Electro-absorption modulated 53 Gbps widely tunable laser based on half-wave V-coupled cavities.

In this paper, a 53 Gbps widely tunable transmitter is experimentally demonstrated for the first time, to our knowledge. An InGaAlAs/InP multiple-quantum-well (MQW) wafer is used with an identical layer structure for both the V-coupled cavity laser (VCL) and the electro-absorption modulator (EAM). The VCL uses a shallow-etched waveguide to reduce loss, while the EAM uses a deep-etched waveguide to increase the 3-dB modulation bandwidth. With the temperature varying from 19.5 to 30°C, the transmitter achieves wavelength tuning of 42 channels with a spacing of 100 GHz, corresponding to a tuning range of 32.6 nm from 1538.94 to 1571.54 nm. The static extinction ratio (ER) for all channels is higher than 14 dB. The measured 3-dB electro-optic (E0) bandwidth of the transmitter is over 40 GHz, which fits well with the calculated 3-dB bandwidth. At a fixed peak-to-peak driving voltage of 2.4 V, all channels exhibit clearly an open eye diagram with a 53 Gbps non-return-to-zero (NRZ) signal, while the dynamic ER is higher than 4.5 dB.

Visible-light organophotoredox-mediated intermolecular formal [4 + 2] cycloadditions of arylcyclobutylamines with olefins.

We have developed a visible-light-mediated formal [4 + 2] cycloaddition of arylcyclobutylamines with olefins, using QXPT-NPhCN as an organic photocatalyst. The corresponding cycloadducts could be obtained from electron-deficient olefins, aryl olefins and exocyclic olefins. We found that the addition of K3PO4 could significantly promote the cycloadditions. Using this method, 2-functionalized cyclohexylamines including the ones with spiro-skeletons can be expediently obtained. Based on the "3D-bioisostere" principle, we designed and synthesized three cyclohexylamine 2-sulfonylurea compounds.

Visible-Light Organophotoredox-Mediated [3 + 2] Cycloaddition of Arylcyclopropylamine with Structurally Diverse Olefins for the Construction of Cyclopentylamines and Spiro[4.n] Skeletons.

We developed a visible-light-mediated [3 + 2] cycloaddition of arylcyclopropylamine with structurally diverse olefins using QXPT-NPh as a highly efficient organic photoredox catalyst. We first achieved the use of various alkyl-substituted alkenes in intermolecular [3 + 2] cycloadditions with cyclopropylamine. We also developed a general and efficient strategy for the construction of structurally diverse cyclopentane-based spiro[4.n] skeletons with 1,3-difunctional groups, which broadly exist in natural products and synthetic molecules. Furthermore, we proposed a hydrogen-bond mode between the arylcyclopropylamine and the photocatalyst QXPT-NPh.

Cellular transport of uranium and its cytotoxicity effects on CHO-k1 cells.

Uranium is a radioactive heavy metal and a significant public health concern; however, its associated underlying toxicological mechanisms remain largely unknown. In this work, the uptake and efflux processes of uranium in CHO-k1 cells were studied and the cytotoxicity effects were explored. It was found that both the uptake and efflux processes took place rapidly and half of the internalized uranium was expelled within 8 h. The uranium exposure caused a decrease of cell viability and adhesion ability in a dose-dependent manner and blocked the cell cycle at the G1 stage. In addition, gene expression analysis revealed relative changes in the transcription of metabolism related genes. Further studies revealed that the cytotoxicity of uranium could be alleviated by exposing cells to a lower temperature or by the addition of amantadine-HCl, an endocytosis inhibitor. Interestingly, after uranium exposure, needle-like precipitates were observed in both intracellular and extracellular regions. These findings collectively suggest that the cellular transport of uranium is a rapid process that disturbs cell metabolism and induces cytotoxicity, and this impact could be reduced by slowing down endocytic processes.

Chemical preparation, degradation analysis, computational docking and biological activities of novel sulfonylureas with 2,5-disubstituted groups.

Based on the previous finding that a substitution at 5-position of the benzene ring is favorable to enhance the degradation rates of sulfonylurea herbicides, a total of 16 novel 2,5-disubsituted sulfonylurea compounds were chemically synthesized and fully characterized by means of 1H NMR, 13C NMR, HRMS and X-ray diffraction. By using HPLC analysis, the degradation behavior of M03, a compound belonging to this family, was studied and confirmed that chlorsulfuron itself is not a degraded product of the 2,5-disubstituted sulfonylureas. Inhibition constants against plant acetohydroxyacid synthase (AHAS) were determined for selected compounds, among which SU3 showed seven times stronger activity against the mutant W574L enzyme than chlorsulfuron. Molecular docking suggested that the substituted group at 5-position of benzene ring is likely to interact with the surrounding residues Met200 and Asp376 of AtAHAS. From the greenhouse herbicidal assay and crop safety test, SU5 and SU6 are considered as herbicide candidates to control dicotyledon weeds in corn, while SU3 is likely to be a promising candidate to control dicotyledon weed species and barnyard grass in wheat. The present research has therefore provided some new insights to understand the structure-activity relationships of herbicidal sulfonylureas with di-substitutions at benzene ring.

Alkaline Soil Degradation and Crop Safety of 5-Substituted Chlorsulfuron Derivatives.

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.

Synthesis, Herbicidal Activity, Crop Safety and Soil Degradation of Pyrimidine- and Triazine-Substituted Chlorsulfuron Derivatives.

Chlrosulfuron, a classical sulfonylurea herbicide that exhibits good safety for wheat but causes a certain degree of damage to subsequent corn in a wheat-corn rotation mode, has been suspended field application in China since 2014. Our previous study found that diethylamino-substituted chlorsulfuron derivatives accelerated the degradation rate in soil. In order to obtain sulfonylurea herbicides with good crop safety for both wheat and corn, while maintaining high herbicidal activities, a series of pyrimidine- and triazine-based diethylamino-substituted chlorsulfuron derivatives (W102-W111) were systematically evaluated. The structures of the synthesized compounds were confirmed with 1H NMR, 13C NMR, and HRMS. The preliminary biological assay results indicate that the 4,6-disubstituted pyrimidine and triazine derivatives could maintain high herbicidal activity. It was found that the synthesized compounds could accelerate degradation rates, both in acidic and alkaline soil. Especially, in alkaline soil, the degradation rate of the target compounds accelerated more than 22-fold compared to chlorsulfuron. Moreover, most chlorsulfuron analogs exhibited good crop safety for both wheat and corn at high dosages. This study provided a reference for the further design of new sulfonylurea herbicides with high herbicidal activity, fast degradation rates, and high crop safety.

Antimicrobial Activity of Natural Plant Compound Carvacrol Against Soft Rot Disease Agent Dickeya zeae.

Dickeya zeae is a globally important bacterial pathogen that has been reported to cause severe soft rot diseases in several essential food crops, including bananas, rice, maize, and potatoes. Carvacrol, a hydrophobic terpene component, is found in aromatic plants of the Labiatae family and various essential oils. However, little work has been done on its antimicrobial potential against D. zeae. This study aimed to evaluate the antimicrobial activity and the functional mechanism of carvacrol against D. zeae. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of carvacrol against D. zeae were 0.1 mg/mL and 0.2 mg/mL, respectively. Carvacrol affected the cell membrane of D. zeae, as revealed by decreased intracellular ATP concentration, nucleic acid leakage, and decreased membrane potential. Scanning electron microscopy (SEM) micrographs confirmed that D. zeae cell membranes were damaged by carvacrol. Furthermore, a significant inhibition of D. zeae swimming motility and biofilm formation was observed following treatments with carvacrol at sub-inhibitory concentrations, indicating a significantly negative effect on these virulence factors. Accordingly, the tissue infection test revealed that carvacrol significantly reduced the pathogenicity of D. zeae. In a pot experiment, inoculated banana seedlings displayed remarkably lesser disease symptoms following treatment with carvacrol, and the control efficiency for banana soft rot was 32.0% at 14 days post-inoculation. To summarize, carvacrol exhibits strong antimicrobial activity against D. zeae and great potential applications in the control of D. zeae-associated crop diseases.

ICP-MS based on-line monitoring of Pu-239 airborne concentration.

An online monitoring technology of Pu-239 aerosol based on aerosol direct introduction device, membrane desolvation nebuliser and ICP-MS was established for workplaces of reprocessing plants. Briefly, 0.8 l min-1 Pu-239 aerosol from the workplace was introduced into the aerosol direct introduction device where the air was replaced by Argon, and then the aerosol was introduced into the ICP-MS for measurement. To determine the activity of Pu-239 aerosol, 1.10E-3 Bq ml-1 Pu-242 standard solution generated by a membrane desolvation nebuliser was used. The introduction efficiency of the nebuliser was determined by sampling the aerosol generated from the nebuliser with Lead Standard Solution by glass fiber filter, which was (26.82 ± 3.33) %. The mass bias between Pu-239 and Pu-242 for the ICP-MS measurement was determined by Pu-239 and Pu-242 standard solutions generated by the nebuliser, and mass discrimination correction factor for Pu-239/Pu-242 was 0.972 ± 0.010. The limit of detection (LOD) and limit of quantification (LOQ) of this system were calculated according to the ISO 20 899:2018, which were 2.24E-05 Bq m-3 and 7.45E-05 Bq m-3 with 1 min measurement. The main interference which was from U-238 was determined by U-238 standard solution generated by the nebuliser, and the interferences of U-238 to 239 was (8.50 ± 1.05) E-05. According to the counts of U-238 from several workplaces of reprocessing plant where this system was tested, 239 counts rate from the interferences of U-238 of those workplaces were at the same level of the system background counts, which meant that the LOD above was suitable for those places.

In Vitro Formation of Dickeya zeae MS1 Biofilm.

Bacterial soft rot caused by Dickeya zeae MS1 (Erwinia chrysanthemi) is one of the most devastating banana diseases worldwide. However, knowledge of the development and ecological interactions of D. zeae MS1 biofilm is limited. Here, we visualized the development and architecture of D. zeae MS1 biofilm using confocal laser scanning microscopy, and we evaluated the ability of D. zeae MS1 to form biofilms under different environmental conditions (carbon sources, temperatures, pH levels and mineral elements) using a microtiter plate assay. We found that the development of D. zeae MS1 biofilm could be categorized into four phases and that mature biofilm consisted of a highly organized architecture of both bacterial cells and a self-produced matrix of extracellular polysaccharides. Furthermore, sucrose was the most suitable carbon source for supporting the growth of biofilm cells and that 32 °C and pH 7.0 were the most favorable of the temperatures and pH levels examined. Meanwhile, the addition of Ca2+, Fe2+, K+ and Na+ enhanced the formation of biofilm in minimal medium cultures, whereas 2.5 mM Cu2+ and Mn2+ was inhibitory. A better understanding of biofilm formation under different environmental parameters will improve our knowledge of the growth kinetics of D. zeae MS1 biofilm.

Lewis Acid-Catalyzed Intramolecular [3+2] Cross-Cycloaddition of Aziridine 2,2-Diesters with Conjugated Dienes for Construction of Aza-[n.2.1] Skeletons.

A novel Lewis acid-catalyzed [3+2] intramolecular cross-cycloaddition (IMCC) between aziridine 2,2-diesters and conjugated dienes has been developed. This is the first regiospecific IMCC of intramolecular 1,3-dipolar cycloadditions of azomethine ylides with carbon=carbon double bonds, and supplies a general and efficient strategy for construction of structurally complex and diverse aza-[n.2.1] skeletons. The [3+2]IMCC could be carried out under mild conditions and in gram scale. More importantly, 3-alkyl-substituted aziridines were also successful. The excellent structural diversity, the facile operation and the versatile post-modifications will support the applications of the [3+2]IMCC in natural products synthesis and drugs discovery.

Intramolecular Parallel [4+3] Cycloadditions of Cyclopropane 1,1-Diesters with [3]Dendralenes: Efficient Construction of [5.3.0]Decane and Corresponding Polycyclic Skeletons.

Aiming to develop efficient and general strategies for construction of complex and diverse polycyclic skeletons, we have successfully developed [4+3]IMPC (intramolecular parallel cycloaddition) of cyclopropane 1,1-diesters with [3]dendralenes. With a combination of the [4+3]IMPC and subsequent [4+n] cycloadditions, trans-[5.3.0]decane skeleton and its corresponding structurally complex and diverse polycyclic variants could be constructed efficiently. This novel [4+3] cycloaddition reaction mode of donor-acceptor cyclopropanes proceeds as a result of the ring-strain relief of a trans-[3.3.0]octane. We strongly believe that the developed methods will demonstrate potential applications in natural products synthesis and drug discovery.

TfOH-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1-diesters with nitriles.

A triflic acid-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1-diesters with nitriles was developed. This reaction was expeditious, and the scope of the substituents in both cyclopropanes and nitriles was broad. This supplies an efficient and practical method for the synthesis of 1-pyrrolines.

Aberrant Expression of SLC7A11 Impairs the Antimicrobial Activities of Macrophages in Staphylococcus Aureus Osteomyelitis in Mice.

Staphylococcus aureus (S. aureus) persistence in macrophages, potentially a reservoir for recurrence of chronic osteomyelitis, contributes to resistance and failure in treatment. As the mechanisms underlying survival of S. aureus in macrophages remain largely unknown, there has been no treatment approved. Here, in a mouse model of S. aureus osteomyelitis, we identified significantly up-regulated expression of SLC7A11 in both transcriptomes and translatomes of CD11b+F4/80+ macrophages, and validated a predominant distribution of SLC7A11 in F4/80+ cells around the S. aureus abscess. Importantly, pharmacological inhibition or genetic knockout of SLC7A11 promoted the bactericidal function of macrophages, reduced bacterial burden in the bone and improved bone structure in mice with S. aureus osteomyelitis. Mechanistically, aberrantly expressed SLC7A11 down-regulated the level of intracellular ROS and reduced lipid peroxidation, contributing to the impaired bactericidal function of macrophages. Interestingly, blocking SLC7A11 further activated expression of PD-L1 via the ROS-NF-κB axis, and a combination therapy of targeting both SLC7A11 and PD-L1 significantly enhanced the efficacy of clearing S. aureus in vitro and in vivo. Our findings suggest that targeting both SLC7A11 and PD-L1 is a promising therapeutic approach to reprogram the bactericidal function of macrophages and promote bacterial clearance in S. aureus osteomyelitis.

Cohort profile: the maternal-infant research on environmental chemicals research platform.

BACKGROUND: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health. METHODS: Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the study's Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies. RESULTS: Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada. CONCLUSIONS: The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals.

Analysis of heavy metals in the conversion of lake sediment and restaurant waste by black soldier fly (Hermetia illucens).

The risk posed by heavy metals makes it difficult to dispose of sediment contaminants from dredging lakes in China. Black soldier fly (Hermetia illucens) can convert organic waste, such as restaurant waste and lake sediment, to high-value-added protein feed and fertilizer. Experimental groups were formed in this study to explore the conversion of heavy metals present in the mixture of restaurant waste and lake sediment by black soldier fly larvae (BSFL). The results demonstrated that BSFL could survive in pure sediment with an 84.76% survival rate. Relative to the substrate, BSFL could accumulate 70-90% zinc (Zn), chromium (Cr), copper (Cu), and 20-40% cadmium (Cd) and lead (Pb). The experimental group 2:3, with 40% lake sediment and 60% restaurant waste, was the best group after conversion for 15 days, which showed a 95.24% survival rate of BFSL, 82.20 mg average weight of BFSL, 8.92 mm average length of BFSL, with varying content of heavy metals such as Cu (43.22 mg/kg), Zn (193.31 mg/kg), Cd (1.58 mg/kg), Cr (25.30 mg/kg) Cr, and Pb (38.59 mg/kg) in BSFL. Furthermore, the conversion residue conforms to the relevant standards of organic fertilizer in China and can be used as organic fertilizer. Overall, the present study shows that black soldier flies can improve the resource utilization of lake sediment, especially by reducing the effect of heavy metals.

Uranium uptake is mediated markedly by clathrin-mediated endocytosis and induce dose-dependent toxicity in HK-2 cells.

The objective of this study was to explore the endocytosis mechanisms of uranium uptake in HK-2 cells and its toxic effects. Our results demonstrated that uranium exposure impairs redox homeostasis and increases the permeability of the cell membrane and mitochondrial membrane, which may induce cell apoptosis by cytochrome-c leakage. Alkaline phosphatase activity increased after uranium exposure, which may be involved in the process of intracellular mineralisation of uranium, leading to severe cell necrosis. Furthermore, our findings demonstrated that the clathrin-mediated endocytosis process contributed substantially to uranium uptake in HK-2 cells and the total uranium uptake was highly correlated with cell viability, reaching a high correlation coefficient (r = -0.853) according to Pearson correlation analysis. In conclusion, the uptake of uranium into mammalian cells was mainly facilitated by the clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, cell apoptosis and necrosis.

Novel Nitrophenyl Substituted Anthranilic Diamide Derivatives: Design, Synthesis, Selectivity, and Antiresistance.

Diamide insecticides have gained popularity due to their high efficacy and low toxicity to nontarget organisms. However, diamide-associated resistance has emerged recently, causing a significant reduction in their potency, thereby hindering sustainable agricultural development. Here, we explored novel diamide insecticide analogs and, using a structure-based approach, rationally designed and synthesized 28 nitrophenyl substituted anthranilic diamides. Most of the compounds showed moderate to good activity against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compounds Ia and Im showed extraordinarily high activity and their mode of action was verified on isolated neurons. Additionally, Im exhibited over 10-fold greater potency than chlorantraniliprole in a HEK293 cell line stably expressing S. frugiperda ryanodine receptors (SfRyRs) containing the resistance mutations, G4891E and I4734M. The binding modes of Im in the SfRyRs were predicted using in silico molecular docking analysis. Our novel nitrophenyl substituted anthranilic diamide derivatives provide valuable insights for the design of insecticidal RyR-targeting compounds to effectively control both wild type and diamide insecticide-resistant lepidopteran pests.

Novel Sulfonylurea Derivatives as Potential Antimicrobial Agents: Chemical Synthesis, Biological Evaluation, and Computational Study.

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide health threat and has already tormented humanity during its long history, creating an urgent need for the development of new classes of antibacterial agents. In this study, twenty-one novel sulfonylurea derivatives containing phenyl-5-vinyl and pyrimidinyl-4-aryl moieties were designed and synthesized, among which, nine compounds exhibited inhibitory potencies against Gram-positive bacterial strains: MRSA (Chaoyang clinical isolates), S. aureus ATCC6538, vancomycin-resistant Enterococci-309 (VRE-309), and Bacillus subtilis ATCC 6633. Especially, 9i and 9q demonstrated inhibitory activities against the four bacterial strains with minimum inhibitory concentrations (MICs) of 0.78-1.56 µg/mL, and quite a few of other MRSA clinical strains with MICs of 0.78 µg/mL, superior to those of the positive controls vancomycin (MIC of 1 µg/mL) and methicillin (MIC of >200 µg/mL). This is the very first time that sulfonylurea derivatives have been identified as promising inhibitors against different MRSA clinical isolates. In addition, all the MIC values of the synthesized compounds against Candida albicans were greater than 100 µg/mL. Since the reported anti-Candida activities of sulfonylureas were due to acetohydroxyacid synthase (AHAS) inhibition, the molecular target against MRSA for the target sulfonylureas was thought to be a different mode of action. Density functional theory (DFT) calculations were finally performed to understand the structure-activity relationships, based on which, significant differences were observed between their HOMO maps for compounds with strong antibacterial activities and weak anti-MRSA effects. The present results hence provide valuable guidance for the discovery of novel agents to treat bacterial infections, especially against MRSA.

Challenges and trends in the determination of selected chemical contaminants and allergens in food.

This article covers challenges and trends in the determination of some major food chemical contaminants and allergens, which-among others-are being monitored by Health Canada's Food Directorate and for which background levels in food and human exposure are being analyzed and calculated. Eleven different contaminants/contaminant groups and allergens have been selected for detailed discussion in this paper. They occur in foods as a result of: use as a food additive or ingredient; processing-induced reactions; food packaging migration; deliberate adulteration; and/or presence as a chemical contaminant or natural toxin in the environment. Examples include acrylamide as a food-processing-induced contaminant, bisphenol A as a food packaging-derived chemical, melamine and related compounds as food adulterants and persistent organic pollutants, and perchlorate as an environmental contaminant. Ochratoxin A, fumonisins, and paralytic shellfish poisoning toxins are examples of naturally occurring toxins whereas sulfites, peanuts, and milk exemplify common allergenic food additives/ingredients. To deal with the increasing number of sample matrices and analytes of interest, two analytical approaches have become increasingly prevalent. The first has been the development of rapid screening methods for a variety of analytes based on immunochemical techniques, utilizing ELISA or surface plasmon resonance technology. The second is the development of highly sophisticated multi-analyte methods based on liquid chromatography coupled with multiple-stage mass spectrometry for identification and simultaneous quantification of a wide range of contaminants, often with much less requirement for tedious cleanup procedures. Whereas rapid screening methods enable testing of large numbers of samples, the multi analyte mass spectrometric methods enable full quantification with confirmation of the analytes of interest. Both approaches are useful when gathering surveillance data to determine occurrence and background levels of both recognized and newly identified contaminants in foods in order to estimate human daily intake for health risk assessment.