Spleen tyrosine kinase inhibitor R406 has both antiviral and anti-inflammatory effects on severe influenza A infection.

Death due to severe influenza is usually a fatal complication of a dysregulated immune response more than the acute virulence of an infectious agent. Although spleen tyrosine kinase (SYK) as a critical immune signaling molecule and therapeutic target plays roles in airway inflammation and acute lung injury, the role of SYK in influenza virus infection is not clear. Here, we investigated the antiviral and anti-inflammatory effects of SYK inhibitor R406 on influenza infection through a coculture model of human alveolar epithelial (A549) and macrophage (THP-1) cell lines and mouse model. The results showed that R406 treatment increased the viability of A549 and decreased the pathogenicity and mortality of lethal influenza virus in mice with influenza A infection, decreased levels of intracellular signaling molecules under the condition of inflammation during influenza virus infection. Combination therapy with oseltamivir further ameliorated histopathological damage in the lungs of mice and further delayed the initial time to death compared with R406 treatment alone. This study demonstrated that phosphorylation of SYK is involved in the pathogenesis of influenza, and R406 has antiviral and anti-inflammatory effects on the treatment of the disease, which may be realized through multiple pathways, including the already reported SYK/STAT/IFNs-mediated antiviral pathway, as well as TNF-α/SYK- and SYK/Akt-based immunomodulation pathway.

Enhanced Photocatalytic Activity of Hyper-Cross-Linked Polymers Toward Amines Oxidation Coupled with H2 O2 Generation through Extending Monomer's Conjugation Degree.

Visible-light-driven amines oxidation coupled with hydrogen peroxide (H2 O2 ) generation is a promising way to convert solar energy to chemical energy. Herein, a series of hyper-cross-linked polymers (HCPs) photocatalysts with different arenes monomers, including benzene (BE), diphenyl (DP), p-terphenyl (TP), or p-quaterphenyl (QP), were synthesized by simple Friedel-Crafts alkylation reaction. Owing to the maximum monomer's conjunction degree and excellent oxygen (O2 ) adsorption capacity, QP-HCPs exhibited highest photocatalytic activity for benzylamine oxidation coupled with H2 O2 generation under the irradiation of 455 nm Blue LED lamp. More than 99 % of benzylamine could be converted to N-benzylidenebenzylamine within 60 min. In addition, nearly stoichiometric H2 O2 was synchronously obtained with a high production rate of 9.3 mmol gcat -1 h-1 . Our work not only demonstrated that the photocatalytic activity of HCPs photocatalysts significantly depends on monomer's conjunction degree, but also provided a new strategy for converting solar energy to chemical energy.

Free Radical Promoted Trifluoromethylthiolation of Alkynes to Access SCF3-Containing Dibenzazepines or Dioxodibenzothiazepines.

Persulfate-promoted radical cascade trifluoromethylthiolation of aryl acetylenes with AgSCF3 provides a simple reaction system for the synthesis of SCF3-substituted dibenzazepines or dioxodibenzothiazepines with good Z/E selectivity. The single-crystal X-ray diffraction data confirms the structures of the final products. A series of scaled-up experiments, further transformations, and radical inhibition experiments were operated in the reaction system.

Catalytic Synthesis of Formamides by Integrating CO2 Capture and Morpholine Formylation on Supported Iridium Catalyst.

Herein we report an efficient and recyclable catalytic system for tandem CO2 capture and N-formylation to value-added chemicals. CO2 is apt to be captured by morpholine solution, while a highly efficient heterogeneous catalyst, isolated iridium atoms supported over nanadiamond/graphene, is discovered to be highly reactive for the formylation of morpholine, leading to the formation of N-formylmorpholine with excellent productivity (with a turnover number of 5 120 000 in a single batch reaction) and selectivity (>99 %). In addition, the CO2 captured by morpholine under atmospheric conditions can be converted to N-formylmorpholine with decent conversion (51 %), which realizes the integration of CO2 capture and conversion to value-added chemicals.

Rapid enhancement of chemical weathering recorded by extremely light seawater lithium isotopes at the Permian-Triassic boundary.

Lithium (Li) isotope analyses of sedimentary rocks from the Meishan section in South China reveal extremely light seawater Li isotopic signatures at the Permian-Triassic boundary (PTB), which coincide with the most severe mass extinction in the history of animal life. Using a dynamic seawater lithium box model, we show that the light seawater Li isotopic signatures can be best explained by a significant influx of riverine [Li] with light δ7Li to the ocean realm. The seawater Li isotope excursion started ≥300 Ky before and persisted up to the main extinction event, which is consistent with the eruption time of the Siberian Traps. The eruption of the Siberian Traps exposed an enormous amount of fresh basalt and triggered CO2 release, rapid global warming, and acid rains, which in turn led to a rapid enhancement of continental weathering. The enhanced continental weathering delivered excessive nutrients to the oceans that could lead to marine eutrophication, anoxia, acidification, and ecological perturbation, ultimately resulting in the end-Permian mass extinction.

A Comparative Study on the Clinical Features of Coronavirus 2019 (COVID-19) Pneumonia With Other Pneumonias.

BACKGROUND: A novel coronavirus (COVID-19) has raised world concern since it emerged in Wuhan, China in December 2019. The infection may result in severe pneumonia with clusters of illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen COVID-19 and 15 other patients with pneumonia (non-COVID-19) in areas outside of Hubei were involved in this study. Both COVID-19 and non-COVID-19 patients were confirmed to be infected using throat swabs and/or sputa with/without COVID-2019 by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the differences between COVID-19 and non-COVID-19. RESULTS: All patients had a history of exposure to confirmed cases of COVID-19 or travel to Hubei before illness. The median (IQR) duration was 8 (6-11) and 5 (4-11) days from exposure to onset in COVID-19 and non-COVID-19 cases, respectively. The clinical symptoms were similar between COVID-19 and non-COVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) COVID-19 but 4 (26.67%) non-COVID-19 patients had bilateral involvement while 17 COVID-19 patients (89.47%) but 1 non-COVID-19 patient (6.67%) had multiple mottling and ground-glass opacity on chest CT images. Compared with non-COVID-19, COVID-19 presents remarkably more abnormal laboratory tests, including AST, ALT, γ-GT, LDH, and α-HBDH. CONCLUSIONS: The COVID-19 infection has onsets similar to other pneumonias. CT scan may be a reliable test for screening COVID-19 cases. Liver function damage is more frequent in COVID-19 than non-COVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of COVID-19.

Correlates of HIV-infection among men who have sex with men: results from a community-based, cross-sectional study in Tianjin, China.

China has 747,000 confirmed HIV/AIDS cases and sexual transmission between men who have sex with men (MSM) is the most prevalent mode of transmission. Our study aims to (a) examine HIV prevalence and behavioral risk factors for HIV infection among 1900 MSM recruited from a community-based organization in Tianjin, China, and (b) describe HIV treatment outcomes for those diagnosed with HIV. We used multivariable logistic regression to identify which socio-demographics and behaviors were associated with HIV infection. The overall HIV prevalence was 3.95%. Key behavioral risk factors included: receptive sex role, older age at first sex with man, condomless anal sex, and having used 2+ drugs. Of those living with HIV, 83% were successfully enrolled in antiretroviral therapy and those enrolled were all virally suppressed after one year. These findings highlight key behavioral risk factors for HIV infection in Tianjin, China and can inform interventions to preventing further HIV transmission.

Epidemiology of human infections with avian influenza A(H7N9) virus in China.

BACKGROUND: The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. METHODS: Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. RESULTS: Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus. CONCLUSIONS: Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

Graphene Oxide Catalyzed C-H Bond Activation: The Importance of Oxygen Functional Groups for Biaryl Construction.

A heterogeneous, inexpensive, and environmentally friendly graphene oxide catalytic system for the C-H bond arylation of benzene enables the formation of biaryl compounds in the presence of aryl iodides. The oxygen functional groups in these graphene oxide sheets and the addition of KOtBu are essential for the observed catalytic activity. Reactions with various model compounds and DFT calculations confirmed that these negatively charged oxygen atoms promote the overall transformation by stabilizing and activating K(+) ions, which in turns facilitates the activation of the C-I bond. However, the graphene π system also greatly facilitates the overall reaction as the aromatic coupling partners are easily adsorbed.

Escherichia coli Free Radical-Based Killing Mechanism Driven by a Unique Combination of Iron Restriction and Certain Antibiotics.

UNLABELLED: Bacterial resistance to antibiotics is precipitating a medical crisis, and new antibacterial strategies are being sought. Hypothesizing that a growth-restricting strategy could be used to enhance the efficacy of antibiotics, we determined the effect of FDA-approved iron chelators and various antibiotic combinations on invasive and multidrug-resistant extraintestinal pathogenic Escherichia coli (ExPEC), the Gram-negative bacterium most frequently isolated from the bloodstreams of hospitalized patients. We report that certain antibiotics used at sublethal concentrations display enhanced growth inhibition and/or killing when combined with the iron chelator deferiprone (DFP). Inductively coupled plasma optical emission spectrometry reveals abnormally high levels of cell-associated iron under these conditions, a response that correlates with an iron starvation response and supraphysiologic levels of reactive oxygen species (ROS). The high ROS level is reversed upon the addition of antioxidants, which restores bacterial growth, suggesting that the cells are inhibited or killed by excessive free radicals. A model is proposed in which peptidoglycan-targeting antibiotics facilitate the entry of lethal levels of iron-complexed DFP into the bacterial cytoplasm, a process that drives the generation of ROS. This new finding suggests that, in addition to restriction of access to iron as a general growth-restricting strategy, targeting of cellular pathways or networks that selectively disrupt normal iron homeostasis can have potent bactericidal outcomes. IMPORTANCE: The prospect that common bacteria will become resistant to all antibiotics is challenging the medical community. In addition to the development of next-generation antibiotics, new bacterial targets that display cytotoxic properties when altered need to be identified. Data presented here demonstrate that combining subinhibitory levels of both iron chelators and certain antibiotics kills pathogenic Escherichia coli. The mechanism of this effect is the production of supraphysiologic levels of reactive oxygen species, likely powered by the excessive import of iron. These findings were consistent for both clinically relevant and no longer clinically used antibiotics and may extend to Staphylococcus aureus as well.

Microwave-assisted radiosynthesis of [(18) F]ASEM, a radiolabeled α7-nicotinic acetylcholine receptor antagonist.

An improvement of the original radiochemical synthesis of [(18) F]ASEM, an α7-nicotinic acetylcholinergic receptor radioligand, is reported. The new procedure utilizes microwave-assisted radiofluorination. In addition, a new preparative HPLC method was developed to eliminate a chemical impurity in the final product. Quality control procedures were also enhanced to improve detection of product with enhanced resolution of potential impurities. [(18) F]ASEM was produced in 20.1 ± 8.9% non-decay corrected (NDC) yield with an average synthesis time of 57 min and an average specific radioactivity of 856 ± 332 GBq/µmol (23 ± 9 Ci/µmol).

Pd-Pb Alloy Nanocrystals with Tailored Composition for Semihydrogenation: Taking Advantage of Catalyst Poisoning.

Metallic nanocrystals (NCs) with well-defined sizes and shapes represent a new family of model systems for establishing structure-function relationships in heterogeneous catalysis. Here in this study, we show that catalyst poisoning can be utilized as an efficient strategy for nanocrystals shape and composition control, as well as a way to tune the catalytic activity of catalysts. Lead species, a well-known poison for noble-metal catalysts, was investigated in the growth of Pd NCs. We discovered that Pb atoms can be incorporated into the lattice of Pd NCs and form Pd-Pb alloy NCs with tunable composition and crystal facets. As model catalysts, the alloy NCs with different compositions showed different selectivity in the semihydrogenation of phenylacetylene. Pd-Pb alloy NCs with better selectivity than that of the commercial Lindlar catalyst were discovered. This study exemplified that the poisoning effect in catalysis can be explored as efficient shape-directing reagents in NC growth, and more importantly, as a strategy to tailor the performance of catalysts with high selectivity.

Wet and dry atmospheric depositions of inorganic nitrogen during plant growing season in the coastal zone of Yellow River Delta.

The ecological problems caused by dry and wet deposition of atmospheric nitrogen have been widespread concern in the world. In this study, wet and dry atmospheric depositions were monitored in plant growing season in the coastal zone of the Yellow River Delta (YRD) using automatic sampling equipment. The results showed that SO4 (2-) and Na(+) were the predominant anion and cation, respectively, in both wet and dry atmospheric depositions. The total atmospheric nitrogen deposition was ~2264.24 mg m(-2), in which dry atmospheric nitrogen deposition was about 32.02%. The highest values of dry and wet atmospheric nitrogen deposition appeared in May and August, respectively. In the studied area, NO3 (-)-N was the main nitrogen form in dry deposition, while the predominant nitrogen in wet atmospheric deposition was NH4 (+)-N with ~56.51% of total wet atmospheric nitrogen deposition. The average monthly attribution rate of atmospheric deposition of NO3 (-)-N and NH4 (+)-N was ~31.38% and ~20.50% for the contents of NO3 (-)-N and NH4 (+)-N in 0-10 cm soil layer, respectively, suggested that the atmospheric nitrogen was one of main sources for soil nitrogen in coastal zone of the YRD.

Facile synthesis of FeNi alloy-supported N-doped Mo2C hollow nanospheres for the oxygen evolution reaction.

The rapid depletion of fossil fuels results in significant environmental pollution. Consequently, researching environmentally friendly and cost-effective electrocatalysts with exceptional oxygen evolution reaction (OER) capabilities holds immense importance in enhancing the efficient utilization of resources. In this paper, a straightforward and cost-effective method was employed to produce Fe-Ni alloy-supported N-doped carbon hollow nanospheres (FeNi/Mo2C/NC) using self-assembled molybdenum dopamine spheres (Mo-PDA-HS) as a substrate. The inclusion of iron and nickel addressed the issue of aggregation and collapse in Mo-PDA-HS nanostructures at high temperatures, while adjusting the electronic structure of the composites to achieve efficient OER activity. The composite displayed a low overpotential (η10 mA = 304 mV) and a minimal Tafel slope (41.8 mV/dec-1). This study introduces a simple strategy for constructing structurally robust and non-aggregating Mo2C nanostructures, along with a direct method for designing cost-effective and high-performance catalysts for OER.

Metal-free radical bicyclization/chloroalkylarylation of 1,6-enynes with chloroalkanes.

Free radical initiated bicyclization of 1,6-enynes with chloralkanes, is achieved via selective activation of the C(sp3)-H bond of the chloralkane, resulting in diverse polychlorinated/chlorinated polyheterocycles. Two kinds of transformations and a scaled-up experiment were performed to test the synthetic importance of the organic chlorides. Finally, a range of radical inhibition operations and radical clock tests were explored to support the reaction process.

Design of iron oxyhydroxide nanosheets coated on Co species embedded in nanoporous carbon for oxygen evolution reaction.

There is still a tremendous challenge in designing environmentally friendly oxygen evolution reaction (OER) catalysts that are inexpensive and high-performing for practical applications. Herein, the self-sacrificing template zeolitic imidazolate framework-67 (ZIF-67) was pyrolyzed under N2 atmosphere to generate Co species embedded in nanoporous carbon (Co-NC). Then, iron oxyhydroxide (FeOOH) was wrapped onto the Co-NC surface via electrodeposition to shape the Co-NC@FeOOH composites. Benefiting from the core-shell structure, high conductivity, and distributed active sites, Co-NC@FeOOH presents distinguished OER performance with a low overpotential (336 mV) at 10 mA cm-2 and small Tafel slope (49.46 mV dec-1). This work furnishes a rosy passage for receiving cost-effective electrocatalysts with high efficiency for OER.

Facile synthesis of Co-Fe layered double hydroxide nanosheets wrapped on Ni-doped nanoporous carbon nanorods for oxygen evolution reaction.

Owing to the high demand for clean and renewable energy technologies, several studies have focused on developing economically feasible, highly effective, and stable non-precious electrocatalysts for promoting the oxygen evolution reaction (OER). This development has stimulated an expansion of investigative quests and indicated the importance of advancing electrocatalytic research in this field. Through a facile and efficient method, Ni nanoparticles were uniformly embedded into nanoporous carbon nanorods (Ni-NCN), which are subsequently electrodeposited on CoFe-layered double hydroxide (LDH) nanosheets to produce highly efficient Ni-NCN/CoFe-LDH composites used for OER. The composite exhibited excellent catalytic activity toward OER owing to its low overpotential (ƞ10 mA = 280 mV), small Tafel slope (42 mV dec-1), and excellent durability. The Ni-NCN/CoFe-LDH catalyst exhibited higher OER activity owing to its uniformly dispersed Ni nanoparticles, large specific surface area, enhanced electron transport, and synergistic effect of multiple composites. Additionally, the enhanced synergistic effect of Ni-NCN promoted higher OER performance compared with Ni-undoped carbon nanorod/LDH, indicating that the Ni dopant and LDH significantly contributed to the overall OER performance. The synergistic effect of multiple composites significantly contributed to the excellent OER performance, indicating their potential as OER catalyst.

Facile synthesis of Co-Ni layered double hydroxides nanosheets wrapped on a prism-like metal-organic framework for efficient oxygen evolution reaction.

The construction of low-cost oxygen evolution reaction (OER) electrocatalysts with high activity and good durability is a considerable challenge for facilitating the efficient utilization of green energy. Herein, the prism-like materials of institute lavoisier frameworks-88 (MIL-88) was first synthesized by a hydrothermal method. Then, Co-Ni layered double hydroxides (CoNi-LDHs) nanosheets were directly wrapped on the MIL-88 surface by electrodeposition to form core-shell MIL-88@CoNi-LDHs composites. Due to the distinct structure and synergistic effect between the MIL-88 core and CoNi-LDHs shell, it was found that MIL-88@CoNi-LDHs had outstanding OER activity with a small Tafel slope (45.55 mV dec-1), low overpotential (314 mV) at 10 mA cm-2, and superior durability. This study provides a prospective pathway to exploit highly efficient low-cost electrocatalysts for OER.

Highly dispersed Co anchored on Ce-doped hydroxyapatite as a dual-functional catalyst for selective hydrogenolysis of 5-hydroxymethylfurfural.

Hydrodeoxygenation (HDO) is an indispensable approach to produce renewable biofuels and value-added chemicals using natural biomass and its derivatives. 2,5-Dimethylfuran (DMF) is considered to be a very promising liquid biofuel, and it can be fabricated by HDO of the biomass derivative 5-hydroxymethylfurfural (HMF). Herein, a highly efficient bifunctional catalyst, Co/HAP(Ce), was fabricated by anchoring highly dispersed Co on Ce-doped hydroxyapatite (HAP(Ce)). Co/HAP(Ce) displayed excellent HDO catalytic activity to convert HMF to DMF, and 99% HMF conversion and 96% DMF selectivity can be obtained under 150 °C, 2 MPa H2 conditions for 5 h. Density functional theory calculations revealed that H2 can be more easily activated by Co/HAP(Ce). Systematic studies confirmed that the high activity of Co/HAP(Ce) can be ascribed to the desired acid-alkali properties, highly dispersed cobalt species and strong metal-support interactions. This research provides a cost effective approach for designing efficient catalysts for HDO of biomass and its derivatives.

Immunogenicity and safety of a live attenuated varicella vaccine co-administered with inactive hepatitis A vaccine: A phase 4, single-center, randomized, controlled trial.

Co-administration of vaccines can facilitate the introduction of new vaccines in immunization schedules. This study aimed to evaluate the immunogenicity and safety of co-administration with live attenuated varicella vaccine (VarV) and inactivated hepatitis A vaccine (HepA) among children aged 12 ~ 15 months. In this phase 4 clinical trial, 450 children were randomized with a ratio of 1:1 to receive VarV and Hep A simultaneously (Group A) or separately (Group B). The primary endpoints were the seroconversion rate of anti-varicella-zoster virus (VZV) antibodies 42 days after vaccination of VarV and the seroconversion rate of anti-Hepatitis A virus (HAV) antibodies 30 days after two-dose vaccination of HepA. After full immunization, the seroconversion rates of anti-VZV antibodies were 91.79% in Group A and 92.15% in Group B; the geometric mean titers (GMTs) were 11.80 and 12.19, respectively. The seroconversion rates of anti-HAV antibodies were 99.48% in Group A and 100.0% in Group B; the geometric mean concentrations (GMCs) reached 9499.11 and 9528.36 mIU/ml, respectively. The lower limits of the 95% CI for the seroconversion difference of anti-VZV antibodies and anti-HAV antibodies were -5.86% and -2.90%, which greater than the predefined non-inferiority margin (-10%). The incidence rate of adverse reactions in Group A was lower than Group B (9.33% vs 16.22%), and only one serious adverse event was reported in Group B, which was unrelated to the study vaccine. In conclusion, the co-administration of VarV with HepA has non-inferior immunogenicity and safety profiles were quite comparable with the separate administration of both vaccines.Trial registration number: NCT05526820 (ClinicalTrials.gov).