have 1.0 × 10 5 -1.0 × 10 7 copies/mL M. pneumonia DNA, SEA is available for the practical diagnosis of M. pneumoniae in clinical specimens. Through comparing 224 sputum specimens, excellent performance of SEA assay with 90.48% sensitivity and 100% specificity relative to real-time PCR was observed. Compared with LAMP, a comparable sensitivity and low false positive rate was observed for SEA method. Therefore, SEA is a promising method for detecting M. pneumoniae directly from clinical specimens, which is especially suitable for point-of-care testing in primary care facilities and resource-limited settings with minimal equipment and technological expertises.

Starting from the phase II clinical FGFR inhibitor lucitanib (2), we conducted a medicinal chemistry approach by opening the central quinoline skeleton coupled with a scaffold hopping process thus leading to a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives. Compound 25a was identified to show selective and equally high potency against FGFR1/2 and VEGFR2 with IC 50 values less than 5.0 nM. Significant antiproliferative effects on both FGFR1/2 and VEGFR2 aberrant cancer cells were observed. In the SNU-16 xenograft model, compound 25a showed tumor growth inhibition rates of 25.0% and 81.0% at doses of 10 mg/kg and 50 mg/kg, respectively, with 5% and 10%body weight loss. In view of the synergistic potential of FGFs and VEGFs in tumor angiogenesis observed in preclinical studies, the FGFR/VEGFR2 dual inhibitor 25a may achieve better clinical benefits., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

PI3Kδ is a key component in the aberrant signaling transduction in B cell malignancy, therefore specific targeting PI3Kδ has become an attractive molecularly targeted therapy for chronic lymphocytic leukemia (CLL). Herein, we describe the discovery and optimization of a series of 5-alkynyl substituted PI3Kδ inhibitors based on the first FDA-approved inhibitor idelalisib. Compound 8d bearing the 1-morpholinohex-5-yn-1-one moiety as the C5-substituent was identified to have high potency against PI3Kδ (3.82 nM) and SU-DHL-6 cells (7.60 nM), respectively. It was 154-fold selective over PI3Kα, 133-fold selective against PI3Kβ, and 24-fold selective against PI3Kγ. Treatment of MOLT-4 and SU-DHL-6 cells with compound 8d for 1 h resulted in reduction of phosphorylation of both Akt (S473) and its downstream S6k1 (T389) in a concentration-dependent manner. Compound 8d showed potent anti-proliferative activity as well against T lymphoblast MOLT-4, suggesting its potential activity in T-cell leukemia., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

A facile strategy based on self-assembly of Au nanoparticles (AuNPs) (60±10nm in size) on the surfaces of amino-functionalized porous silica spheres under mild conditions was proposed. The resulting material possessed a core-shell structure in which AuNPs were the shell and silica spheres were the core. Then, thiolated-β-cyclodextrin (SH-β-CD) was covalently attached onto the AuNPs as chiral selector for the enantioseparation. The resultant packing material was evaluated by high-performance liquid chromatography (HPLC). The separations of nine pairs of enantiomers were achieved by using the new chiral stationary phase (CSP) in the reversed-phase liquid chromatography (RPLC) mode, respectively. The results showed the new CSP have more sufficient interaction with the analytes due to the existence of AuNPs on silica surfaces, resulting in faster mass transfer rate, compared with β-CD modified silica column. The result shed light on potential usage of chemical modified NPs as chiral selector for enantioseparation based on HPLC. In addition, the new phase was also used in hydrophilic interaction liquid chromatography (HILIC) to separate polar compounds and highly hydrophilic compounds., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A bench-scale constructed wetland combined with microbial electrochemical technology (MET-CW) was run for 400days with groundwater contaminated with benzene, methyl-tert-butyl ether (MTBE), and ammonium (NH4(+)). Four vertically stacked anode modules were embedded into a sand bed and connected with a stainless steel cathode placed in an open water pond. In the zone of presence of anode modules, significantly more benzene and MTBE were removed in the MET-CW compared to the control CW without MET in the first 150 operation days. Benzene was identified as primary electron donor at the anode. Benzene removal and current densities were linearly correlated, implying the potential of the system for electrochemically monitoring benzene biodegradation. Compound-specific isotope analysis (CSIA) indicated that benzene was initially activated by monohydroxylation forming intermediates which were subsequently oxidized accompanied by extracellular electron transfer, leading to current production. NH4(+) removal was not stimulated by MET., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Chronic lymphocytic leukemia (CLL) remains the most incurable leukemia. Early chemotherapeutic treatments, including alkylating agents, purine nucleoside derivatives, and immunotherapeutic antibodies, only show limited benefits for patients but severe off-target related side effects. Recent advances in understanding of the critical molecular pathways of regulating proliferation and survival of B-CLL cells have spurred a new therapeutical strategy by selectively targeting phosphoinositide 3-kinase delta (PI3Kδ). Idelalisib, a first-in-class PI3Kδ-selective small molecule has received the FDA's fast-track approval in July of 2014 as a new treatment of CLL, indolent B-cell non-Hodgkin's lymphoma, and relapsed small lymphocytic lymphoma. Undoubtedly, the success of idelalisib has provided a solid support in the development of PI3Kδ-specific inhibitors and reformed the concept of treating CLL. However, the number of reported selective inhibitors of PI3Kδ is very limited and very few have advanced into clinical trials. The mechanism of their actions remains elusive. More profound understanding on the modes of action of new PI3Kδ inhibitors will further validate the PI3Kδ-targeting strategy, and help to identify biomarkers capable of stratifying patients who will most likely benefit from the therapy., (© 2015 Wiley Periodicals, Inc.)