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As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, a series of new pyrazole acyl(thio)urea compounds containing a diphenyl motif were designed and synthesized. Their structures were confirmed by 1 H NMR, HRMS, and single X-ray crystal diffraction analysis. Most of these compounds possessed excellent activity against 10 fungal plant pathogens at 50 μg mL -1 , especially against Rhizoctonia solani, Alternaria solani , Sclerotinia sclerotiorum , Botrytis cinerea , and Cercospora arachidicola . Interestingly, compounds 3-(difluoromethyl)-1-methyl- N -((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1 H -pyrazole-4-carboxamide ( 9b , EC 50 = 0.97 ± 0.18 μg mL -1 ), 1,3-dimethyl- N -((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1 H -pyrazole-4-carboxamide ( 9a , EC 50 = 2.63 ± 0.41 μg mL -1 ), and N -((4'-chloro-[1,1'-biphenyl]-2-yl)carbamoyl)-1,3-dimethyl-1 H -pyrazole-4-carboxamide ( 9g , EC 50 = 1.31 ± 0.15 μg mL -1 ) exhibited activities against S. sclerotiorum that were better than the commercial fungicide bixafen (EC 50 = 9.15 ± 0.05 μg mL -1 ) and similar to the positive control fluxapyroxad (EC 50 = 0.71 ± 0.11 μg mL -1 ). These compounds were not significantly phytotoxic to monocotyledonous and dicotyledonous plants. Structure-activity relationships (SAR) are discussed by substituent effects/molecular docking, and density functional theory analysis indicated that these compounds are succinate dehydrogenase inhibitors.

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m 2 ), normal weight (BMI between 18.5 and 24.9 kg/m 2 ), overweight (BMI between 25.0 and 29.9 kg/m 2 ), and obese (BMI≥30.0 kg/m 2 ). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively ( P< 0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group ( OR =1.30, 95% CI 1.13-1.49, P <0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P >0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

Structure optimization based on natural products has become an effective way to develop new green fungicides. In this project, thirty-two novel NPs-derived hydrazide compounds were designed and synthesized by introducing the bioactive hydrazide substructure into sinapic acid and mycophenolic acid. The fungicidal bioassays indicated that the obtained hydrazide compounds showed excellent and selective fungicidal activity against specific pathogens, especially compounds C8 , D7 , and D8 with EC 50 values of 0.63, 0.56, and 0.43 μg mL -1 against M. oryzae , respectively. SAR indicated that the introduction of 4-fluoro, 4-chloro, and 2,4-difluoro groups was conducive to improving the fungicidal activity, while the extension of the hydrazide bridge would affect the selectivity for inhibitory activity. Subsequently, the effects of hydrazide compounds on rice seedling and zebrafish growth were also investigated. The fungicidal mechanism implied that treatment with compound B4 would cause significant changes in metabolites of plasma membrane-related linolenic acid metabolism, arachidonic acid metabolism, and α-linolenic acid metabolism pathways, which further led to the wrinkled hyphae and the blurred plasma membrane and cytoplasm. Finally, the frontier molecular orbitals and charge distribution were calculated to analyze the differences in bioactivity from a structural perspective. These results provide important guidance for the development and practical application of novel fungicides.

Background: Chlorsulfuron, metsulfuron-methyl and ethametsulfuron can damage sensitive crops in rotation pattern as a result of their long persistence in soil. To explore novel sulfonylurea (SU) herbicides with favorable soil degradation rates, four series of SUs were synthesized through a structure-based drug design (SBDD) strategy., Results: The target compounds, especially Ia, Id and Ie, exhibited prospective herbicidal activity against dicotyledon oil seed rape (Brassica campestris), amaranth (Amaranthus retroflexus), monocotyledon barnyard grass (Echinochloa crusgalli) and crab grass (Digitaria sanguinalis) at a concentration of 15 a.i. g ha -1 . Additionally, Ia, Id and Ig displayed excellent inhibitory effects against AtAHAS, with Kapp i values of 59.1, 34.5 and 71.8 μm, respectively, which were much lower than that of chlorsulfuron at 149.4 μm. The π-π stack and H-bonds between the Ia conformation and AtAHAS in the molecular docking results confirmed the series of compounds to be conventional AHAS inhibitors. In alkaline soil (pH = 8.46), compounds Ia-Ig revealed various degrees of acceleration in the degradation rate compared with chlorsulfuron. Besides, compound Ia showed considerable wheat and corn safety under postemergence at the concentration of 30, 60 and even 120 a.i. g ha -1 ., Conclusion: Overall, based on the synthetic procedure, herbicidal activity, soil degradation and crop safety, the Ia sulfonylureas series were chosen to be investigated as prospective AHAS inhibitors. The 5-dimethylamino group on SUs accelerated the degradation rate at different levels in alkaline soils which seems to be controllable in conventional cropping systems in their further application. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

A new series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. CPD is an inhibitor of ketol-acid reductoisomerase (KARI), an enzyme of the branched chain amino acid pathway in plants. The structures of CPD analogues were characterized by 1 H NMR and HRMS. The structure of N,N'-bis(4-(tert-butyl)phenyl)cyclopropane-1,1-dicarboxamide was further elucidated by X-ray diffraction. The herbicidal activities of these compounds were tested against lettuce (Lactuca sativa) and bentgrass (Agrostis stolonifera). Most of these compounds exhibited low herbicidal activity against both plant species. Among them, N,N'-bis(2-ethylphenyl)cyclopropane-1,1-dicarboxamide displayed moderate activity against bentgrass. Inhibition of KARI activity by the CPD analogues was also assessed experimentally and by molecular docking simulation with results supporting inhibition of KARI as their mode of action. These results provide the basis for design of more effective KARI inhibitors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Photodynamic therapy (PDT) is a robust cancer treatment modality, and the precise spatiotemporal control of its subcellular action site is crucial for its effectiveness. However, accurate comparison of the efficacy of different organelle-targeted PDT approaches is challenging since it is difficult to find a single system that can achieve separate targeting of different organelles with separable time windows and similar binding amounts. Herein, we conjugated chlorin e6 (Ce6) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (ammonium salt) (DSPE-PEG 5000 -NH 2 ) to afford DSPE-PEG-Ce6, which could migrate from mitochondrion to lysosome and ultimately to endoplasmic reticulum (ER) after cellular internalization. Benefiting from the dynamic subcellular distribution of DSPE-PEG-Ce6 with tunable organelle-binding amounts, we accurately determined the PDT efficacy order of the molecule, i.e., mitochondrion > ER > lysosome. This work proposes an ideal model system for accurately evaluating the specific organelle-targeted PDT efficacy and may promote the future development of effective PDT strategies., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sulfonylurea herbicides can lead to serious weed resistance due to their long degradation times and large-scale applications. This is especially true for chlorsulfuron, a widely used acetolactate synthase inhibitor used around the world. Its persistence in soil often affects the growth of crop seedlings in the following crop rotation, and leads to serious environmental pollution all over the world. Our research goal is to obtain chlorsulfuron-derived herbicides with high herbicidal activities, fast degradation times, as well as good crop safety. On account of the slow natural degradation of chlorsulfuron in alkaline soil, based on the previously reported results in acidic soil, the degradation behaviours of 5-substituted chlorsulfuron analogues ( L101 - L107 ) were investigated in a soil with pH 8.39. The experimental data indicated that 5-substituted chlorsulfuron compounds could accelerate degradation rates in alkaline soil, and thus, highlighted the potential for rational controllable degradation in soil. The degradation rates of these chlorsulfuron derivatives were accelerated by 1.84-77.22-fold, compared to chlorsulfuron, and exhibited excellent crop safety in wheat and corn (through pre-emergence treatment). In combination with bioassay activities, acidic and alkaline soil degradation, and crop safety, it was concluded that compounds L104 and L107 , with ethyl or methyl groups, are potential green sulfonylurea herbicides for pre-emergence treatment on wheat and corn. This paper provides a reference for the further design of new sulfonylurea herbicides with high herbicidal activity, fast, controllable degradation rates, and high crop safety.

Natural products are a source of many novel compounds with biological activity for the discovery of new pesticides and pharmaceuticals. Quinoxaline is a fused N -heterocycle in many natural products and synthetic compounds, and seven novel quinoxaline derivatives were designed and synthesized via three steps. Pesticidal activities of title quinoxaline derivatives were bioassayed. Most of these compounds had herbicidal, fungicidal, and insecticidal activities. The compounds 2-(6-methoxy-2-oxo-3-phenylquinoxalin-1(2 H )-yl)acetonitrile ( 3f ) and 1-allyl-6-methoxy-3-phenylquinoxalin-2(1 H )-one ( 3g ) were the most active herbicides and fungicides. Mode-of-action studies indicated that 3f is a protoprophyrinogen oxidase-inhibiting herbicide. Compound 3f also possessed broad-spectrum fungicidal activity against the plant pathogen Colletotrichum species. Some of these compounds also had insecticidal activity. Molecular docking and DFT analysis can potentially be used to design more active compounds.

Biological synthetic methods of nanoparticles have shown great advantages, such as environmental friendliness, low cost, mild reaction conditions, and enhanced biocompatibility and stability of products. Bacteria, as one of the most important living organisms, have been utilized as bioreducing nanofactories to biosynthesize many metal nanoparticles or compounds. Here, inspired by the disinfection process of KMnO 4 , we for the first time introduce bacteria as both the template and the reducing agent to construct a novel tumor microenvironment-responsive MnO x -based nanoplatform for biomedical applications in various aspects. It is found that the bacterium/MnO x -based nanospindles (EM NSs) can efficiently encapsulate the chemotherapeutic agent doxorubicin (DOX), leading to the fluorescence quenching of the drug. The as-formed DOX-loaded EM NSs (EMD NSs) are proven to be decomposed by glutathione (GSH) and can simultaneously release DOX and Mn 2+ ions. The former can be utilized for sensitive fluorescence-based GSH sensing with a limit of detection as low as 0.28  μ M and selective cancer therapy, while the latter plays important roles in GSH-activated magnetic resonance imaging and chemodynamic therapy. We also demonstrate that these nanospindles can generate oxygen in the presence of endogenous hydrogen peroxide to inhibit P-glycoprotein expression under hypoxia and can achieve excellent tumor eradication and tumor metastasis inhibition performance. Taken together, this work designs a multifunctional bacterially synthesized nanomissile for imaging-guided tumor-specific chemo-chemodynamic combination therapy and will have implications for the design of microorganism-derived smart nanomedicines., Competing Interests: The authors declare no competing financial interests., (Copyright © 2020 Yan-Wen Bao et al.)

Chlorsulfuron has been applied in wheat fields as a recognized herbicide worldwide, yet it was officially banned in China since 2014 for its soil persistence problem. On the basis of our previous research that 5-dimethylamino distinctively accelerated degradation rate in soils, a modified amino moiety ( Ia-c ) and monosubstituted amino group ( Id-e ) were introduced onto the fifth position of the benzene ring in sulfonylurea structures, as well as heterocyclic amino substituents ( If-g ) to seek a suitable soil degradation rate during such an in situ crop rotation system. Referring to the biological data and Sc AHAS inhibition and Sc AHAS docking results, they turned out to be AHAS inhibitors with high potent herbicidal activities. The various influence on soil degradation rate along with crop safety indicated that different substituents on the fifth position have exerted an apparent impact. Their united study of structure-activity-safety-degradation relationship has great potential to provide valuable information for further development of eco-friendly agrochemicals.

In order to develop a novel herbicide containing the β-triketone motif, a series of 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one derivatives were designed and synthesized. The bioassay results showed that compound II15 had good pre-emergent herbicidal activity even at a dosage of 187.5 g ha -1 . Moreover, compound II15 showed a broader spectrum of weed control when compared with a commercial herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), and displayed good crop safety to Triticum aestivum L. and Zea mays Linn. when applied at 375 g ha -1 under pre-emergence conditions, which indicated its great potential as a herbicide. More importantly, studying the molecular mode of action of compound II15 revealed that the novel triketone structure is a proherbicide of its corresponding phenoxyacetic acid auxin herbicide, which has a herbicidal mechanism similar to that of 2,4-D. The present work indicates that the 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one motif may be a potential lead structure for further development of novel auxin-type herbicides.

Red-emitting carbon dots (CDs) have attracted tremendous attention due to their wide applications in areas including imaging, sensing, drug delivery, and cancer therapy. However, it is still highly challenging for red-emitting CDs to simultaneously achieve high quantum yields (QYs), nucleus targeting, and super-resolution fluorescence imaging (especially the stimulated emission depletion (STED) imaging). Here, it is found that the addition of varied metal ions during the hydrothermal treatment of p -phenylenediamine (pPDA) leads to the formation of fluorescent CDs with emission wavelengths up to 700 nm. Strikingly, although metal ions play a crucial role in the synthesis of CDs with varied QYs, they are absent in the formed CDs, that is, the obtained CDs are metal-free, and the metal ions play a role similar to a "catalyst" during the CD formation. Besides, using pPDA and nickel ions (Ni 2+ ) as raw materials, we prepare Ni-pPCDs which have the highest QY and exhibit various excellent fluorescence properties including excitation-independent emission (at ∼605 nm), good photostability, polarity sensitivity, and ribonucleic acid responsiveness. In vitro and in vivo experiments demonstrate that Ni-pPCDs are highly biocompatible and can realize real-time, wash-free, and high-resolution imaging of cell nuclei and high-contrast imaging of tumor-bearing mice and zebrafish. In summary, the present work may hold great promise in the synthesis and applications of red emissive CDs.

Biofilm formation can lead to the treatment failure of persistent bacterial infections. Although a variety of antibacterial agents have been developed, the restricted drug penetration and the embedded bacteria's potentiated recalcitrance to these agents synergistically lead to the unsatisfactory anti-biofilm effect. Herein, we report the applications of metal-free quaternized carbon dots (CDs) in imaging and eliminating bacterial biofilms. The CDs prepared by the solvothermal treatment of dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (abbreviated as Si-QAC) and glycerol possess ultrasmall size (ca. 3.3 ± 0.4 nm) and strong positively charged (zeta potential: ca. +33.1 ± 2.5 mV) surfaces with long alkyl chain-linked quaternary ammonium groups. The small size of the CDs endows them with the penetration ability into the interior of Gram-negative and Gram-positive bacterial biofilms, which enables excellent fluorescence imaging of the biofilms. Due to the different surfaces of the two types of bacteria, the positively charged CDs selectively interact with the more negatively charged Gram-positive bacteria via electrostatic and hydrophobic interactions, which inactivates the Gram-positive bacteria and ultimately eradicates the Gram-positive bacterial biofilms. In addition, we synthesize a new type of quaternized CDs without long alkyl chains (termed TTPAC CDs), and validate that the long alkyl chains potentiate the hydrophobic adhesion between CDs and Gram-positive bacteria. Meanwhile, the crystal violet staining results reveal that the cationic CDs inhibit the formation of Gram-positive bacterial biofilms. Collectively, our work highlights the feasibility of using cationic and ultrasmall metal-free CDs to eliminate and inhibit Gram-positive bacterial biofilms, which represents a highly effective strategy to cope with refractory biofilm-associated infections.

Background: Anthranilic diamide insecticides control lepidopteran pests through selectively binding and activating insect ryanodine receptors. In order to search for potential insecticides targeting the ryanodine receptors, a series of anthranilic diamide analogs including trifluoromethyl, nitro, or chloro groups were designed and synthesized by the principle of bioisosterism and structural optimization., Results: Insecticidal data indicated that some compounds displayed good activity against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). In particular, the larvicidal activity of 6p against P. xylostella was 95% at 0.01 mg L -1 , equivalent to chlorantraniliprole (85%, 0.01 mg L -1 ). The comparative molecular similarity index analysis model obtained indicated that hydrogen bond acceptor and electron-withdrawing groups in the R' 3 group are favourable for insecticidal activity against M. separata, which is consistent with the structure-activity relationships. Moreover, the calcium imaging experiment indicated, like chlorantraniliprole, that 6h and 6p are interacting with the ryanodine receptor., Conclusion: Introducing trifluoromethyl, nitro, or chloro groups to a specific position in the N-phenylpyrazole could improve or maintain the activity against M. separata and P. xylostella. 6h and 6p could be used as potential lead compounds for ryanodine receptor modulators. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Lysosomal entrapment and liver accumulation are the two main obstacles faced by many anticancer drugs for achieving satisfactory therapeutic outcomes. Here, we develop a facile one-step hydrothermal synthetic route to prepare trace metal (M)-, N-, and O-doped carbon-dominated nanoparticles (termed as MNOCNPs, M = Ni, Pd, or Cu, metal content: <0.1 mol%) with exceptional photothermal properties (e.g., the ultrahigh extinction coefficient of 32.7 L g -1  cm -1 ), which can simultaneously realize preferable endoplasmic reticulum (ER) targeting and specific tumor enrichment without noticeable liver accumulation after poly(ethylene glycol) (PEG) conjugation. More interestingly, the PEG-modified MNOCNPs with nanoscale lengths exhibit considerable nucleolar delivery and increased tumor accumulation upon laser irradiation. After fluorescence labeling, these PEG-modified MNOCNPs are suitable for fluorescence/photoacoustic/thermal triple-modal imaging-guided photothermal cancer treatment. Additionally, the ultralow metal content ensures the exceptional biosafety of the nanoagents. The present work provides a novel, facile, and general synthetic method of carbon-dominated nanoparticles with superior photothermal properties for highly efficient tumor ablation, and the large-organelle (ER and nucleus)-targeted cancer therapeutic strategy may represent an alternative solution for optimizing the anticancer efficacy of nanomaterials. STATEMENT OF SIGNIFICANCE: Limited wire-like nanomaterials have been used for biomedical applications due to their lack of intrinsic photothermal properties, poor cellular uptake and tumor accumulation, and potential biotoxicity arising from their micrometer lengths and/or massive heavy metal doping. Besides, the clinical applications of many nanoagents are hindered by their tendency to accumulate in liver, which may cause severe liver toxicity. Herein, we develop for the first time a one-step hydrothermal method to prepare wire-like trace metal-, N-, and O-doped carbon-dominated nanoparticles with excellent photothermal properties, massive cellular uptake, preferable ER localization, selective tumor targeting with negligible liver deposition, laser irradiation-enhanced nucleolar delivery and tumor accumulation, and multimodal imaging-guided cancer therapy. This work opens a new window for simultaneously overcoming lysosomal entrapment and liver accumulation in cancer therapy., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Nanomaterial-based enzyme mimics (nanozymes) are attracting increasing attention because of their low production cost, high stability against denaturation, and resistance to high concentrations of substrates. Here, carbon nanoparticles doped with a small amount (<5 mol%) of Pt (denoted as PtCNPs) are synthesized via a facile, cost-effective hydrothermal treatment of p-phenylenediamine (PPD) and K 2 PtCl 4 . The obtained PtCNPs possess high aqueous stability, excellent water-dispersibility, and suitable size (∼15 nm). More interestingly, the PtCNPs exhibit an intrinsic peroxidase-like activity that can quickly catalyze 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H 2 O 2 ) and produce a blue color. Importantly, since satisfactory catalytic properties were also observed when K 2 PtCl 4 was replaced with CuCl 2 , NiCl 2 , or Na 2 PdCl 4 during the synthesis, the PPD- and inorganic metal salt-involved hydrothermal synthetic approach may be developed as a general and simple way to fabricate new nanozymes. Besides, the steady-state kinetics reveals that the PtCNPs have a stronger affinity for TMB and a weaker affinity for H 2 O 2 compared with horseradish peroxidase. On the basis of the color reaction, a colorimetric detection method for H 2 O 2 and glucose has been successfully established with a detection limit of 0.15 and 0.30 μM, respectively. Further, the method has also been successfully applied for glucose detection in human serum samples. To sum up, this work develops a new synthetic method of metal-doped carbon nanomaterials and demonstrates their capability for the sensitive and selective detection of H 2 O 2 and glucose, which may foster the development of new nanozymes for biosensing applications.

Integration of multiple diagnostic/therapeutic modalities into a single system with ultrasmall size, excellent photothermal/photodynamic properties, high cellular uptake efficiency, nuclear delivery capacity, rapid renal clearance, and good biosafety is highly desirable for cancer theranostics, but still remains challenging. Here, a novel type of multifunctional nanodots (denoted as BCCGH) was synthesized by mixing bovine serum albumin, carbon dots, and metal ions (Cu 2+ and Gd 3+ ), followed by the conjugation with a photosensitizer (HPPH). The nanodots hold great promise for fluorescence/photoacoustic/magnetic resonance/photothermal imaging-guided synergistic photothermal/photodynamic therapy (PDT) because of their appealing properties such as high photothermal conversion efficiency (68.4%), high longitudinal relaxivity (11.84 mM -1 s -1 , 7 T), and superior colloidal stability with negligible Gd 3+ release. Benefiting from the massive cellular uptake, endoplasmic reticulum/mitochondrion-targeting ability, and mild near-infrared laser irradiation-promoted nuclear delivery of BCCGH, a high anticancer therapeutic efficiency is achieved in the subsequent in vitro PDT. Besides, as revealed by the in vivo/ex vivo results, the nanodots also exhibit excellent tumor accumulation, efficient renal clearance, complete tumor ablation, and exceptional biosafety. To summarize, this work develops a carbon dot-mediated and albumin-based synthetic approach for constructing ultrasmall and multifunctional nanodots, which may hold great potential for cancer theranostics and beyond.

Tumor growth and metastasis are two main causes of cancer-related deaths. Here, we simultaneously investigated the effects of nanoparticles on cancer cell viability and migration using polyethylene glycol (PEG)-modified, platinum-doped (<4 mol %) carbon nanoparticles (denoted as PEG-PtCNPs). The bare PtCNPs were prepared by the facile one-step hydrothermal treatment of p-phenylenediamine and K 2 PtCl 4 in aqueous solution. After PEGylation, the obtained PEG-PtCNPs can serve as an excellent photothermal nanoagent for cell migration inhibition, laser-triggered nuclear delivery, effective tumor accumulation, and imaging-guided tumor ablation with improved therapeutic efficacy and reduced side effects. In the absence of laser exposure, the positively charged PEG-PtCNPs with a hydrodynamic diameter of ∼19 nm easily entered the cells by endocytosis and were located in multiple organelles (including mitochondrion, endoplasmic reticulum, lysosome, and Golgi apparatus), causing a slight increase in the expression level of nuclear protein lamin A/C. Upon mild laser irradiation (0.3 W cm -2 ), the fragmented cytoskeletal structures and overexpression of lamin A/C were observed, thus inhibiting cancer cell migration. Furthermore, hyperthermia induced by PEG-PtCNPs plus laser irradiation at a higher power density (1.0 W cm -2 ) could cause irreversible damage to the nuclear membranes and then facilitate the nuclear delivery of the nanoagents without the introduction of nuclear targeting ligands. Taken together, this work develops a facile synthetic approach of platinum-based carbon nanoparticles with excellent photothermal properties, and demonstrates their potential applications for modulating tumor metastasis and realizing multi-organelle-targeted tumor ablation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Nucleolus tracking and nucleus-targeted photodynamic therapy are attracting increasing attention due to the importance of nucleolus and the sensitivity of nucleus to various therapeutic stimuli. Herein, a new class of multifunctional fluorescent carbon quantum dots (or carbon dots, CDs) synthesized via the one-pot hydrothermal reaction of m-phenylenediamine and l-cysteine was reported to effectively target nucleolus. The as-prepared CDs possess superior properties, such as low-cost and facile synthesis, good water dispersibility, various surface groups for further modifications, prominent photostability, excellent compatibility, and rapid/convenient/wash-free staining procedures. Besides, as compared with SYTO RNASelect (a commonly used commercial dye for nucleolus imaging) that can only image nucleolus in fixed cells, the CDs can realize high-quality nucleolus imaging in not only fixed cells but also living cells, allowing the real-time tracking of nucleolus-related biological behaviors. Furthermore, after conjugating with protoporphyrin IX (PpIX), a commonly used photosensitizer, the resultant CD-PpIX nanomissiles showed remarkably increased cellular uptake and nucleus-targeting properties and achieved greatly enhanced phototherapeutic efficiency because the nuclei show poor tolerance to reactive oxygen species produced during the photodynamic therapy. The in vivo experiments revealed that the negatively charged CD-PpIX nanomissiles could rapidly and specifically target a tumor site after intravenous injection and cause efficient tumor ablation with no toxic side effects after laser irradiation. It is believed that the present CD-based nanosystem will hold great potential in nucleolus imaging and nucleus-targeted drug delivery and cancer therapy.

Copper-containing nanomaterials have been applied in various fields because of their appealing physical, chemical, and biomedical properties/functions. Herein, for the first time, a facile, room-temperature, and one-pot method of simply mixing copper ions and sulfur-doped carbon dots (CDs) is developed for the synthesis of copper/carbon quantum dot (or CD)-crosslinked nanosheets (CuCD NSs). The thus-obtained CuCD NSs with the size of 20-30 nm had a high photothermal conversion efficiency of 41.3% and good photothermal stability. Especially, after coating with thiol-polyethylene glycol and fluorescent molecules, the resultant CuCD NSs could selectively target tumor tissues and realize multimodal (photoacoustic, photothermal, and fluorescence) imaging-guided cancer therapy. More importantly, our CuCD NSs exhibited laser-triggered cytosolic delivery, lysosomal escape, and nuclear-targeting properties, which greatly enhanced their therapeutic efficacy. The significantly enhanced tumor accumulation of CuCD NSs after in situ tumor-site laser irradiation was also observed in in vivo experiments. These in vitro and in vivo events occurring during the continuous laser irradiation have not been observed. Overall, this work develops a CD-assisted synthetic method of photothermal nanoagents for triple-modal imaging-guided phototherapy and deepens our understanding of the action mechanism of photothermal therapy, which will promote the development of nanomedicine and beyond.

The degradation issue of sulfonylurea (SU) has become one of the biggest challenges that hamper the development and application of this class of herbicides, especially in the alkaline soils of northern China. On the basis of the previous discovery that some substituents on the fifth position of the benzene ring in Chlorsulfuron could hasten its degradation rate, apparently in acidic soil, this work on Metsulfuron-methyl showed more convincing results. Two novel compounds (I-1 and I-2) were designed and synthesized, and they still retained potent herbicidal activity in tests against both dicotyledons and monocotyledons. The half-lives of degradation (DT 50 ) assay revealed that I-1 showed an accelerated degradation rate in acidic soil (pH 5.59). Moreover, we delighted to find that the degradation rate of I-1 was 9-10-fold faster than that of Metsulfuron-methyl and Chlorsulfuron when in alkaline soil (pH 8.46), which has more practical value. This research suggests that a modified structure that has potent herbicidal activity as well as accelerated degradation rate could be realized and this approach may provide a way to improve the residue problem of SUs in farmlands with alkaline soil.

We prepare for the first time a novel type of fluorescent carbon quantum dot (or carbon dot, CD) with intrinsic mitochondrial targeting ability by a one-step hydrothermal treatment of chitosan, ethylenediamine and mercaptosuccinic acid. The as-prepared CDs can realize mitochondrial imaging and mitochondria-targeted photodynamic cancer therapy without further modifications of other mitochondriotropic ligands (such as triphenylphosphine, TPP). Currently, many commercial mitochondrial probes suffer from the lack of modifiable groups, poor photostability, short tracking time, high cost and/or complicated staining procedures, which severely limit their applications in live-cell mitochondrial imaging. Compared to commercial mitochondrial probes such as MitoTrackers, our CDs exhibit remarkable features including ultra-simple and cost-effective synthesis, excellent photostability, facile storage, easy surface modification, wash-free and long-term imaging capability and negligible cytotoxicity. Besides, since mitochondria are susceptible to the reactive oxygen species generated during chemo-, photo- or radiotherapy, mitochondria-targeted cancer therapy has attracted much attention due to its satisfying anticancer efficiency. To test if the CDs can be used for mitochondria-targeted drug delivery, they were conjugated with a photosensitizer rose bengal (RB) and the resultant CDs-RB nanomissiles achieved efficient cellular uptake and mitochondrial targeting/accumulation, realizing mitochondria-targeted photodynamic therapy. We believe that the CD-based nanotheranostics holds great promise in various biomedical applications.

Microbial viability assessment plays a key role in many areas such as pathogen detection, infectious disease treatment and antimicrobial drug development. Many conventional viability dyes (such as propidium iodide, PI) used for differentiating live/dead microbes suffer from notable cytotoxicity, poor photostability and are of high cost. Thus their applications for accurate microbial viability determination are limited. Herein, for the first time we report the successful synthesis of fluorescent carbon dots (CDs) from bacteria via one-step hydrothermal carbonization. Benefiting from their highly negative surface charge (the zeta potential is as high as around -42 mV) and suitable size, the CDs can selectively stain dead microbial cells (bacteria and fungi) but not live ones. Importantly, compared to the widely used commercial dye PI, the developed CDs possess many great advantages including low cytotoxicity, multicolor imaging ability, excellent photostability and high selectivity. Moreover, because the synthetic method is simple, inexpensive and eco-friendly, this type of CD is suitable for large-scale production, making it an excellent candidate for microbial live/dead differentiation and viability assessment. The present work explores the feasibility of using bacteria to fabricate novel CDs and broadens the applications of CDs for biomedical applications.

Background: To develop a coumarin-based fungicide, a series of 3-benzoyl-4-hydroxylcoumarin derivatives were synthesised and their fungicidal activities were evaluated against typical fungi occurring in Chinese agroecosystems., Results: Target compounds were characterised through (1) H NMR, (13) C NMR and high-resolution mass spectrometry. The crystal structure of compound III-21 was determined through X-ray diffraction. Bioassay results indicated that most of the target compounds showed good growth inhibition against all of the fungi tested in vitro. EC50 of the target compounds against Physalospora piricola, Rhizoctonia cerealis, Sclerotinia sclerotiorum and Botrytis cinerea indicated that most of the target compounds displayed comparable activity with that of carbindazim and chlorothalonil in vitro. Among these compounds, the analogue 3-(2-bromo-4-chlorobenzoyl)-4-hydroxylcoumarin (III-21) displayed the optimum growth inhibition against R. cerealis (87.5%) and B. cinerea (82.7%) in vivo at 200 µg mL(-1) concentration; thus, this analogue is a potential inhibitor of pathogenic fungi and a new major compound for further optimisation. The results of analysing the structure-activity relationships demonstrated that changes in substituents on benzene ring A of 3-benzoyl-4-hydroxylcoumarin caused different fungicidal activities and provided original information on the preferential conformation to maintain high activities., Conclusion: The present work demonstrated that 3-benzoyl-4-hydroxylcoumarin derivatives can be used as possible major compounds to develop novel fungicides. © 2015 Society of Chemical Industry., (© 2015 Society of Chemical Industry.)

An efficient synthesis of dihydrobenzo[c]phenanthridinones was achieved by utilizing an indium(0)-mediated intramolecular cyclization reaction under ligand- and base-free conditions. A variety of functional groups were tolerated in the present protocol.

Because of the distinct surface structures of different cells (mammalian cells, fungi, and bacteria), surface labeling for these cells requires a variety of fluorescent dyes. Besides, fluorescent dyes (especially the commercial ones) for staining Gram-negative bacterial cell walls are still lacking. Herein, a conformation-adjustable glycol chitosan (GC) derivative (GC-PEG cholesterol-FITC) with "all-in-one" property was developed to realize universal imaging for plasma membranes of mammalian cells (via hydrophobic interaction) and cell walls of fungal and bacterial cells (via electrostatic interaction). By comparing the different staining behaviors of GC-PEG cholesterol-FITC and three other analogs (GC-PEG-FITC, GC-FITC, and cholesterol-PEG-FITC), we have elucidated the different roles the hydrophobic and electrostatic interactions play in the staining performance of these different cells. Such a simple, noncytotoxic, economic, and universal cell surface staining reagent will be very useful for investigating cell surface-related biological events and advancing cell surface engineering of various types of cells.

To discover potent insecticides targeting ryanodine receptors (RyRs), a series of novel anthranilic diamides analogues (12a-12u) containing N-substituted phenylpyrazole were designed and synthesized. These compounds were characterized by (1)H NMR, (13)C NMR, and HRMS, and the structure of compound 12u was confirmed by X-ray diffraction. Their insecticidal activities indicated that these compounds displayed moderate to excellent activities. In particular, 12i showed 100 and 37% larvicidal activities against oriental armyworm (Mythimna separata) at 0.25 and 0.05 mg L(-1), equivalent to that of chlorantraniliprole (100%, 0.25 mg L(-1); and 33%, 0.05 mg L(-1)). The activity of 12i against diamondback moth (Plutella xylostella) was 95% at 0.05 mg L(-1), whereas the control was 100% at 0.05 mg L(-1). The calcium-imaging technique experiment results showed that the effects of 12i on the intracellular calcium ion concentration ([Ca(2+)]i) in neurons were concentration-dependent. After the central neurons of Helicoverpa armigera were dyed by loading with fluo-5N and treated with 12i, the free calcium released in endoplasmic reticulum indicated the target of compound 12i is RyRs or IP3Rs. The activation of RyRs by natural ryanodine completely blocked the calcium release induced by 12i, which indicated that RyRs in the central neurons of H. armigera third-instar larvae is the possible target of compound 12i.

Efficient cellular uptake of nanoparticles is crucial for modulating the cell behaviors as well as dictating the cell fate. In this work, by using two commercial reagents (the membrane modification reagent "cholesterol-PEG-biotin" and the avidin-modified quantum dots (QDs) "QD-avidin"), we achieved the enhanced plasma membrane enrichment and endocytosis of fluorescent QDs in cancer cells through cell surface engineering. The QD-cell interaction involved two stages: adsorption and internalization. After incubation with cholesterol-PEG2k-biotin, the cell membrane was engineered with biotin groups that would actively recruit QD-avidin to the cell surface within 1 min. This fast adsorption process could realize high quality and photostable plasma membrane imaging, which is simple, low-cost and generally applicable as compared with the previously reported membrane protein/receptor labeling-based QD imaging. After that, the QDs attached on the cell surface underwent the internalization process and 12 h later, almost all the QDs were internalized through endocytosis. Notably, we found that the internalization of QDs was not via common endocytosis pathways (such as clathrin- or caveolae-mediated endocytosis or macropinocytosis) but more likely via lipid raft-dependent endocytosis. In contrast, without cell surface engineering, the QD-avidin showed negligible cellular uptake. The results demonstrate that cell surface engineering is an efficient strategy to image the plasma membrane and increase cellular uptake of nanoparticles, and will be potentially applied to enhance the efficacy of nanomedicines when therapeutic nanoparticles are used.

A series of (2-benzoylethen-1-ol)-containing benzothiazine derivatives was synthesized, and their herbicidal activities were first evaluated. The bioassay results indicated that some of 3-benzoyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide derivatives displayed good herbicidal activity in greenhouse testing, especially, compound 4w had good pre-emergent herbicidal activities against Brassica campestris, Amaranthus retroflexus and Echinochloa crusgalli even at a dosage of 187.5 g ha(-1). More importantly, compound 4w displayed significant inhibitory activity against Arabidopsis thaliana HPPD and was identified as the most potent candidate with IC50 value of 0.48 μM, which is better than the commercial herbicide sulctrione (IC50=0.53 μM) and comparable with the commercial herbicide mesotrione (IC50=0.25 μM). The structure-activity relationships was studied and provided some useful information for improving herbicidal activity. The present work indicated that (2-benzoylethen-1-ol)-containing 1,2-benzothiazine motif could be a potential lead structure for further development of novel HPPD inhibiting-based herbicides., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: To explore the potential of contrast-enhanced computed tomography (CECT) using ExiTron nano6000 for assessment of liver lesions in mouse models., Methods: Three mouse models of liver lesions were used: bile duct ligation (BDL), lipopolysaccharide (LPS)/D-galactosamine (D-GalN), and alcohol. After injection with the contrast agent ExiTron nano6000, the mice were scanned with micro-CT. Liver lesions were evaluated using CECT images, hematoxylin and eosin staining, and serum aminotransferase levels. Macrophage distribution in the injury models was shown by immunohistochemical staining of CD68. The in vitro studies measured the densities of RAW264.7 under different conditions by CECT., Results: In the in vitro studies, CECT provided specific and strong contrast enhancement of liver in mice. CECT could present heterogeneous images and densities of injured livers induced by BDL, LPS/D-GalN, and alcohol. The liver histology and immunochemistry of CD68 demonstrated that both dilated biliary tracts and necrosis in the injured livers could lead to the heterogeneous distribution of macrophages. The in vitro study showed that the RAW264.7 cell masses had higher densities after LPS activation., Conclusion: Micro-CT with the contrast agent ExiTron nano6000 is feasible for detecting various liver lesions by emphasizing the heterogeneous textures and densities of CECT images.

Aim: To determine the risk factors for new-onset diabetes mellitus (NODM) after liver transplantation by conducting a systematic review and meta-analysis., Methods: We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data. Discrepancies were resolved in consultation with a third reviewer. All statistical analyses were performed with the RevMan5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated using either a fixed effects or a random effects model, based on the presence (I (2) < 50%) or absence (I (2) > 50%) of significant heterogeneity., Results: Twenty studies with 4580 patients were included in the meta-analysis, all of which were retrospective. The meta-analysis identified the following significant risk factors: hepatitis C virus (HCV) infection (OR = 2.68; 95%CI: 1.92-3.72); a family history of diabetes (OR = 1.69, 95%CI: 1.09-2.63, P < 0.00001); male gender (OR = 1.53; 95%CI: 1.24-1.90; P < 0.0001); impaired fasting glucose (IFG; OR = 3.27; 95%CI: 1.84-5.81; P < 0.0001); a family history of diabetes (OR = 1.69; 95%CI: 1.09-2.63; P = 0.02); use of tacrolimus (OR = 1.34; 95%CI: 1.03-1.76; P = 0.03) and body mass index (BMI)(WMD = 1.19, 95%CI: 0.69-1.68, P < 0.00001). Other factors, such as hepatitis B virus infection and alcoholism, were not found to be associated with the incidence of NODM., Conclusion: The study showed that HCV infection, IFG, a family history of diabetes, male gender, tacrolimus and BMI are risk factors for NODM after liver transplantation.

Copper-based nanomaterials have broad applications in electronics, catalysts, solar energy conversion, antibiotics, tissue imaging, and photothermal cancer therapy. However, it is challenging to prepare ultrasmall and ultrastable CuS nanoclusters (NCs) at room temperature. In this article, a simple method to synthesize water-soluble, monodispersed CuS NCs is reported based on the strategy of trapping the reaction intermediate using thiol-terminated, alkyl-containing short-chain poly(ethylene glycol)s (HS-(CH2)11-(OCH2CH2)6-OH, abbreviated as MUH). The MUH-coated CuS NCs have superior stability in solutions with varied pH values and are stable in pure water for at least 10 months. The as-prepared CuS NCs were highly toxic to A549 cancer cells at a concentration of higher than 100 μM (9.6 μg/mL), making them be potentially applicable as anticancer drugs via intravenous administration by liposomal encapsulation or by direct intratumoral injection. Besides, for the first time, CuS NCs were used for antibacterial application, and 800 μM (76.8 μg/mL) CuS NCs could completely kill the E. coli cells through damaging the cell walls. Moreover, the NCs synthesized here have strong near-infrared (NIR) absorption and can be used as a candidate reagent for photothermal therapy and photoacoustic imaging. The method of trapping the reaction intermediate for simple and controlled synthesis of nanoclusters is generally applicable and can be widely used to synthesize many metal-based (such as Pt, Pd, Au, and Ag) nanoclusters and nanocrystals.

Orthotopic liver transplantation is currently the best treatment option for selected patients with hepatocellular carcinoma (HCC). From 1980 to 2011, 8874 patients with HCC in China underwent liver transplantation. The organ donation classification criteria of China (China criteria), which are established by the Government of China, are divided into three parts: China criteria I, donation after brain death; China criteria II, donation after cardiac death and China criteria III, donation after dual brain-cardiac death. Data from the China Liver Transplant Registry(CLTR) System shows that patients within the Milan criteria have higher survival rates than those who are beyond these criteria. Based on CLTR data, altogether 416 patients received living-donor liver transplantation(LDLT) in China. Their 1-year and 3-year survival rates were significantly higher than those of the non-LDLT recipients. The most common early stage(<30 days after liver transplantation) complications include pleural effusion, diabetes, peritoneal effusion or abscess, postoperative infection, hypertension and intraperitoneal hemorrhage; while the most common late stage (≥ 30 days after liver transplantation) complications were diabetes, hypertension, biliary complications,postoperative infection, tacrolimus toxicity and chronic graft rejection. The incidence of vascular complication, which is the main reason for acute graft failure and re-transplantation, was 2.4%. Liver transplantation is an effective treatment for patients with HCC in China.

To identify the disease-causing gene for a large multi-generational Chinese family affected by familial hypertrophic cardiomyopathy (FHCM), genome-wide screening was carried out in a Chinese family with FHCM using micro-satellite markers, and linkage analysis was performed using the MLINK program. The disease locus was mapped to 1q32 in this family. Screening for a mutation in the cardiac troponin T (cTnT) gene was performed by a PCR and sequencing was done with an ABI Prism 3700 sequencer. A novel C-->G transition located in the ninth exon of the cTnT gene, leading to a predicted amino acid residue change from Ile to Met at codon 90, was identified in all individuals with hypertrophic cardiomyopathy (HCM). The results presented here strongly suggest that Ile90Met, a novel mutation in the cTnT gene, is causative agent of HCM in this family.