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BACKGROUND: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. METHODS: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. RESULTS: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. CONCLUSIONS: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.
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Purpose: The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG. Methods: PLWH's basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA <50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96. Results: 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/µL (IQR 420.5-758) to 642 cells/µL (IQR 466.5-854) at week 96 (p<0.0001). An improvement was observed in liver function (ALT: p<0.0001; AST: p<0.0001) and fasting glucose (p<0.0001). However, there was an elevation in creatinine (Cr) (p<0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p<0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen. Conclusion: This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.
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Entropy engineering is widely proven to be effective in achieving ultra-low thermal conductivity for well-performed thermoelectric and heat management applications. However, no strong correlation between entropy and lattice thermal conductivity is found until now, and the fine-tuning of thermal conductivity continuously via entropy-engineering in a wide entropy range is still lacking. Here, a series of high-entropy layered semiconductors, Ni1- x(Fe0.25Co0.25Mn0.25Zn0.25)xPS3, where 0 ≤ x < 1, with low mass/size disorder is designed. High-purity samples with mixing configuration entropy of metal atomic site in a wide range of 0-1.61R are achieved. Umklapp phonon-phonon scattering is found to be the dominating phonon scattering mechanism, as revealed by the linear T-1 dependence of thermal conductivity. Meanwhile, fine tuning of the lattice thermal conductivity via continuous entropy engineering at metal atomic sites is achieved, in an almost linear dependence in middle-/high- entropy range. Moreover, the slope of the κ - T-1 curve reduces with the increase in entropy, and a linear response of the reduced Grüneisen parameter is revealed. This work provides an entropy engineering strategy by choosing multiple metal elements with low mass/size disorder to achieve the fine tuning of the lattice thermal conductivity and the anharmonic effect.
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A novel donor/acceptor carbene intermediate has been developed using diaryldiazoketones as carbene precursors. In the presence of the chiral dirhodium catalyst, Rh2(S-TPPTTL)4, diaryldiazoketones undergo highly regio-, stereo-, and diastereoselective C-H functionalization of activated and unactivated secondary and tertiary C-H bonds. Computational studies revealed that the arylketo group behaves differently than the carboxylate acceptor group because the orientation of the arylketo group predetermines which face of the carbene will be attacked.
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The red imported fire ant (Solenopsis invicta Buren) is one of the 100 worst invasive alien species in the world. At present, the control of red imported fire ants is still mainly based on chemical control, and the most commonly used is indoxacarb bait. In this study, the contact and feeding toxicity of 16 kinds of nanomaterials to workers, larvae, and reproductive ants were evaluated after 24 h, 48 h, and 72 h. The results showed that the mortality of diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes among workers reached 98.67%, 97.33%, and 68%, respectively, after contact treatment of 72 h. The mortality of both larval and reproductive ants was less than 20% after 72 h of treatment. All mortality rates in the fed treatment group were below 20% after 72 h. Subsequently, we evaluated the digging, corpse-removal, and foraging behaviors of workers after feeding with diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes for 24 h, which yielded inhibitory effects on the behavior of red imported fire ants. The most effective was diatomite, which dramatically decreased the number of workers that dug, extended the time needed for worker ant corpse removal and foraging activities, decreased the number of workers that foraged, and decreased the weight of the food carried by the workers. In addition, we also evaluated the contact and feeding toxicity of these three nanomaterials in combination with indoxacarb on red imported fire ants. According to contact toxicity, after 12 h of contact treatment, the death rate among the red imported fire ants exposed to the three materials combined with indoxacarb reached more than 97%. After 72 h of exposure treatment, the mortality rate of larvae was more than 73% when the nanomaterial content was above 1% and 83% when the diatomite content was 0.5%, which was significantly higher than the 50% recorded in the indoxacarb control group. After 72 h of feeding treatment, the mortality of diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes combined with indoxacarb reached 92%, 87%, and 98%, respectively. The death rates of the three kinds of composite ants reached 97%, 67%, and 87%, respectively. The three kinds of composite food had significant inhibitory effects on the behavior of workers, and the trend was largely consistent with the effect of nanomaterials alone. This study provides technical support for the application of nanomaterials in red imported fire ant control.
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The rational design of efficient bifunctional single-atom electrocatalysts for industrial water splitting and the comprehensive understanding of its complex catalytic mechanisms remain challenging. Here, we report a Ni single atoms supported on oxygen-incorporated Mo2C via Ni-O-Mo bridge bonds, that gives high oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) bifunctional activity. By ex situ synchrotron X-ray absorption spectroscopy and electron microscopy, we found that after HER, the coordination number and bond lengths of Ni-O and Ni-Mo (Ni-O-Mo) were all altered, yet the Ni species still remain atomically dispersed. In contrast, after OER, the atomically dispersed Ni were agglomerated into very small clusters with new Ni-Ni (Ni-O-Ni) bonds appeared. Combining experimental results and DFT calculations, we infer the oxidation degree of Mo2C and the configuration of single-atom Ni are both vital for HER or OER. This study provides both a feasible strategy and model to rational design highly efficient electrocatalysts for water electrolysis.
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Solenopsis invicta, often known as the red imported fire ants (RIFAs), is a well-known global invasive ant species that can be found in agricultural, urban, and natural environments worldwide. Simultaneously, it also inhabits the soil. Biochar is generated by the pyrolysis of organic matter under high-temperature anoxic environments and widely used in agricultural ecosystems and soil amendment. However, to date, it remains unknown as to whether soil application of biochar has a negative effect on RIFAs. In our study, we investigated the toxicity and irritability effects of different amounts of biochar (0%, 1%, 2%, 5%, 10%, and 20%) introduced into the soil on red fire ants; upon comparison with the control soil (0% biochar), the application of 1%, 2%, and 5% biochar did not result in significantly different results. But the utilization of biochar at a concentration over 10% effectively repelled the RIFAs, resulting in their departure from the treated soils. High doses of biochar were able to cause death of red fire ants; the mortality rate of red fire ants reached 55.56% after 11 days of 20% biochar treatment. We also evaluated the effects of biochar on four behaviors of red fire ants, namely aggregation, walking, grasping, and attacking; 20% of the biochar treatment group reduced aggregation by 64.22% and this value was 55.22%, 68.44%, and 62.36% for walking, grasping, and attacking. Finally, we measured the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activity and malondialdehyde (MDA) content in red fire ants; the results showed that the activities of the three enzymes increased with the increase in biochar addition, which indicated that a high dose of biochar induced oxidative stress in red fire ants. Our results indicate that biochar has the potential to cause toxicity and repel red imported fire ants (RIFAs) in a manner that is dependent on the concentration. We propose that biochar could be utilized in the control and manufacturing of baits for red fire ant management. This work establishes a foundation for the prevention and management of red fire ants and the logical utilization of biochar.
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This manuscript describes the development of the first diastereoselective intermolecular synthesis of alkyl ethers via reductive etherification of diverse ketones or aldehydes with alcohols. Key to this development was the use of low-temperature high-throughput experimentation (HTE) technologies that enabled rapid reaction optimizations and parallel synthesis. A broad scope of pharmaceutically relevant substrates was surveyed, which formed alkyl ethers effectively. In addition, we demonstrated that the diastereoselectivity of this transformation can be readily modulated by prudent selection of the reductant.
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The rhodium-catalyzed enantioselective C-H functionalization of unactivated C-H bonds by means of donor/acceptor carbene-induced C-H insertion was extended to substrates containing nitrogen functionality. The rhodium-stabilized donor/acceptor carbenes were generated by rhodium-catalyzed decomposition of aryldiazoacetates. The phthalimido group was the optimum nitrogen protecting group. C-H functionalization at the most sterically accessible methylene site was achieved using Rh2(S-2-Cl-5-BrTPCP)4 as catalyst, whereas Rh2(S-TPPTTL)4 was the most effective catalyst for C-H functionalization at tertiary C-H bonds and for the desymmetrization of N-phthalimidocyclohexane.
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Rodio , Estructura Molecular , Rodio/química , Estereoisomerismo , Catálisis , FtalimidasRESUMEN
The red imported fire ant (RIFA), Solenopsis invicta Buren (Hymenoptera: Formicidae), is an invasive species that is considered to be among the 100 most dangerous species to human health and the environment. RIFA is currently controlled primarily by chemical insecticides. However, human health concerns and environmental problems require environment friendly, green insect pest control technology. In this study, the HS-SPME-GC/MS method was used to determine the volatile components of six essential oils, namely Illicium verum Burm, Blumea balsamifera (L.) DC., Citrus limon Burm, Acorus tatarinowii Schott, Mosla chinensis Maxim, and Cinnamomum cassia Presl, as well as their fumigation activity against RIFA. D-Limonene was identified as a core volatile in all six essential oils. The effects of volatile substances from essential oils on the fumigation activity and behavior of RIFA workers were studied by closed fumigation method. Except for C. limon essential oil, all other five plant essential oils exhibit excellent fumigation activity under the treatment of a concentration at 10 µL/ cm3 within 24 h. All plant essential oils are capable of causing the death of all red fire ants, while C. limon essential oil exhibited the lowest fumigation activity at 63.25%. Significant reductions in RIFA aggregation, aggressiveness, and gripping abilities were observed with all plant essential oils, and antenna sensilla appeared to bend or break. Moreover, after treating red ant fire ants with essential oil for 24 h, three protective enzyme activities were assessed. All six plant essential oils were shown to have enhanced enzyme activities for superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT). It has been shown that plant essential oils have the capability of reducing the viability of red fire ants via receptor and behavioral factors, ultimately causing them to die off. As a conclusion, plant oils were demonstrated to be negatively affecting RIFA and providing a green and environmentally sustainable control method in this study.
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Hormigas , Insecticidas , Aceites Volátiles , Animales , Humanos , Aceites Volátiles/farmacología , Insecticidas/farmacología , Control de Insectos , Aceites de Plantas/farmacologíaRESUMEN
There are many problems that result from the use of a large number of chemical pesticides to control plant diseases, including pathogenic bacteria resistance, environmental contamination, and human health effects. Recently, endophytic fungi have become a significant source of bioactive fungicide products and an invaluable resource for excavating microbial pesticides. In this study, endophytic fungi with biocontrol potential were isolated and screened from Mikania micrantha leaves, stems, and roots. Fifty endophytic fungi were isolated and their antagonistic activity was studied in vitro using the confrontation culture method. The J2-3 strains from stems exhibit broad-spectrum and high activity. The strain's biological characteristics were determined by various culture conditions, and it was identified as Fusarium proliferatum by both morphological and ITS sequence analysis. Biological characteristics of the J2-3 strain were also tested. The optimum temperature for mycelium growth and sporulation was 25 °C and 30 °C, respectively. For mycelium growth, starch was the optimum carbon source, and peptone was the optimum nitrogen source for sucrose, mycelium growth, and sporulation. Mycelium growth was killed by a temperature of 60 °C, and sporulation was killed by a temperature of 55 °C. The light aided mycelium growth, and the light alternated between light and dark cycles for sporulation. Further, pot experiments were conducted to determine the antagonistic and viable effects of highly antagonistic strains on cucumber. The spore suspension's final control efficacy on cucumber wilt disease was up to 62.79% and it also promoted cucumber growth significantly. The results show that the entophytic fungus J2-3 from M. micrantha can protect cucumbers from wilt disease and promote growth.
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Cucumis sativus , Fusarium , Plaguicidas , Humanos , Cucumis sativus/microbiología , Hongos , Plaguicidas/farmacología , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiologíaRESUMEN
Cu single-atom catalysts (Cu SACs) have been considered as promising catalysts for efficient electrocatalytic CO2 reduction reactions (ECRRs). However, the reports on Cu SACs with an asymmetric atomic interface to obtain CO are few. Herein, we rationally designed two Cu SACs with different asymmetric atomic interfaces to explore their catalytic performance. The catalyst of CuN3O/C delivers high ECRR selectivity with an FECO value of above 90% in a wide potential window from -0.5 to -0.9 V vs RHE (in particular, 96% at -0.8 V), while CuCO3/C delivers poor selectivity for CO production with a maximum FECO value of only 20.0% at -0.5 V vs RHE. Besides, CuN3O/C exhibited a large turnover frequency (TOF) up to 2782.6 h-1 at -0.9 V vs RHE, which is much better than the maximum 4.8 h-1 of CuCO3/C. Density functional theory (DFT) results demonstrate that the CuN3O site needs a lower Gibbs free energy than CuCO3 in the rate-determining step of CO desorption, leading to the outstanding performance of CuN3O/C on the process of ECRR-to-CO. This work provides an efficient strategy to improve the selectivity and activity of the ECRR via regulating asymmetric atomic interfaces of SACs by adjusting the coordination atoms.
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BACKGROUND: mRNA vaccines are emerging as new targets for cancer immunotherapy. However, the potential tumor antigens for mRNA vaccine design in hepatocellular carcinoma (HCC) remain to be elucidated. METHODS: Genetic and RNA-Seq data were obtained from TCGA and ICGC. Tumor-specific antigens (TSAs) were identified by differential expression, mutation status, HLA binding, antigen-presenting cell (APC) correlation, immune checkpoint (ICP) relevance and prognosis. Consensus clustering was used for patient classification. The molecular and immune status of TSAs and clustered patients, including prognostic ability, tumor microenvironment, tumor-related signature and tumor immune dysfunction and exclusion (TIDE), were further characterized. RESULTS: Five dysregulated and mutated TSAs were identified in HCC (TSA5): FXYD6, JAM2, GALNT16, C7, and CCDC146. Seven immune gene modules and five immune subtypes (IS1-IS5) of HCC were identified. The immune subtypes and TSA5-related modules showed distinct molecular, cellular and clinical characteristics. According to our study, IS1 patients may be suitable for vaccination.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Antígenos de Neoplasias/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , ARN Mensajero/genética , Microambiente Tumoral , Vacunas de ARNmRESUMEN
An electrochemical, nickel-catalyzed reductive coupling of alkylpyridinium salts and aryl halides is reported. High-throughput experimentation (HTE) was employed for rapid reaction optimization and evaluation of a broad scope of pharmaceutically relevant structurally diverse aryl halides, including complex drug-like substrates. In addition, the transformation is compatible with both primary and secondary alkylpyridinium salts with distinct conditions. Mechanistic insights were critical to enhance the efficiency of coupling using secondary alkylpyridinium salts. Systematic comparisons of the electrochemical and non-electrochemical methods revealed the complementary scope and efficiency of the two approaches.
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Autophagy plays a critical role in tumor pathogenesis. However, autophagy-related signature in Hepatocellular carcinoma (HCC) has not been revealed yet. We quantified the levels of various cancer hallmarks and identified ATG101 as the major risk factor for overall survival in HCC. A robust ATG101-related gene signature (ATS) for prognosis was constructed using a combination of bioinformatic and statistical approaches. Additionally, genetic and immunological properties were measured between ATS-high and ATS-low groups. The ATS signature was associated with shortened overall survival in HCC patients independently of clinicopathological characteristics. ATS status defines an inflamed yet exhausted tumor microenvironment, in which the activities of the exhausted CD8+ or CD4+ T cells were strongly associated with ATS. The ATS signature predicts the drug resistance to the immunotherapy, thus a combination of targeted therapy and immunotherapy might be suitable for ATS-high patients. This work shed light on the function of ATG101-related genes in HCC and revealed that the ATS signature may be a useful prognostic biomarker for differentiating molecular and immunological features and predicting probable response to the therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Biomarcadores de Tumor/genética , Estimación de Kaplan-Meier , Pronóstico , Microambiente Tumoral/genética , Proteínas Relacionadas con la Autofagia/genética , Proteínas de Transporte VesicularRESUMEN
Here, Ru clusters supported on nitrogen-doped hollow carbon spheres show a remarkable activity and durability toward the hydrogen oxidation reaction (HOR) and H2-O2 fuel cell performance in alkaline media. Theoretical simulations indicate that Ru clusters endow a thermodynamically favourable HOR kinetics and an optimal hydrogen adsorption affinity.
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Finding agriculturally active compounds from nature or finding active lead compounds from natural products, artificial synthesis and structural modification are the main ways to create new agrochemical. In order to explore the agricultural activities of Chonemorpha splendens Chun et Tsiang (C.â splendens), an important medicinal plant, the antioxidant activities and allelopathic potential were investigated. C.â splendens was extracted with methanol, then, C.â splendens methanol extract (CSME) were extracted with petroleum ether, chloroform, ethyl acetate and butanol. Reducing activity, lipid peroxidation, and the scavenging abilities for DPPHâ , O2 -. , HOâ , and H2 O2 were also measured and allelopathic potentials were evaluated by bioassay method. GC/MS analysis revealed that esters were the main component (66.34 %) of CSME, the total CSME flavonoid content was 313â mg g-1 (rutin equivalent). The chloroform phase of CSME was identified as stigmasterol by NMR for the first time. The DPPHâ scavenging rate of CSME was 87 %, with an IC50 value of 0.12±0.02â mg mL-1 , which was significantly difference from the positive control, Trolox. Chloroform fraction showed the strongest inhibitory effect against Mimosa pudica (MP) seed germination at 1.0â mg mL-1 (100 % inhibition), which was better than that of the chemical herbicide paraquat. In the seed growth experiment, systematic EC50 and the principal component analysis (PCA) were used to assess the allelopathic potential of extracts. The systematic EC50 values of Crotalaria pallida Ait. (CP), Bidens pilosa L. (BP) were significantly greater than MP. MP, Oryza sativa L. (OS) and Lactuca satiua L., (LS) inhibited all parameters. Our results would provide an idea for controlling weeds through allelopathy from C.â splendens to reduce dependency on synthetic herbicides.