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1.
Nat Commun ; 14(1): 443, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707540

RESUMO

In the unprecedented single-cell sequencing and spatial multiomics era of biology, fluorescence in situ hybridization (FISH) technologies with higher sensitivity and robustness, especially for detecting short RNAs and other biomolecules, are greatly desired. Here, we develop the robust multiplex π-FISH rainbow method to detect diverse biomolecules (DNA, RNA, proteins, and neurotransmitters) individually or simultaneously with high efficiency. This versatile method is successfully applied to detect gene expression in different species, from microorganisms to plants and animals. Furthermore, we delineate the landscape of diverse neuron subclusters by decoding the spatial distribution of 21 marker genes via only two rounds of hybridization. Significantly, we combine π-FISH rainbow with hybridization chain reaction to develop π-FISH+ technology for short nucleic acid fragments, such as microRNA and prostate cancer anti-androgen therapy-resistant marker ARV7 splicing variant in circulating tumour cells from patients. Our study provides a robust biomolecule in situ detection technology for spatial multiomics investigation and clinical diagnosis.

2.
Toxins (Basel) ; 15(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36668884

RESUMO

Aflatoxin is a potent mycotoxin and a common source of grain contamination that leads to great economic losses and health problems. Although distilled baijiu cannot be contaminated by aflatoxin, its presence in the brewing process affects the physiological activities of micro-organisms and reduces product quality. Bacillus cereus XSWW9 capable of degrading aflatoxin B1 (AFB1) was isolated from daqu using coumarin as the sole carbon source. XSWW9 degraded 86.7% of 1 mg/L AFB1 after incubation at 37 °C for 72 h and tolerated up to 1 mg/L AFB1 with no inhibitory effects. Enzymes in the cell-free supernatant of XSSW9 played a significant role in AFB1 degradation. The AFB1-degradation activity was sensitive to protease K and SDS treatment, which indicated that extracellular proteins were responsible for the degradation of AFB1. In order to investigate the AFB1-degradation ability of XSSW9 during the baijiu brewing process, AFB1 and XSWW9 were added to grain fermentation (FG-T) and normal grain fermentation without AFB1, while normal grain fermentation without AFB1 and XSWW9 was used as a control (FG-C). At the end of the fermentation, 99% AFB1 was degraded in the residue of fermented grains. The differences of microbial communities in the fermented grains showed that there were no significant differences between FG-T and FG-C in the relative abundance of dominant genera. The analysis of volatile compounds of their distillation showed that the contents of skeleton flavor components was similar between FG-T and FG-C. These results offer a basis for the development of effective strategies to reduce the effect of AFB1 on the brewing process and ensure that the production of baijiu is stable.


Assuntos
Aflatoxina B1 , Bacillus cereus , Bacillus cereus/metabolismo , Aflatoxina B1/metabolismo , Fermentação , Endopeptidase K , Biodegradação Ambiental
3.
Metabolites ; 13(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36677005

RESUMO

The hormone 20-hydroxyecdysone (20E) and the ecdysone receptors (ECR and USP) play critical roles in the growth and metabolism of insects, including honeybees. In this study, we investigated the effect of 20E on the growth and development of honeybee larvae by rearing them in vitro and found reduced food consumption and small-sized pupae with increasing levels of 20E. A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis of widely targeted metabolomics was used to examine the changes in the metabolites after an exogenous 20E application to honeybee larvae and the underlying mechanisms. A total of 374 different metabolites were detected between the control group and the 20E treatment group, covering 12 subclasses. The most significant changes occurred in 7-day-old larvae, where some monosaccharides, such as D-Glucose and UDP-galactose, were significantly upregulated. In addition, some metabolic pathways, such as glycolysis/gluconeogenesis and galactose metabolism, were affected by the 20E treatment, suggesting that the 20E treatment disrupts the metabolic homeostasis of honeybee larvae hemolymph and that the response of honeybee larvae to the 20E treatment is dynamic and contains many complex pathways. Many genes involved in carbohydrate metabolism, including genes of the glycolysis and glycogen synthesis pathways, were downregulated during molting and pupation after the 20E treatment. In contrast, the expression levels of the genes related to gluconeogenesis and glycogenolysis were significantly increased, which directly or indirectly upregulated glucose levels in the hemolymph, whereas RNA interference with the 20E receptor EcR-USP had an opposite effect to that of the 20E treatment. Taken together, 20E plays a critical role in the changes in carbohydrate metabolism during metamorphosis.

4.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677884

RESUMO

The well-defined heterostructure of the photocathode is desirable for photoelectrochemically producing hydrogen from aqueous solutions. Herein, enhanced heterostructures were fabricated based on typical stable covalent organic framework (TpPa-1) films and TiO2 nanotube arrays (NTAs) as a proof-of-concept model to tune the photoelectrochemical (PEC) hydrogen generation by tailoring the photoelectrode microstructure and interfacial charge transport. Ultrathin TpPa-1 films were uniformly grown on the surface of TiO2 NTAs via a solvothermal condensation of building blocks by tuning the monomer concentration. The Pt1@TpPa-1/TiO2-NTAs photoelectrode with single-atom Pt1 as a co-catalyst demonstrated improved visible-light response, enhanced photoconductance, lower onset potential, and decreased Tafel slope value for hydrogen evolution. The hydrogen evolution rate of the Pt1@TpPa-1/TiO2-NTAs photoelectrode was five times that of Pt1@TpPa-1 under AM 1.5 simulated sunlight irradiation and the bias voltage of 0 V. A lower overpotential was recorded as 77 mV@10 mA cm-2 and a higher photocurrent density as 1.63 mA cm-2. The hydrogen evolution performance of Pt1@TpPa-1/TiO2-NTAs photoelectrodes may benefit from the well-matched band structures, effective charge separation, lower interfacial resistance, abundant interfacial microstructural sites, and surficial hydrophilicity. This work may raise a promising way to design an efficient PEC system for hydrogen evolution by tuning well-defined heterojunctions and interfacial microstructures.

5.
Sci Total Environ ; : 161790, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36702267

RESUMO

Antimicrobial resistance (AMR) and pathogens derived from food animals and their associated environments have emerged as challenging threats to humans from a health perspective, but our understanding of these risks and their key prevention and control points in the current intensive breeding industry remains poor. By creating an integral composition and risk profile of the resistome and microbiome through metagenomics in feces, flies, dust, sewage, and soil along the four-stage laying hen production chain, we found that the whole production chain is a hotspot for antimicrobial resistance genes (ARGs) with 374 known subtypes and pathogens, including 157 human pathogenic bacteria (HPB). Feces and flies were identified as major risk sources for these contaminations. Also, we confirmed a twin-risk of AMR and pathogenicity prevailing throughout the chain, but with different frequencies in each stage; thus, high-risk ARGs in the young chicken stage and highly prioritized HPB in the chick stage contributed 37.33 % to the total AMR risk and 36.36 % to the pathogenic risks, respectively, thus rendering the two stages to be the key prevention points. Moreover, the prevalence of 112 binned ARG supercarriers (for example, Klebsiella pneumoniae harboring 20 ARGs) was unraveled along the production chain, especially in feces, flies, and dust, and 87 potential hosts exhibited high pathogenic risk, high-risk AMR, or both, with 262 ARGs and 816 virulence factor genes. Overall, this study provides first-hand comprehensive data on high-risk ARGs and their pathogenic hosts in the intensive laying hen production chain, and thus is fundamentally important for developing new measures to help control the global AMR crisis induced through the animal-environment-human pathway.

6.
J Agric Food Chem ; 71(3): 1562-1576, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36630317

RESUMO

This study investigated the effects of sesamolin on kidney injury, intestinal barrier dysfunction, and gut microbiota imbalance in high-fat and high-fructose (HF-HF) diet-fed mice and explored the underlying correlations among them. The results indicated that sesamolin suppressed metabolic disorders and increased renal function parameters. Histological evaluation showed that sesamolin mitigated renal epithelial cell degeneration and brush border damage. Meanwhile, sesamolin inhibited the endotoxin-mediated induction of the Toll-like receptor 4-related IKKα/NF-κB p65 pathway activation. Additionally, sesamolin mitigated intestinal barrier dysfunction and improved the composition of gut microbiota. The correlation results further indicated that changes in the dominant phyla, including Firmicutes, Deferribacterota, Desulfobacterota, and Bacteroidota, were more highly correlated with a reduction in endotoxemia and metabolic disorders, as well as decreases in intestinal proinflammatory response and related renal risk biomarkers. The results of this study suggest that sesamolin attenuates kidney injuries, which might be associated with its effects on the reduction of endotoxemia and related metabolic disorders through the restoration of the intestinal barrier and the modulation of gut microbiota. Thus, sesamolin may be a potential dietary supplement for protection against obesity-associated kidney injury.


Assuntos
Endotoxemia , Microbioma Gastrointestinal , Enteropatias , Animais , Camundongos , Endotoxemia/metabolismo , Frutose/efeitos adversos , Dieta , Rim/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
7.
J Hematol Oncol ; 16(1): 1, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600307

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética
8.
Clin Epidemiol ; 15: 73-89, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36659903

RESUMO

Purpose: We sought to develop and validate an incident non-small cell lung cancer (NSCLC) algorithm for United States (US) healthcare claims data. Diagnoses and procedures, but not medications, were incorporated to support longer-term relevance and reliability. Methods: Patients with newly diagnosed NSCLC per Surveillance, Epidemiology, and End Results (SEER) served as cases. Controls included newly diagnosed small-cell lung cancer and other lung cancers, and two 5% random samples for other cancer and without cancer. Algorithms derived from logistic regression and machine learning methods used the entire sample (Approach A) or started with a previous algorithm for those with lung cancer (Approach B). Sensitivity, specificity, positive predictive values (PPV), negative predictive values, and F-scores (compared for 1000 bootstrap samples) were calculated. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives. Results: The best performing algorithm utilized neural networks (Approach B). A 10-variable point-score algorithm was derived from logistic regression (Approach B); sensitivity was 77.69% and PPV = 67.61% (F-score = 72.30%). This algorithm was less sensitive for patients ≥80 years old, with Medicare follow-up time <3 months, or missing SEER data on stage, laterality, or site and less specific for patients with SEER primary site of main bronchus, SEER summary stage 2000 regional by direct extension only, or pre-index chronic pulmonary disease. Conclusion: Our study developed and validated a practical, 10-variable, point-based algorithm for identifying incident NSCLC cases in a US claims database based on a previously validated incident lung cancer algorithm.

9.
J Colloid Interface Sci ; 637: 67-75, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36682119

RESUMO

Traditional self-polishing antifouling coatings kill surface organisms by releasing toxic substances, which are damaging to the ecosystem. As a natural antimicrobial substance, eugenol is environmentally friendly and has been proven by different research teams to be effective in enhancing the anti-fouling effect of coatings in the real sea. While in these previous research works, the eugenol was released directly into the seawater thus cannot further serve as surface antifouling effect, leading to a limited antifouling effect of the coating. In this work, the quaternary ammonium component was introduced into the butyl ester-based resin - poly (eugenol methacrylate - acryloyloxyethyltrimethyl ammonium chloride - hexafluorobutyl methacrylate - methyl methacrylate - butyl methacrylate - ethylene glycol methyl ether acrylate) (EMQFP) coating for the first time by simple one-step free radical polymerization method. On the one hand, the eugenol produced by hydrolysis is anchored to the quaternary ammonium on the coating surface for a period of time due to the cationic-π interaction, instead of being released into seawater immediately after hydrolysis, thus increasing the utilization rate of eugenol; on the other hand, the negatively charged carboxylate groups generated after hydrolysis in the coating are mutually attracted to quaternary ammonium through electrostatic effect, so the resin chain segment conformation on the coating surface adjusted to produce zwitterionic-like structure, and the hydration of zwitterionic inhibits primary fouling adhesion.

10.
Meat Sci ; 198: 109085, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36640716

RESUMO

To solve the problem of easy spoilage of chilled meat during storage, we fabricated a novel composite film using carboxymethyl chitosan (CMCS)/pullulan (Pul)/eugenol (E) by casting method. The results showed that the mechanical properties of the films were better when the CMCS/Pul ratio was 2.5/2.5. The Fourier transform infrared spectroscopy (FTIR) results showed that intermolecular hydrogen bonds were formed among E, CMCS, and Pul, which was consistent with the rheological test results. Scanning electron microscopic (SEM) images showed that eugenol was well dispersed in the CMCS/Pul matrix. The addition of eugenol significantly increased the antibacterial properties and antioxidant properties. Moreover, when 5% eugenol was added, the water vapor permeability (WVP) of the film reduced to 2.41 × 10-11 g/m·s·Pa. Finally, the freshness of the chilled meat wrapped with the eugenol-containing composite film was prolonged, thereby offering a potential alternative to synthetic materials.

11.
Chem Rev ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692900

RESUMO

Polymeric materials produced from fossil fuels have been intimately linked to the development of industrial activities in the 20th century and, consequently, to the transformation of our way of living. While this has brought many benefits, the fabrication and disposal of these materials is bringing enormous sustainable challenges. Thus, materials that are produced in a more sustainable fashion and whose degradation products are harmless to the environment are urgently needed. Natural biopolymers─which can compete with and sometimes surpass the performance of synthetic polymers─provide a great source of inspiration. They are made of natural chemicals, under benign environmental conditions, and their degradation products are harmless. Before these materials can be synthetically replicated, it is essential to elucidate their chemical design and biofabrication. For protein-based materials, this means obtaining the complete sequences of the proteinaceous building blocks, a task that historically took decades of research. Thus, we start this review with a historical perspective on early efforts to obtain the primary sequences of load-bearing proteins, followed by the latest developments in sequencing and proteomic technologies that have greatly accelerated sequencing of extracellular proteins. Next, four main classes of protein materials are presented, namely fibrous materials, bioelastomers exhibiting high reversible deformability, hard bulk materials, and biological adhesives. In each class, we focus on the design at the primary and secondary structure levels and discuss their interplays with the mechanical response. We finally discuss earlier and the latest research to artificially produce protein-based materials using biotechnology and synthetic biology, including current developments by start-up companies to scale-up the production of proteinaceous materials in an economically viable manner.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36659840

RESUMO

Monophosphoryl lipid A (MPL), mainly isolated from Salmonella minnesota R595, has been used as adjuvant in several vaccines. In this study, an Escherichia coli strain that can efficiently produce the MPL has been constructed. The gene clusters related to the biosynthesis of O-antigen, core oligosaccharide, enterobacterial common antigen, and colanic acid were sequentially removed to save the carbon source and to increase the activity of PagP in E. coli MG1655. Then, the genes pldA, mlaA, and mlaC related to the phospholipid transport system were further deleted, resulting in the strain MW012. Finally, the genes lpxE from Francisella novicida and pagP and pagL from Salmonella were overexpressed in MW012 to modify the structure of lipid A, resulting in the strain MW012/pWEPL. Lipid A species were isolated from MW012/pWEPL and analyzed by thin-layer chromatography and liquid chromatography-mass spectrometry. The results showed that mainly two MPL species were produced in E. coli MW012/pWEPL, one is hexa-acylated, and the other is penta-acylated. More importantly, the proportion of the hexa-acylated MPL, which is the most effective component of lipid A vaccine adjuvant, reached 75%. E. coli MW012/pWEPL constructed in this study provided a good alternative for the production of lipid A vaccine adjuvant MPL.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36673793

RESUMO

This systematic review and meta-analysis aimed to systematically evaluate the effect of physical activity (PA) on inhibitory function in children with ADHD. Experimental studies on the effect of PA on the inhibitory function of children with ADHD were retrieved. The data were obtained from PubMed, The Cochrane Library, Web of Science, EBSCO (MEDLINE, APA Psyclnfo, ERIC), Embase, Scopus, and ProQuest. The search period was from the date of inception of the respective databases to 4 May 2022, and Reviewer Manager software (version 5.3) was used for analysis. Eleven articles and 713 samples were included in the meta-analysis. Results revealed that PA can significantly improve the inhibitory function of children with ADHD (SMD = 0.78, 95% CI: 0.45-1.10, p < 0.001). Subgroup analysis showed that the effectiveness of PA as an intervention in improving the inhibitory function of children with ADHD was moderated by the frequency, intensity, duration, type, and length of intervention. Based on the findings, PA can effectively improve interference suppression inhibitory function in children with ADHD. Longitudinal open-skill exercise for 60 min or more, two times/week has the best effect on improving inhibitory function in children with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Criança , Exercício Físico
15.
Cell Res ; 33(1): 55-70, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36588115

RESUMO

Microphthalmia transcription factor (MITF) regulates melanocyte development and is the "lineage-specific survival" oncogene of melanoma. MITF is essential for melanoma initiation, progression, and relapse and has been considered an important therapeutic target; however, direct inhibition of MITF through small molecules is considered impossible, due to the absence of a ligand-binding pocket for drug design. Here, our structural analyses show that the structure of MITF is hyperdynamic because of its out-of-register leucine zipper with a 3-residue insertion. The dynamic MITF is highly vulnerable to dimer-disrupting mutations, as we observed that MITF loss-of-function mutations in human Waardenburg syndrome type 2 A are frequently located on the dimer interface and disrupt the dimer forming ability accordingly. These observations suggest a unique opportunity to inhibit MITF with small molecules capable of disrupting the MITF dimer. From a high throughput screening against 654,650 compounds, we discovered compound TT-012, which specifically binds to dynamic MITF and destroys the latter's dimer formation and DNA-binding ability. Using chromatin immunoprecipitation assay and RNA sequencing, we showed that TT-012 inhibits the transcriptional activity of MITF in B16F10 melanoma cells. In addition, TT-012 inhibits the growth of high-MITF melanoma cells, and inhibits the tumor growth and metastasis with tolerable toxicity to liver and immune cells in animal models. Together, this study demonstrates a unique hyperdynamic dimer interface in melanoma oncoprotein MITF, and reveals a novel approach to therapeutically suppress MITF activity.


Assuntos
Melanoma , Microftalmia , Animais , Humanos , Fatores de Transcrição/metabolismo , Microftalmia/genética , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Regulação da Expressão Gênica , Proteínas Oncogênicas/genética , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
16.
Plant Physiol ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36617228

RESUMO

Glandular trichomes are universal epidermal structures that produce abundant specialized metabolites. However, knowledge of the initiation of glandular heads in glandular trichomes is limited. Herein, we found an intrinsic link of morphogenesis between glandular trichomes and non-glandular trichomes. Two novel homeodomain leucine zipper (HD-Zip) Ⅳ members in tobacco (Nicotiana tabacum), NtHD9 and NtHD12, played important roles in long glandular trichome formation: NtHD9 was responsible for glandular head formation, while NtHD12 simultaneously controlled the formation of stalks and glandular heads. DAP-seq analysis suggested that NtHD9 can bind to the KKGCATTWAWTR motif of the cytochromes P450 94C1 (NtCYP94C1) promoter, which is involved in jasmonoyl-isoleucine oxidation. RNA-seq analysis of non-transformed tobacco and nthd9 plants revealed that NtHD9 modulates the expression of jasmonate (JA) signaling- and six trichome development related genes. Notably, MeJA treatment restored the morphogenesis of long glandular trichomes in nthd9 and nthd12 plants, and the size of glandular heads increased with increasing MeJA concentration. However, the phenotype of long glandular trichome absence in double mutants of NtHD9 and NtHD12 could not be restored by MeJA. Our data demonstrate that NtHD9 and NtHD12 have distinct major functions yet overlapping roles in long glandular trichome formation via JA signaling.

17.
Exp Ther Med ; 25(1): 59, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36588818

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide and the consumption of a high-calorie diet is one of its risk factors. Calorie restriction (CR) slows tumor growth in a variety of cancers, including colorectal cancer; however, the mechanism behind this remains unknown. In the present study, CR effectively reduced the tumor volume and weight in a xenograft BALB/c male nude mouse model. In addition, tumor immunohistochemistry revealed that the CR group had significantly higher expression of Bax (P<0.001) and significantly lower levels of Bcl2 (P<0.0001) and Ki67 (P<0.001) compared with control group. Furthermore, data from 16S ribosomal (r)RNA sequencing implied that CR was able to reprogram the microbiota structure, characterized by increased Lactobacillus constituent ratio (P<0.05), with amelioration of microbial dysbiosis caused by CRC. Further receiver operating characteristic curves demonstrated that the bacteria Bacteroides [area under the curve (AUC)=0.800], Lactobacillus (AUC=0.760) and Roseburia (AUC=0.720) served key roles in suppression of CRC in the mouse model. The functional prediction of intestinal flora indicated 'cyanoamino acid metabolism' (P<0.01), 'replication initiation protein REP (rolling circle plasmid replication)' (P<0.01), 'tRNA G10 N-methylase Trm11' (P<0.01) and 'uncharacterized protein with cyclophilin fold, contains DUF369 domain' (P<0.05) were downregulated in CR group. These findings implied that CR suppressed CRC in mice and altered the gut microbiota.

18.
ACS Appl Mater Interfaces ; 15(2): 2985-2995, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36622791

RESUMO

It is extremely challenging to significantly increase the voltaic efficiency, power density, and cycle stability of a Zn-air battery by just adjusting the catalytic performance of the cathode with nanometers/atomistic engineering because of the restriction of thermodynamic equilibrium potential. Herein, inspired by solar batteries, the S-atom-bridged FeNi particles and N-doped hollow carbon nanosphere composite configuration (FeNi-S,N-HCS) is presented as a prototype of muti-functional air electrode material (intrinsic electrocatalytic function and additional photothermal function) for designing photoresponsive all-solid-state Zn-air batteries (PR-ZABs) based on the photothermal effect. The local temperature of the FeNi-S,N-HCS electrode can well respond to the stimuli of sunlight irradiation because of their superior photothermal effect. As expected, under illumination, the power density of the as-fabricated PR-ZABs based on the FeNi-S,N-HCS electrode can be improved from 77 mW cm-2 to 126 mW cm-2. Simultaneously, charge voltage can be dramatically reduced, and cycle lifetime is also prolonged under illumination, because of the expedited electrocatalytic kinetics, the increased electrical conductivity, and the accelerated desorption rate of O2 bubbles from the electrode. By exerting the intrinsic electrocatalytic and photothermal efficiency of the electrode materials, this research paves new ways to improve battery performance from kinetic and thermodynamic perspectives.

19.
Eur J Med Chem ; 247: 115053, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36587419

RESUMO

Herein 2-cyanoethoxy-N,N,N',N'-tetraisopropyl-phosphorodiamidite(10, PIII, 3.5 eq.) could synergistically react with 3',5'-dihydroxyl groups in a dinucleotide(PV) at the cyclization step for the synthesis of cyclic dinucleotides (CDNs) (c-di-GMP, cGAMP etc.) and their phosphorothioated analogues. A dynamic PIII-PV coordination mechanism has been proposed for the cyclization procedure which is confirmed by the variant 31P NMR data and molecular simulation. Among the mono-phosphorothioated CDNs, two stereoisomers showed different capacity for STING activation and the reason was predicted by molecular modeling. While compound 12b1 showed most potent ability to elicit cytokines (IFNß, IL-6, Cxcl9 and Cxcl10) induction compared to another stereoisomer. Also, 12b1 significantly inhibited the tumor growth in the EO771 model with both 0.1 µg (i.t.) and 2 µg (i.v.) administration through the aid of a Mix delivery system developed by our group, and achieved a 31% long-term survival rate of tumor-bearing mice. 12b1/Mix significantly improved the percentage of CD8+ or CD4+ effector memory T (Tem, CD44highCD62Llow) cells and CD8+ central memory T (Tcm, CD44highCD62Lhigh) cells in the blood of EO771 mice, inducing the immune memory against EO771 tumor cells. Relatively lower dose regimens of 12b1(0.1 µg)/Mix displayed better tumor suppression by more potent STING pathway activation and higher levels of cytokines induction in the tumor.


Assuntos
Citocinas , Neoplasias , Animais , Camundongos , Lipídeos , Nucleotídeos de Citosina/química , Nucleotídeos de Citosina/metabolismo
20.
Immunotherapy ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36628567

RESUMO

Trousseau's syndrome is a relatively rare reported event in immunotherapy-related clinical trials, mostly occurring in the early period of immune checkpoint inhibitor (ICI) therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. The patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.


In clinical practice, symptoms associated with abnormal coagulation or fibrinolytic function in malignant tumors are known as Trousseau's syndrome. Its main clinical features include cerebral infarction, myocardial infarction, peripheral arterial embolism, etc. Trousseau's syndrome is a relatively rare reported event in immune checkpoint inhibitors (ICIs)-related clinical studies, mostly occurring in the early period of ICI therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab, one of the ICI agents, maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. This patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.

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