Influenza D virus infection in China, 2022-2023.

Influenza D virus (IDV) plays an important role in the bovine respiratory disease (BRD) complex. Its potential for the zoonotic transmission is of particular concern. In China, IDV has previously been identified in agricultural animals by molecular surveys with no live virus isolates reported. In this study, live IDVs were successfully isolated from cattle in China, which prompted us to further investigate the national prevalence, antigenic property, and infection biology of the virus. IDV RNA was detected in 11.1% (51/460) of cattle throughout the country in 2022-2023. Moreover, we conducted the first IDV serosurveillance in China, revealing a high seroprevalence (91.4%, 393/430) of IDV in cattle during the 2022-2023 winter season. Notably, all the 16 provinces from which cattle originated possessed seropositive animals, and 3 of them displayed the 100% IDV-seropositivity rate. In contrast, a very low seroprevalence of IDV was observed in pigs (3%, 3/100) and goats (1%, 1/100) during the same period of investigation. Furthermore, besides D/Yama2019 lineage-like IDVs, we discovered the D/660 lineage-like IDV in Chinese cattle, which has not been detected to date in Asia. Finally, the Chinese IDVs replicated robustly in diverse cell lines but less efficiently in the swine cell line. Considering the nationwide distribution, high seroprevalence, and appreciably genetic diversity, further studies are required to fully evaluate the risk of Chinese IDVs for both animal and human health in China, which can be evidently facilitated by IDV isolates reported in this study.

SFTSV nucleoprotein mediates DNA sensor cGAS degradation to suppress cGAS-dependent antiviral responses.

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

Three-Component Assembly of Dihydropyrrolo[3,4-e][1,3]thiazines from Elemental Sulfur, Maleimides, and 1,3,5-Triazinanes.

A three-component reaction for the synthesis of dihydropyrrolo[3,4-e][1,3]thiazines has been developed. Elemental sulfur, maleimides, and 1,3,5-triazinanes are assembled together through sulfuration/nucleophilic attack in N-methylpyrrolidin-2-one (NMP) under mild conditions. A small amount of NaHCO3 is important for the activation of the reaction. In this method, sulfur plays a dual role in thiazine ring formation, while triazinanes are utilized as three-atom synthons in the annulation reaction.

Numerical Investigation on the Structural Behavior of a Short-Span Cable-Stayed Bridge with Steel and CFRP Hybrid Cables.

In this paper, a thorough investigation is presented on the static and dynamic behaviors of a short-span cable-stayed bridge (CSB) incorporating steel and carbon fiber reinforced polymer (CFRP) hybrid cables. The study focuses on the world's largest span and China's first highway, CFRP CSB. The performance of the CSB was compared using numerical simulations under four different cable patterns: steel cables, CFRP cables, and steel, and two types of hybrid cables with different structural arrangements. The results indicate that the use of the use of CFRP cables in the long cable region in the short-span CSB project investigated in this study offers improved performance in terms of stability, seismic response, and reduced displacements. In comparison to CFRP cables, hybrid cables have demonstrated a reduction of 12% in the maximum vertical displacement of the main girder. On the other hand, the hybrid cables result in reduced maximum internal forces and longitudinal and lateral displacements of the main girders and towers compared to steel cables. The difference in the arrangement of CFRP cables in the long cable region or short cable region is not obvious under dead loads, but significant differences still exist between the CFRP cable bridges in the short cable region and the long cable region in terms of live load effects, temperature effects, and dynamic characteristics.

Incidence and characteristic of deep venous thrombosis in hospitalized chronic heart failure patients.

BACKGROUND: This study was conducted to investigate the incidence of deep venous thrombosis (DVT), outcomes and its characteristics in patients with chronic heart failure (CHF) in a retrospective setting. OUTCOMES: Patients died of cardiac shock or acute exacerbation of heart failure (HF), admitted to intensive care unit (ICU) due to acute exacerbation of HF, patients decided to withdraw treatment and return home due to acute exacerbation of HF. METHODS: From January 2015 to June 2022, we admitted 359 patients diagnosed with CHF, and lower limb ultrasonography was performed for the examination of DVT after admission. The incidence of DVT was recorded and patients with known risk factors of VTE were identified and excluded after incidence of DVT was calculated. Patients' clinical data were then collected. RESULTS: The occurrence of DVT was 10.0% (36/359), as calf intramuscular vein thrombosis was the main constitution (n = 28, 75%). DVT patients with other factors (carcinoma, surgery, stroke, previous history of DVT) constituted a considerable part (33.3%, 12/36). Age, history of Diabetes Mellitus (DM), levels of DDi (D-Dimer), levels of alanine transferase (ALT) and left ventricular end-diastolic diameter (LVEDd) were independent predictors or risk factors of DVT in CHF patients, while chronic kidney disease (CKD) stage 1-4, white blood cell (WBC) and direct oral anticoagulant (DOAC) were protective factors. Incidence of DVT was correlated with a poor outcome of CHF patients (Pearson Chi-Square test, Value 19.612, P < 0.001). CONCLUSIONS: In this retrospective study, incidence of DVT was found to be relatively high among hospitalized CHF patients, while patients with DVT was associated with a poor prognosis.

Tanshinone IIA induces ER stress and JNK activation to inhibit tumor growth and enhance anti-PD-1 immunotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.

Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia.

Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.

Highly Optically Selective and Thermally Insulating Porous Calcium Silicate Composite SiO2 Aerogel Coating for Daytime Radiative Cooling.

Daytime radiative cooling technology offers a low-carbon, environmentally friendly, and nonpower-consuming approach to realize building energy conservation. It is important to design materials with high solar reflectivity and high infrared emissivity in atmospheric windows. Herein, a porous calcium silicate composite SiO2 aerogel water-borne coating with strong passive radiative cooling and high thermal insulation properties is proposed, which shows an exceptional solar reflectance of 94%, high sky window emissivity of 96%, and 0.0854 W/m·K thermal conductivity. On the SiO2/CaSiO3 radiative cooling coating (SiO2-CS-coating), a strategy is proposed to enhance the atmospheric window emissivity by lattice resonance, which is attributed to the eight-membered ring structure of porous calcium silicate, thereby increasing the atmospheric window emissivity. In the daytime test (solar irradiance 900W/m2, ambient temperature 43 °C, wind speed 0.53 m/s, humidity 25%), the temperature inside the box can achieve a cooling temperature of 13 °C lower than that of the environment, which is 30 °C, and the theoretical cooling power is 96 W/m2. Compared with the commercial white coating, SiO2-CS-coating can save 70 kW·h of electric energy in 1 month, and the energy consumption is reduced by 36%. The work provides a scalable, widely applicable radiative-cooling coating for building comfort, which can greatly reduce indoor temperatures and is suitable for building surfaces.

High Stretch Modulates cAMP/ATP Level in Association with Purine Metabolism via miRNA-mRNA Interactions in Cultured Human Airway Smooth Muscle Cells.

High stretch (>10% strain) of airway smooth muscle cells (ASMCs) due to mechanical ventilation (MV) is postulated to contribute to ventilator-induced lung injury (VILI), but the underlying mechanisms remain largely unknown. We hypothesized that ASMCs may respond to high stretch via regulatory miRNA-mRNA interactions, and thus we aimed to identify high stretch-responsive cellular events and related regulating miRNA-mRNA interactions in cultured human ASMCs with/without high stretch. RNA-Seq analysis of whole genome-wide miRNAs revealed 12 miRNAs differentially expressed (DE) in response to high stretch (7 up and 5 down, fold change >2), which target 283 DE-mRNAs as identified by a parallel mRNA sequencing and bioinformatics analysis. The KEGG and GO analysis further indicated that purine metabolism was the first enriched event in the cells during high stretch, which was linked to miR-370-5p-PDE4D/AK7. Since PDE4D/AK7 have been previously linked to cAMP/ATP metabolism in lung diseases and now to miR-370-5p in ASMCs, we thus evaluated the effect of high stretch on the cAMP/ATP level inside ASMCs. The results demonstrated that high stretch modulated the cAMP/ATP levels inside ASMCs, which could be largely abolished by miR-370-5p mimics. Together, these findings indicate that miR-370-5p-PDE4D/AK7 mediated high stretch-induced modulation of cAMP and ATP synthesis inside ASMCs. Furthermore, such interactive miRNA-mRNA pairs may provide new insights for the discovery of effective biomarkers/therapeutic targets for the diagnosis and treatment of VILI and other MV-associated respiratory diseases.

COL3A1 is a potential diagnostic biomarker for synovial chondromatosis and affects the cell cycle and migration of chondrocytes.

BACKGROUND: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC. METHODS: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene. RESULTS: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (COL3A1) and HSPA8, were notably expressed in SC tissues, with COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore, COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio. CONCLUSIONS: These results suggest that SC tissues contained the abundant GAG and collagen. COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC.

First report on establishment and characterization of the extrahepatic cholangiocarcinoma sarcoma cell line CBC2T-2.

BACKGROUND: Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice. These cells consist of both epithelial and mesenchymal cells. Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma. However, cholangiocarcinoma sarcoma cell lines are not available in cell banks. AIM: To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line, namely CBC2T-2. METHODS: We conducted a short tandem repeat (STR) test to confirm the identity of the CBC2T-2 cell line. Furthermore, we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies. The tumorigenic potential of CBC2T-2 cells was tested in vivo using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The cells were injected subcutaneously and tumor formation was observed. In addition, immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts. The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma. Lastly, whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line. RESULTS: The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue. The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology. The cells exhibited a high proliferation ratio with a doubling time of 47.11 h. This cell line has migratory, invasive, and clonogenic abilities. The chromosomes in the CBC2T-2 cells were polyploidy, with numbers ranging from 69 to 79. The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice. CBC2T-2 cells and xenografts were positive for both the epithelial marker, CK19, and the mesenchymal marker, vimentin. These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics. The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma, and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option. CONCLUSION: We established the first human cholangiocarcinoma sarcoma cell line, CBC2T-2, with stable biogenetic traits. This cell line, as a research model, has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.

Characterization of circRNAs in established osimertinib­resistant non­small cell lung cancer cell lines.

Drug resistance is an urgent problem to be solved in the treatment of non­small­cell lung cancer (NSCLC). Osimertinib is a third­generation EGFR­tyrosine kinase inhibitor, which can improve the efficacy and quality of life of patients; however, the inevitable resistance after long­term use of osimertinib often leads to treatment failure. Cell lines are key tools for basic and preclinical studies. At present, few osimertinib­resistant cell lines (HCC827­OR and H1975­OR) have been established. In the present study, osimertinib­resistant cell lines were established by gradually increasing the drug concentration. Half­maximal inhibitory concentration (IC50), cell morphology, whole exon sequencing, Cell Counting Kit­8 assay, EdU staining and flow cytometry were used to evaluate the osimertinib­resistant cell lines. Western blot analysis was used to detect the expression levels of key proteins involved in osimertinib resistance. The circular RNA (circRNA) expression profile was identified by RNA sequencing (RNA­seq) analysis of HCC827, HCC827­OR, H1975 and H1975­OR cells. Subsequently, the biological roles of differentially expressed circRNAs were explored in in vitro studies. Osimertinib­resistant cell lines were successfully established via treatment with an increasing concentration of osimertinib. Osimertinib IC50 and proliferation of resistant cells were much higher than those of sensitive cells. Notably, phosphorylated (p)­AKT and p­ERK were markedly activated in resistant cells, and the inhibitory effect of osimertinib on p­AKT and p­ERK was weaker in resistant cells than that in parental cells. RNA­seq analysis identified differentially expressed circRNAs in HCC827, HCC827­OR, H1975 and H1975­OR cells. The most dysregulated circRNAs (circPDLIM5 and circPPP4R1) were selected for further functional study. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the host genes of differentially expressed circRNAs were associated with 'endocytosis' and 'regulation of autophagy'. In conclusion, the present study established osimertinib­resistant cell lines and revealed that circRNAs may serve as a promising biomarker in NSCLC osimertinib resistance.

Lanatoside C decelerates proliferation and induces apoptosis through inhibition of STAT3 and ROS-mediated mitochondrial membrane potential transformation in cholangiocarcinoma.

Introduction: The incidence of cholangiocarcinoma (CCA) has increased worldwide in recent years. Given the poor prognosis associated with the current management approach of CCA, new therapeutic agents are warranted to improve the prognosis of this patient population. Methods: In this study, we extracted five cardiac glycosides (CGs) from natural plants: digoxin, lanatoside A, lanatoside C, lanatoside B, and gitoxin. Follow-up experiments were performed to assess the effect of these five extracts on cholangiocarcinoma cells and compounds with the best efficacy were selected. Lanatoside C (Lan C) was selected as the most potent natural extract for subsequent experiments. We explored the potential mechanism underlying the anticancer activity of Lan C on cholangiocarcinoma cells by flow cytometry, western blot, immunofluorescence, transcriptomics sequencing, network pharmacology and in vivo experiments. Results: We found that Lan C time-dependently inhibited the growth and induced apoptosis of HuCCT-1 and TFK-1 cholangiocarcinoma cells. Besides Lan C increased the reactive oxygen species (ROS) content in cholangiocarcinoma cells, decreased the mitochondrial membrane potential (MMP) and resulted in apoptosis. Besides, Lan C downregulated the protein expression of STAT3, leading to decreased expression of Bcl-2 and Bcl-xl, increased expression of Bax, activation of caspase-3, and initiation of apoptosis. N-acetyl-L-cysteine (NAC) pretreatment reversed the effect of Lan C. In vivo, we found that Lan C inhibited the growth of cholangiocarcinoma xenografts without toxic effects on normal cells. Tumor immunohistochemistry showed that nude mice transplanted with human cholangiocarcinoma cells treated with Lan C exhibited decreased STAT3 expression and increased caspase-9 and caspase-3 expression in tumors, consistent with the in vitro results. Conclusion: In summary, our results substantiates that cardiac glycosides have strong anti-CCA effects. Interestingly the biological activity of Lan C provides a new anticancer candidate for the treatment of cholangiocarcinoma.

Organic-Inorganic Hybrid Interfaces Enable the Preparation of Nitrogen-Doped Hollow Carbon Nanospheres as High-Performance Anodes for Lithium and Potassium-Ion Batteries.

An abundant hollow nanostructure is crucial for fast Li+ and K+ diffusion paths and sufficient electrolyte penetration, which creates a highly conductive network for ionic and electronic transport. In this study, we successfully developed a molecular-bridge-linked, organic-inorganic hybrid interface that enables the preparation of in situ nitrogen-doped hollow carbon nanospheres. Moreover, the prepared HCNSs, with high nitrogen content of up to 10.4%, feature homogeneous and regular morphologies. The resulting HCNSs exhibit excellent lithium and potassium storage properties when used as electrode materials. Specifically, the HCNS-800 electrode demonstrates a stable reversible discharge capacity of 642 mA h g-1 at 1000 mA g-1 after 500 cycles for LIBs. Similarly, the electrode maintains a discharge capacity of 205 mA h g-1 at 100 mA g-1 after 500 cycles for KIBs. Moreover, when coupled with a high-mass-loading LiFePO4 cathode to design full cells, the HCNS-800‖LiFePO4 cells provide a specific discharge capacity of 139 mA h g-1 at 0.1 C. These results indicate that the HCNS electrode has promising potential for use in high-energy and environmentally sustainable lithium-based and potassium-based batteries.

High-efficient capture and degradation of formaldehyde based on the electric-field-enhanced catalytic effect.

Enhancing the generation of active groups is of great significance for alleviating the catalyst deactivation of formaldehyde (HCHO) by accelerating the decomposition of intermediate products. Herein, an electric-field-enhanced catalytic effect was proposed for the efficient capture and degradation of HCHO base on carbon cloth loaded manganese oxide catalyst (MnOx-CC). Under the action of electric field, MnOx can generate more hydroxyl radicals (•OH) and superoxide radicals (•O2-), thus accelerating the degradation of HCHO and intermediates at room temperature. After the introduction electric field (∼1 ×104 V/m), •O2- and •OH radical on the surface of MnOx-CC catalyst can be increased by 8 times and 23 times, respectively. At weight hourly space velocity of 300,000 mL/(gcat h) for ∼15 ppm HCHO, MnOx-CC-Electric Field catalyst reached the removal efficiency of 99.4%, and the CO2 conversion efficiency of 81.2%, without decrease significantly within 80 h. Theoretical calculation shows that the electric field can increase the electron state density of Mn atom at the Fermi level and reduce the adsorption energy of HCHO, O2 and H2O, thus promoting the generation of active groups and degradation of intermediate products. The electric-field-enhancement catalytic effect provides a new approach for the degradation of Volatile Organic Compounds.

Amino acids can deplete ATP and impair nitric oxide detoxification by Escherichia coli.

Nitric oxide (·NO) is a prevalent antimicrobial that is known to damage iron-containing enzymes in amino acid (AA) biosynthesis pathways. With Escherichia coli, ·NO is detoxified in aerobic environments by Hmp, which is an enzyme that is synthesized de novo in response to ·NO. With this knowledgebase, it is expected that the availability of AAs in the extracellular environment would enhance ·NO detoxification, because AAs would foster translation of Hmp. However, we observed that ·NO detoxification by E. coli was far slower in populations grown and treated in the presence of AAs (AA+) in comparison to those grown and stressed in the absence of AAs (AA-). Further experiments revealed that AA+ populations had difficulty translating proteins under ·NO stress, and that ·NO activated the stringent response in AA+ populations. Additional work revealed significant ATP depletion in ·NO-stressed AA+ cultures that far exceeded that of ·NO-stressed AA- populations. Transcription, translation, and RelA were not found to be significant contributors to the ATP depletion observed, whereas AA import was implicated as a significant ATP consumption pathway. Alleviating ATP depletion while maintaining access to AAs partially restored ·NO detoxification, which suggested that ATP depletion contributed to the translational difficulties observed in ·NO-stressed AA+ populations. These data reveal an unexpected interaction within the ·NO response network of E. coli that stimulates a stringent response by RelA in conditions where AAs are plentiful.

Access to 3-Aminomethylated Maleimides via a Phosphine-Catalyzed Aza-Morita-Baylis-Hillman Type Coupling.

A designed method for the preparation of 3-aminomethylated maleimides via Morita-Baylis-Hillman (MBH) reaction was developed. This phosphine-catalyzed coupling adopted maleimides and 1,3,5-triazinanes as the substrate, giving a series of 3-aminomethylated maleimide derivatives with a double bond retained on the maleimide ring in 41-90% yield. Acylation, isomerization, and Michael addition of the obtained products demonstrated the synthetic application of the present protocol. The results of control experiments indicated that phosphorus ylide formation and elimination take place during the reaction pathway.

Amphiphilic Nano-Swords for Direct Penetration and Eradication of Pathogenic Bacterial Biofilms.

Bacterial biofilms are major causes of persistent and recurrent infections and implant failures. Biofilms are formable by most clinically important pathogens worldwide, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, causing recalcitrance to standard antibiotic therapy or anti-biofilm strategies due to amphiphilic impermeable extracellular polymeric substances (EPS) and the presence of resistant and persistent bacteria within the biofilm matrix. Herein, we report our design of an oligoamidine-based amphiphilic "nano-sword" with high structural compacity and rigidity. Its rigid, amphiphilic structure ensures effective penetration into EPS, and the membrane-DNA dual-targeting mechanism exerts strong bactericidal effect on the dormant bacterial persisters within biofilms. The potency of this oligoamidine is shown in two distinct modes of application: it may be used as a coating agent for polycaprolactone to fully inhibit surface biofilm growth in an implant-site mimicking micro-environment; meanwhile, it cures model mice of biofilm infections in various ex vivo and in vivo studies.

Adsorption-enhanced catalytic oxidation for long-lasting dynamic degradation of organic dyes by porous manganese-based biopolymeric catalyst.

Improving the adsorption kinetics of metal-oxide catalysts is critical for the enhancement of catalytic performance in heterogeneous catalytic oxidation reactions. Herein, based on the biopolymer pomelo peels (PP) and metal-oxide catalyst manganese oxide (MnOx), an adsorption-enhanced catalyst (MnOx-PP) was constructed for catalytic organic dyes oxidative-degradation. MnOx-PP shows excellent methylene blue (MB) and total carbon content (TOC) removal efficiency of 99.5 % and 66.31 % respectively, and keeps the long-lasting stable dynamic degradation efficiency during 72 h based on the self-built continuous single-pass MB purification device. The chemical structure similarity and negative-charge polarity sites of the biopolymer PP improve the adsorption kinetics of organic macromolecule MB, and construct the adsorption-enhanced catalytic oxidation microenvironment. Meanwhile, the adsorption-enhanced catalyst MnOx-PP obtains lower ionization potential and O2 adsorption energy to promote the continuous generation of active substance (O2*, OH*) for the further catalytic oxidation of adsorbed MB molecules. This work explored the adsorption-enhanced catalytic oxidation mechanism for the degradation of organic pollutants, and provided a feasible technical idea for designing adsorption-enhanced catalysts for the long-lasting efficient removal of organic dyes.

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice.

Psoriasis is an autoimmune disease, which has a significant impact on the quality of patient's life. And, there is still no cure for psoriasis. The human dental pulp stem cell (hDPSC) possesses the properties of immunoregulation. In this study, we aimed to determine the effect of hDPSC on the imiquimod (IMQ)-induced psoriasis in mice. The psoriasis model was established by topical application of IMQ cream in mice for 7 days. We found that subcutaneous injection of hDPSC could reduce the symptoms of skin lesions in IMQ-induced psoriasis and suppress the expression of keratin 16, S100A8, S100A9, which are associated with abnormal epidermal proliferation. Subepithelial inflammatory cytokines, CD4+ T lymphocytes and CD11c+ dendritic cells infiltrations were significantly inhibited in by hDPSC. The TNF-α, IFN-γ expressions in serum were decreased, and splenomegaly induced by IMQ was improved after hDPSC treatment. In summary, our study demonstrated that hDPSC could reduce the symptoms of skin lesions and suppress local and systemic immune responses of IMQ-induced psoriasis in mice, which might provide a new sight for the treatment of psoriasis.