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2.
Article de Anglais | MEDLINE | ID: mdl-39377608

RÉSUMÉ

Covalent-organic frameworks (COFs) are promising electrocatalysts for the selective synthesis of H2O2 through the two-electron oxygen reduction reaction (2e- ORR). However, the design and synthesis of efficient and stable COF-based electrocatalysts is still challenging. In this work, a predesigned 1,10-phenanthroline-based one-dimensional COF (PYTA-PTDE-COF) was constructed to anchor main group metal (In, Sn, and Sb) as electrocatalysts toward 2e- ORR. The catalysts are featured with fully exposed metalated side chains. Structural characterization revealed that PYTA-PTDE-M's (M = In, Sn, and Sb) are all quite similar, except for the coordinated metal ions with the maintenance of good crystallinity. They all exhibited satisfying activity and selectivity toward 2e- ORR under alkaline conditions. Among them, PYTA-PTDE-Sb exhibited the best performance (Eonset is 0.765 V, the H2O2 selectivity is 96%, and the yield rate is 209.2 mmol gcat-1 h-1). Moreover, it also delivered superior stability with almost no attenuation of current density during the long-time test. Theoretical calculations revealed that the Sb metal site in the COFs has the lowest adsorption strength of *OOH, which could be the main reason for its superior selectivity. The PYTA-PTDE-Sb assembled zinc-air battery realizes not only the supply of clean energy but also the production of green chemicals, showing it is highly promising in practical applications. This work offers an example for designing main group metal-coordinated 1D COFs and reveals fundamental structure-activity relationship toward 2e- ORR.

3.
Cell Commun Signal ; 22(1): 448, 2024 Sep 26.
Article de Anglais | MEDLINE | ID: mdl-39327550

RÉSUMÉ

Immunotherapy has emerged as a highly effective treatment for various tumors. However, the variable response rates associated with current immunotherapies often restrict their beneficial impact on a subset of patients. Therefore, more effective treatment approaches that can broaden the scope of therapeutic benefits to a larger patient population are urgently needed. Studies have shown that some parasites and their products, for example, Plasmodium, Toxoplasma, Trypanosoma, and Echinococcus, can effectively transform "cold" tumors into "hot" battlefields and reshape the tumor microenvironment, thereby stimulating innate and adaptive antitumor immune responses. These parasitic infections not only achieve the functional reversal of innate immune cells, such as neutrophils, macrophages, myeloid-derived suppressor cells, regulatory T cells, and dendritic cells, in tumors but also successfully activate CD4+/CD8+ T cells and even B cells to produce antibodies, ultimately resulting in an antitumor-specific immune response and antibody-dependent cellular cytotoxicity. Animal studies have confirmed these findings. This review discusses the abovementioned content and the challenges faced in the future clinical application of antitumor treatment strategies based on parasitic infections. With the potential of these parasites and their byproducts to function as anticancer agents, we anticipate that further investigations in this field could yield significant advancements in cancer treatment.


Sujet(s)
Immunothérapie , Tumeurs , Humains , Immunothérapie/méthodes , Tumeurs/immunologie , Tumeurs/thérapie , Animaux , Parasites/immunologie , Microenvironnement tumoral/immunologie
4.
J Agric Food Chem ; 72(40): 22063-22072, 2024 Oct 09.
Article de Anglais | MEDLINE | ID: mdl-39318349

RÉSUMÉ

While frequently used herbicides display limited efficacy against herbicide-resistant weeds, it becomes imperative to explore novel herbicides that ensure both effective weed management and environmental safety. Though 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitory herbicides like mesotrione are prevalent in maize weed management, their integration into rice production is hindered due to the inherent sensitivity of rice HPPD (OsHPPD). In this study, a mutant allele of OsHPPD featuring six amino acid substitutions, termed OsHPPD-6M, maintains enzymatic activity in 200 µm mesotrione while the wild type can only withstand 1 µm. Enzymatic assays in vitro indicated that the HPPD activity of OsHPPD-6M surpassed that of the WT by 2-fold through enhanced substrate-binding. Its overexpression in transgenic rice conferred greater tolerance to mesotrione, topramezone, and isoxaflutole by 36.7-, 41.6-, and 37.1-fold relative to that in the WT rice. Interestingly, these 6M-OE plants demonstrated substantially elevated contents of carotenoids compared to WT plants without a significant impact on agronomic traits.


Sujet(s)
4-hydroxyphenylpyruvate dioxygenase , Caroténoïdes , Résistance aux herbicides , Herbicides , Oryza , Protéines végétales , Végétaux génétiquement modifiés , Oryza/génétique , Oryza/métabolisme , Oryza/enzymologie , Oryza/composition chimique , 4-hydroxyphenylpyruvate dioxygenase/génétique , 4-hydroxyphenylpyruvate dioxygenase/métabolisme , 4-hydroxyphenylpyruvate dioxygenase/antagonistes et inhibiteurs , 4-hydroxyphenylpyruvate dioxygenase/composition chimique , Protéines végétales/génétique , Protéines végétales/métabolisme , Protéines végétales/composition chimique , Herbicides/pharmacologie , Herbicides/composition chimique , Herbicides/métabolisme , Résistance aux herbicides/génétique , Végétaux génétiquement modifiés/génétique , Végétaux génétiquement modifiés/métabolisme , Végétaux génétiquement modifiés/composition chimique , Caroténoïdes/métabolisme , Mutagenèse , Antienzymes/pharmacologie , Antienzymes/composition chimique , Cyclohexanones/pharmacologie , Cyclohexanones/composition chimique , Cyclohexanones/métabolisme , Mauvaises herbes/génétique , Mauvaises herbes/effets des médicaments et des substances chimiques , Mauvaises herbes/métabolisme , Mauvaises herbes/enzymologie
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124765, 2024 Dec 05.
Article de Anglais | MEDLINE | ID: mdl-39018670

RÉSUMÉ

Excessive use of gentamicin sulfate can cause severe nephrotoxicity and ototoxicity, abnormal levels of Fe3+ intake can also cause serious damage to body. Therefore, establishing a fast and accurate detection method for the above-mentioned substances is of great significance. However, traditional detection methods such as high-performance liquid chromatography still have certain problems such as high cost and complex operation. Fluorescent MOFs are favored by analysts due to their high specific surface area, high porosity, adjustable pore size, and good stability. In this paper, we have synthesized four rare earth MOFs based on the pyridinecarboxylic acid ligand (H2L), which are [Eu(L)1/2H2O]n, [Gd(L)1/2H2O]n, [Sm(L)1/2H2O]n, [Y(L)3/2H2O·DMF]n. The structures of four MOFs were confirmed by single crystal X-ray diffraction, which proved that MOF-1, MOF-2 and MOF-3 were isostructural, and all the four MOFs were three-dimensional structures. In the fluorescence test, gentamicin sulfate and Fe3+ can cause significant fluorescence quenching of MOF-1 and MOF-4 respectively, and show good selectivity and anti-interference performance, as well as low detection limit and wide detection range. This work may provide a possibility for the detection of gentamicin sulfate and iron ions in complex environments.

6.
BioDrugs ; 38(5): 681-689, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39080181

RÉSUMÉ

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).


Sujet(s)
Anticorps monoclonaux humanisés , Eczéma atopique , Humains , Eczéma atopique/traitement médicamenteux , Adulte , Mâle , Femelle , Anticorps monoclonaux humanisés/usage thérapeutique , Anticorps monoclonaux humanisés/effets indésirables , Adulte d'âge moyen , Résultat thérapeutique , Indice de gravité de la maladie , Jeune adulte , Sous-unité alpha du récepteur à l'interleukine-4/antagonistes et inhibiteurs
7.
Stress Health ; 40(5): e3454, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39078475

RÉSUMÉ

Depression is closely related to individual social functions. The current study aimed to examine whether depression is associated with ostracism, whether interpretation bias mediates this relationship, and whether trait mindfulness moderates direct and indirect relationships between depression and ostracism. Overall, 389 Chinese college students completed the Center for Epidemiological Survey, Depression Scale, Interpretation Bias Questionnaire, Philadelphia mindfulness scale, and perceived ostracism scale at two-time points. Latent Profile analysis and moderated mediation analysis were performed. After controlling for sex and age, depression (t1) was positively correlated to perceived ostracism, with this relationship being partially mediated by negative interpretation bias (IBN, t2). The effect of IBN on perceived ostracism was weak when awareness was high at time 2. Acceptance had a non-significant moderating role in the relationship between IBN and perceived ostracism at time 2. LPA delineated three profiles: high awareness, high acceptance, and medium mindfulness. The moderating role of the different profiles in the relationship between IBN (t2) and perceived ostracism (t2) was significant. Depressed individuals appear to experience more ostracism because of IBN. Awareness might alleviate the effect of IBN on perceived ostracism.


Sujet(s)
Conscience immédiate , Dépression , Pleine conscience , Étudiants , Humains , Femelle , Mâle , Étudiants/psychologie , Jeune adulte , Dépression/psychologie , Adulte , Universités , Isolement social/psychologie , Adolescent , Enquêtes et questionnaires , Chine
8.
Polymers (Basel) ; 16(14)2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-39065289

RÉSUMÉ

A polysaccharide (CP2-S), consisting of glucose with a weight average molecular weight of 5.9 × 106, was purified from the fruit bodies of Cordyceps militaris. In this work, the corresponding structure and anti-tumor activity in vivo were investigated. Methylation and NMR analysis revealed that CP2-S was composed of a →4)-α-D-Glcp-(1→ backbone with partial substitution occurring at O-6 by T-linked α-D-Glcp in every ten residues, which has not been reported in previous reports. In vivo anti-tumor experiments showed that CP2-S could inhibit the growth of Lewis lung carcinoma in mice. Tumor inhibition rates were 17.8%, 24.5%, and 29.5% at dosages of 12.5, 50, and 100 mg/kg/d, respectively. Compared with the cisplatin group, mice treated with CP2-S exhibited a significant increase in spleen index (increased 22.7-42.4%) and thymus index (increased 47.7-36.8%). Additionally, serum levels of IgM and IgG in tumor-bearing mice increased by approximately 6.11~10.75-folds and 1.31~1.38-folds, respectively. These findings prove that CP2-S significantly inhibited the growth of Lewis lung carcinoma through immune-enhancing activity in mice.

9.
Opt Lett ; 49(13): 3701-3704, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38950246

RÉSUMÉ

We presented the first, to our knowledge, demonstration of an ultraviolet (UV) laser at 223.8 nm by six-harmonic generation of an electro-optic Q-switched cavity dumping 1342 nm Nd:YVO4 laser. It offers high power, constant short pulse duration, and adjustable pulse repetition rate. The pulse duration is independent of the pump power and repetition rate compared to classical Q-switched oscillators. The output efficiency of the UV laser is optimized by adjusting the focusing lens. With the incident pump power of 30 W, an maximum average output power of 249 mW was obtained at 13 kHz. The pulse width maintained 3.4-3.5 ns from 5 to 20 kHz. The maximum pulse energy of 28.1 µJ was obtained at 5 kHz, and the corresponding peak power was up to 8.1 kW.

10.
Nat Microbiol ; 9(8): 1979-1992, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38862603

RÉSUMÉ

Dimethylsulfoniopropionate (DMSP) is an abundant marine organosulfur compound with roles in stress protection, chemotaxis, nutrient and sulfur cycling and climate regulation. Here we report the discovery of a bifunctional DMSP biosynthesis enzyme, DsyGD, in the transamination pathway of the rhizobacterium Gynuella sunshinyii and some filamentous cyanobacteria not previously known to produce DMSP. DsyGD produces DMSP through its N-terminal DsyG methylthiohydroxybutyrate S-methyltransferase and C-terminal DsyD dimethylsulfoniohydroxybutyrate decarboxylase domains. Phylogenetically distinct DsyG-like proteins, termed DSYE, with methylthiohydroxybutyrate S-methyltransferase activity were found in diverse and environmentally abundant algae, comprising a mix of low, high and previously unknown DMSP producers. Algae containing DSYE, particularly bloom-forming Pelagophyceae species, were globally more abundant DMSP producers than those with previously described DMSP synthesis genes. This work greatly increases the number and diversity of predicted DMSP-producing organisms and highlights the importance of Pelagophyceae and other DSYE-containing algae in global DMSP production and sulfur cycling.


Sujet(s)
Phylogenèse , Composés de sulfonium , Composés de sulfonium/métabolisme , Cyanobactéries/génétique , Cyanobactéries/métabolisme , Cyanobactéries/enzymologie , Methyltransferases/métabolisme , Methyltransferases/génétique , Protéines bactériennes/métabolisme , Protéines bactériennes/génétique , Voies de biosynthèse/génétique
11.
Front Psychol ; 15: 1281207, 2024.
Article de Anglais | MEDLINE | ID: mdl-38899122

RÉSUMÉ

Anthropomorphism, the attribution of human-like qualities (e.g., mental states) to nonhuman entities, is a universal but variable psychological experience. Adults with professionally diagnosed autism or high levels of subclinical autistic traits consistently show greater tendencies to anthropomorphize, which has been hypothesized to reflect 1) a compensatory mechanism for lack of social connectedness and 2) a persistence of childhood anthropomorphism into adulthood. Here, we directly tested these hypotheses in a general population sample consisting of both adults (N=685, 17-58 years old) and early adolescents (N=145, 12-14 years old) using the refined 9-item Anthropomorphism Questionnaire (AnthQ9), which measures both present and childhood anthropomorphic tendencies. We found that adults with heightened autistic traits reported increased present anthropomorphism (e.g., tend more to perceive computers as having minds), which held even after controlling for social connectedness. In contrast, adolescents with heightened autistic traits did not show increased present anthropomorphism, but rather reported reduced childhood anthropomorphism (e.g., less likely to perceive toys as having feelings) after controlling for social connectedness. We also found evidence that the present and childhood subscales of the AnthQ9 may tap into fundamentally different aspects of anthropomorphism. The results suggest that increased anthropomorphic tendencies in adults with heightened autistic traits cannot be explained solely by increased sociality motivation, but may be due to delayed development of anthropomorphism, although alternative possibilities of measurement problems cannot be ruled out. Implications for the measurement of anthropomorphism and its relation with theory of mind were also discussed.

12.
Molecules ; 29(11)2024 May 30.
Article de Anglais | MEDLINE | ID: mdl-38893439

RÉSUMÉ

Hydrogen peroxide (H2O2) is an environmentally friendly oxidant with a wide range of applications, and the two-electron pathway (2e-) of the oxygen reduction reaction (ORR) for H2O2 production has attracted much attention due to its eco-friendly nature and operational simplicity in contrast to the conventional anthraquinone process. The challenge is to design electrocatalysts with high activity and selectivity and to understand their structure-activity relationship and catalytic mechanism in the ORR process. Covalent organic frameworks (COFs) provide an efficient template for the construction of highly efficient electrocatalysts due to their designable structure, excellent stability, and controllable porosity. This review firstly outlines the design principles of COFs, including the selection of metallic and nonmetallic active sites, the modulation of the electronic structure of the active sites, and the dimensionality modulation of the COFs, to provide guidance for improving the production performance of H2O2. Subsequently, representative results are summarized in terms of both metallic and metal-free sites to follow the latest progress. Moreover, the challenges and perspectives of 2e- ORR electrocatalysts based on COFs are discussed.

13.
Front Pharmacol ; 15: 1374182, 2024.
Article de Anglais | MEDLINE | ID: mdl-38783959

RÉSUMÉ

Lung cancer has high metastasis and drug resistance. The prognosis of lung cancer patients is poor and the patients' survival chances are easily neglected. Ferroptosis is a programmed cell death proposed in 2012, which differs from apoptosis, necrosis and autophagy. Ferroptosis is a novel type of regulated cell death which is driven by iron-dependent lipid peroxidation and subsequent plasma membrane ruptures. It has broad prospects in the field of tumor disease treatment. At present, multiple studies have shown that biological compounds can induce ferroptosis in lung cancer cells, which exhibits significant anti-cancer effects, and they have the advantages in high safety, minimal side effects, and less possibility to drug resistance. In this review, we summarize the biological compounds used for the treatment of lung cancer by focusing on ferroptosis and its mechanism. In addition, we systematically review the current research status of combining nanotechnology with biological compounds for tumor treatment, shed new light for targeting ferroptosis pathways and applying biological compounds-based therapies.

14.
J Agric Food Chem ; 72(21): 12029-12044, 2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38752706

RÉSUMÉ

Weeds present a significant challenge to agricultural productivity, and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides have proven to be effective in managing weed populations in rice fields. To develop ACCase-inhibiting herbicide-resistant rice, we generated mutants of rice ACCase (OsACC) featuring Ile-1792-Leu or Gly-2107-Ser substitutions through ethyl methyl sulfonate (EMS) mutagenesis. The Ile-1792-Leu mutant displayed cross-resistance to aryloxyphenoxypropionate (APP) and phenylpyrazoline (DEN) herbicides, whereas the Gly-2107-Ser mutants primarily exhibited cross-resistance to APP herbicides with diminished resistance to the DEN herbicide. In vitro assays of the OsACC activity revealed an increase in resistance to haloxyfop and quizalofop, ranging from 4.84- to 29-fold in the mutants compared to that in wild-type. Structural modeling revealed that both mutations likely reduce the binding affinity between OsACC and ACCase inhibitors, thereby imparting resistance. This study offers insights into two target-site mutations, contributing to the breeding of herbicide-resistant rice and presenting alternative weed management strategies in rice cultivation.


Sujet(s)
Acetyl-coA carboxylase , Antienzymes , Résistance aux herbicides , Herbicides , Mutation , Oryza , Protéines végétales , Acetyl-coA carboxylase/génétique , Acetyl-coA carboxylase/antagonistes et inhibiteurs , Acetyl-coA carboxylase/métabolisme , Acetyl-coA carboxylase/composition chimique , Oryza/génétique , Oryza/enzymologie , Herbicides/pharmacologie , Herbicides/composition chimique , Résistance aux herbicides/génétique , Protéines végétales/génétique , Protéines végétales/métabolisme , Protéines végétales/composition chimique , Protéines végétales/antagonistes et inhibiteurs , Antienzymes/pharmacologie , Antienzymes/composition chimique , Mauvaises herbes/effets des médicaments et des substances chimiques , Mauvaises herbes/génétique , Mauvaises herbes/enzymologie
15.
Arab J Gastroenterol ; 25(2): 150-159, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38719664

RÉSUMÉ

BACKGROUND AND STUDY AIMS: The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes. PATIENTS/MATERIAL AND METHODS: mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database. RESULTS: Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (p < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (p < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (p < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (p < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC. CONCLUSION: NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.


Sujet(s)
Tumeurs colorectales , Cellules tueuses naturelles , Humains , Tumeurs colorectales/génétique , Tumeurs colorectales/immunologie , Tumeurs colorectales/anatomopathologie , Cellules tueuses naturelles/immunologie , Pronostic , Mutation , Taux de survie , Analyse de survie , Régulation de l'expression des gènes tumoraux , Femelle , Mâle , Analyse de profil d'expression de gènes/méthodes
16.
Mar Pollut Bull ; 202: 116258, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38493606

RÉSUMÉ

Arsenic (As) is an abundant metalloid in marine environments, while the biogeochemical cycling of As in cold seeps remains poorly understood. We characterized the speciation of As and investigated controls of As distribution in cold seeps of South China Sea. High methane concentrations (0.2-5.5 mmol/L) and rapid sulfate depletion were observed in the seepage. Dissolved inorganic arsenic (DIAs) was enriched in the porewater ranging from 7.5 to 23.5 µg/L. As in the solid phase ranged from 2.9 to 22.6 µg/g, and sulfide mineral-bound As dominated the total arsenic (TAs) pool, followed by iron (manganese, aluminum) oxide-bound As. The significant correlations between porewater Fe2+ and DIAs reflect the controls of iron on DIAs release. Incubation experiments showed that adsorption to the solid phase and sulfate reduction activity affected the bioavailability and removal of DIAs, suggesting that multiple processes regulate the speciation and transformation of As in seep sediments.


Sujet(s)
Arsenic , Surveillance de l'environnement , Sédiments géologiques , Polluants chimiques de l'eau , Sédiments géologiques/composition chimique , Arsenic/analyse , Polluants chimiques de l'eau/analyse , Chine , Eau de mer/composition chimique
17.
Data Brief ; 53: 110183, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38406249

RÉSUMÉ

DNA-dependent protein kinase catalytic subunit (DNA-PK) is a multifunctional serine­threonine protein kinase that plays roles in non-homologous end joining of DNA repair in cells. NU7441 is a specific DNA-PKcs inhibitor. We investigated the effects of NU7441 on the transcriptome of BT549 triple negative breast cancer cells. Total RNA extracted from NU7441-treated or control BT549 cells was processed for preparation of sequencing libraries. Assessment of read quality was performed using fastqc tool. Trimming and filtering low-quality reads were performed using fastp. Reads were aligned by hisat2. SAM files were converted to BAM files using Samtools. The gene differential expression analysis, Gene Ontology (GO) analysis and KEGG pathway analysis were performed. After NU7441 treatment, total number of 2045 differential genes were selected according to |log2(FoldChange)| >= 1 & padj<= 0.05, among which 1365 genes were down-regulated and 680 genes were up-regulated. The differential expression genes in pattern recognition receptors (PRRs) immune responses signals, including NOD-like receptor signaling, Toll-like receptor signaling, RIG-I-like receptor signaling and cytosolic DNA-sensing pathways were noted in this paper.

18.
Carbohydr Polym ; 330: 121829, 2024 Apr 15.
Article de Anglais | MEDLINE | ID: mdl-38368108

RÉSUMÉ

The herbal medicine Polygonatum cyrtonema is highly regarded in China for its medicinal and dietary properties. However, further research is needed to elucidate the structure of its polysaccharide and understand how it promotes human health by modulating the gut microbiota. This study aims to investigate a homogeneous polysaccharide (PCP95-1-1) from Polygonatum cyrtonema and assess its susceptibility to digestion as well as its utilization by intestinal microbiota. The results confirmed that PCP95-1-1 is an agavin-type fructan, which possesses two fructose chains, namely ß-(2 â†’ 6) and ß-(2 â†’ 1) fructosyl-fructose, attached to the sucrose core, and has branches of ß-D-Fruf residues. Moreover, PCP95-1-1 demonstrated resistance to digestion and maintained its reducing sugar content throughout the digestive system, indicating it could reach the gut without being digested. In vitro fermentation of PCP95-1-1 significantly decreased the pH value (p < 0.05) while notably increasing the production of short-chain fatty acids (SCFAs), confirming its utilization by human gut microbiota. Additionally, PCP95-1-1 exhibited a significant ability (p < 0.05) to beneficial bacteria such as Megamonas and Bifidobacterium, while reducing the presence of facultative or conditional pathogens such as Escherichia-Shigella and Klebsiella at the genus level. Consequently, PCP95-1-1 has the potential to positively influence physical well-being by modulating the gut microbiota environment and can be developed as a functional food.


Sujet(s)
Microbiome gastro-intestinal , Polygonatum , Humains , Fructanes/pharmacologie , Polygonatum/composition chimique , Polyosides , Fructose
19.
Br J Dermatol ; 191(3): 336-343, 2024 Aug 14.
Article de Anglais | MEDLINE | ID: mdl-38366639

RÉSUMÉ

BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. CONCLUSIONS: Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.


Psoriasis is a skin disease characterized by scaly and raised patches of skin on any part of the body. The condition can be caused by a combination of how a person's immune system works, their genes and their environment. A cytokine is a substance secreted by certain cells of the immune system that have an effect on other cells. One such cytokine, called IL-17A, has been associated with different inflammatory diseases, including psoriasis. We conducted a large trial in Chinese people with moderate-to-severe psoriasis to look at the efficacy (ability to produce the intended result) and safety of a medicine called xeligekimab (known as a 'monoclonal antibody') which works by targeting IL-17A. We randomly assigned 420 Chinese patients to receive 200 mg of xeligekimab every 2 weeks or a 'placebo' (no active medicine) for the first 12 weeks. We extended the treatment schedule of xeligekimab to every 4 weeks for a further 40 weeks. To assess how the medicine worked, we measured people's psoriasis symptoms and severity. To assess how safe the medicine was, we looked at the side-effects (or 'adverse events'). The results of this trial showed that xeligekimab improved people's psoriasis and itching starting at week 4 of receiving treatment, and more than 60% of people achieved improvement or remission by week 6, which was sustained up to week 52. The safety of xeligekimab was similar to another medicine classed as a monoclonal antibody (called secukinumab) and there were no new or unexpected adverse events reported. Overall, our findings suggest that xeligekimab is a safe and effective medicine for the treatment of psoriasis in Chinese people.


Sujet(s)
Anticorps monoclonaux humanisés , Psoriasis , Humains , Psoriasis/traitement médicamenteux , Mâle , Méthode en double aveugle , Anticorps monoclonaux humanisés/effets indésirables , Anticorps monoclonaux humanisés/administration et posologie , Femelle , Adulte d'âge moyen , Adulte , Résultat thérapeutique , Produits dermatologiques/effets indésirables , Produits dermatologiques/usage thérapeutique , Produits dermatologiques/administration et posologie , Calendrier d'administration des médicaments , Interleukine-17/antagonistes et inhibiteurs , Indice de gravité de la maladie , Sujet âgé , Jeune adulte
20.
Front Behav Neurosci ; 18: 1332760, 2024.
Article de Anglais | MEDLINE | ID: mdl-38333761

RÉSUMÉ

Pain, a universal and burdensome condition, influences numerous individuals worldwide. It encompasses sensory, emotional, and cognitive facets, with recent research placing a heightened emphasis on comprehending pain's impact on emotion and cognition. Cognitive bias, which encompasses attentional bias, interpretation bias, and memory bias, signifies the presence of cognitive distortions influenced by emotional factors. It has gained significant prominence in pain-related research. Human studies have shown that individuals experiencing pain exhibit cognitive bias. Similarly, animal studies have demonstrated cognitive bias in pain-induced states across various species and disease models. In this study, we aimed to investigate the memory bias displayed by rats experiencing acute pain, using the affective bias test (ABT) as a tool and administering either hotplate or formalin to induce acute pain. Our data showed that rats demonstrated a significant preference for the control treatment-related substrate over the substrate associated with formalin treatment (p < 0.001), an indication of the prominent memory bias stimulated by acute formalin injections. However, when exposed to substrates related to hotplate treatment and control treatment, the acute pain induced by the hotplate treatment failed to generate a statistically significant choice bias in rats (p = 0.674). Our study demonstrates that the negative emotions associated with acute pain can be reflected by memory bias in ABT, at least for formalin-induced acute pain. This finding will augment our comprehension of the emotional and cognitive aspects of acute pain.

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