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.

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.

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.

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.

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.

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.

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.

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.

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.

Subdural anaplastic large-cell lymphoma presenting as a subacute epidural hematoma on imaging: A case report.

RATIONALE: Subdural anaplastic large-cell lymphoma (SALCL) is an extremely rare subtype of primary central nervous system (CNS) lymphoma. Here, we report a very rare subdural lymphoma case, which was misdiagnosed as a subacute epidural hematoma based on the radiological examination. PATIENT CONCERNS: We present the case of an 82-year-old patient who presented with a 2-day history of headache and consciousness disorder following head injury. Computed tomography of the head revealed a fusiform isodense/slightly dense shadow under the right temporoparietal occipital cranial plate, suggesting a subacute epidural hematoma. It was initially misdiagnosed as a right traumatic subacute epidural hematoma with hemiplegia of the left limb. According to the patient's condition, an emergency craniotomy was performed to remove the hematoma. However, it was found that the lesion was located under the dura mater and was yellowish-brown with yellowish-brown liquid inside. The appearance of the lesion looked like bean curd residue. Histopathological examination diagnosed ALCL. DIAGNOSIS: SALCL presenting as a subacute epidural hematoma on imaging. INTERVENTIONS: Operation. OUTCOMES: The patient died 1 month after being discharged automatically. CONCLUSIONS: This report shows a rare radiography presentation of SALCL. SALCL can mimic the appearance of an epidural hematoma and should be regarded as a differential diagnosis even in patients with a history of craniocerebral injury and the "typical" imaging appearance of an epidural hematoma. The report is hoped to provide a scientific reference for the clinical diagnosis of subdural lymphoma.

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.

Highly efficient construction of an oxa-[3.2.1]octane-embedded 5-7-6 tricyclic carbon skeleton and ring-opening of the bridged ring via C-O bond cleavage.

We report herein a highly efficient strategy for construction of a bridged oxa-[3.2.1]octane-embedded 5-7-6 tricyclic carbon skeleton through [3 + 2] IMCC (intramolecular [3 + 2] cross-cycloaddition), and the substituents and/or stereochemistries on C-4, C-6, C-7 and C-10 fully match those in the rhamnofolane, tigliane and daphnane diterpenoids. Furthermore, ring-opening of the bridged oxa-[3.2.1]octane via C-O bond cleavage was also successfully achieved.

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.

Studies toward the Total Syntheses of Calyciphylline D-Type Daphniphyllum Alkaloids.

An efficient construction of an aza-[5.7.6.5] tetracyclic core structure of calyciphylline D-type Daphniphyllum alkaloids has been achieved. The synthetic route features a diastereoselective cyclopropanation, efficient construction of the core bridged 8-aza-[3.2.1]octane skeleton through a [3 + 2] IMCC strategy, oxidative dearomatization of phenol, and gram-scale preparation in each step.

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.

A green route for pyrolysis poly-generation of typical high ash biomass, rice husk: Effects on simultaneous production of carbonic oxide-rich syngas, phenol-abundant bio-oil, high-adsorption porous carbon and amorphous silicon dioxide.

Rice husk is a widespread agriculture waste in rice-farming country. High silica content in rice husk prevent its efficient utilization. So in this work, concept of poly-generation was introduced to improve its utilization value. This study provided CO-rich syngas, phenol-abundant bio-oil, high-adsorption porous carbon and amorphous SiO2 as four end products for first time via combination of acid washing and activated carbon catalyst. Specifically, acid washing effectively decreasedsoluble ash, which altered pyrolysis paths, increased volatiles release and reduced impurities in bio-char. After catalytic pyrolysis, phenol content of 65.56% and CO of 56.09 vol% were detected in bio-oil and syngas from AWRH. For solid products, acid washing benefited both bio-char and silica. A low-cost porous carbon with developed pores and rich surface functional groups was prepared for water absorption. And high purity amorphous SiO2 was recycled from alkali etching solution. Finally, a green process with no waste emission was proposed.

Perchlorate in human milk samples from the maternal-infant research on environmental chemicals study (MIREC).

Perchlorate is a low molecular weight highly soluble anion. It occurs naturally in the environment, primarily near potash deposits and in arid regions. The determination of perchlorate in human milk is of interest in vulnerable populations such as infants and pregnant women. In this study, a sensitive and selective isotope dilution ion chromatography/tandem mass spectrometry (ID IC-MS/MS) method was developed and validated for the determination of perchlorate in human milk samples collected from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. The limit of detection (LOD) was 0.27 µg·kg-1 for human milk. A total of 439 human milk samples were analysed with measurable levels of perchlorate in most of the milk samples, and the mean value was 7.62 ± 32.7 µg·kg-1. This project provided important information related to perchlorate levels in human milk collected across Canada and the extent to which pregnant women and their infants may be exposed to perchlorate. A dietary exposure assessment was also conducted in infants based on the measured values in human milk. The mean perchlorate probable daily intakes (PDIs) for infants consuming human milk were 0.31 ± 0.07 µg/kg bw/day for infants under 1 year and 0.17 ± 0.10 µg/kg bw/day for infants between 1 and 3 years old. None of the estimates exceeded the FAO/WHO provisional maximum tolerable daily intake (PMTDI) of 10 µg/kg bw/day.

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.