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1.
MAbs ; 16(1): 2374607, 2024.
Article de Anglais | MEDLINE | ID: mdl-38956880

RÉSUMÉ

Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding activity method, which incorporates both binding affinity and binding response and allows us to determine relative binding activity of antibodies with high accuracy and precision. We applied the SPR-based relative binding activity method in multiple forced degradation studies of antibody developability assessment. The current developability assessment strategy provided comprehensive, precise characterization of antibody binding activity in the stability studies, enabling us to perform correlation analysis and establish the structure-function relationship between relative binding activity and quality attributes. The impact of a given quality attribute on binding activity could be confidently determined without isolating antibody variants. We identified several potential CQAs, including Asp isomerization, Asn deamidation, and fragmentation. Some potential CQAs affected binding affinity of antibody and resulted in a reduction of binding activity. Certain potential CQAs impaired antibody binding to antigen and led to a loss of binding activity. A few potential CQAs could influence both binding affinity and binding response and cause a substantial decrease in antibody binding activity. Specifically, we identified low abundance Asn33 deamidation in the light chain complementarity-determining region as a potential CQA, in which all the stressed antibody samples showed Asn33 deamidation abundances ranging from 4.2% to 27.5% and a mild binding affinity change from 1.76 nM to 2.16 nM.


Sujet(s)
Anticorps monoclonaux , Résonance plasmonique de surface , Résonance plasmonique de surface/méthodes , Humains , Anticorps monoclonaux/composition chimique , Anticorps monoclonaux/immunologie , Affinité des anticorps , Liaison aux protéines , Animaux
2.
Sci Total Environ ; 946: 174187, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38936741

RÉSUMÉ

Nutrient requirement for crop growth, defined as the amount of nutrient that crops take up from soil to produce a specific grain yield, is a key parameter in determining fertilizer application rate. However, existing studies primarily focus on identifying nitrogen (N), phosphorus (P), and potassium (K) requirements solely in relation to grain yield, neglecting grain protein content, a crucial index for wheat grain quality. Addressing this gap, we conducted multi-site, multi-cultivar, and multi-year field trials across three ecological regions of China from 2016 to 2020 to elucidate variations in nutrient requirements for grain yield and grain protein. The research findings revealed that wheat grain yield ranged from 4.1 to 9.3 Mg ha-1 (average 6.9 Mg ha-1) and grain protein content ranged from 98 to 157 g kg-1 (average 127 g kg-1) across the three regions. Notably, the N requirement exhibited a nonlinear correlation with the wheat grain yield but a linear increase with increasing grain protein, while the P and K requirements positively correlated with grain yield and protein content. Regression models were formulated to determine the nutrient requirements (MENR), enabling the prediction of N, P, and K requirements for leading cultivars with varying grain yields and protein contents. Implementing nutrient requirements based on MENR projections resulted in substantial reductions in fertilizer rates: 22.0 kg ha-1 N (10.7 %), 9.9 kg ha-1 P (20.2 %), and 8.1 kg ha-1 K (16.3 %). This translated to potential savings of 0.4 Mt. N, 0.23 Mt. P, and 0.17 Mt. K, consequently mitigating 5.5 Mt. CO2 greenhouse-gas emission and yielding an economic benefit of 0.8 billion US$ annually in China. These findings underscore the significance of considering grain yield and protein content in estimating nutrient requirements for fertilizer recommendations to realize high-yielding, high-protein wheat production, and minimize overfertilization and associated environmental risks.

3.
Adv Mater ; : e2403223, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38896500

RÉSUMÉ

Incorporating passive radiative cooling and heating into personal thermal management has attracted tremendous attention. However, most current thermal management materials are usually monofunctional with a narrow temperature regulation range, and lack breathability, softness, and stretchability, resulting in a poor wearer experience and limited application scenarios. Herein, a breathable dual-mode leather-like nanotextile (LNT) with asymmetrical wrinkle photonic microstructures and Janus wettability for highly efficient personal thermal management is developed via a one-step electrospinning technique. The LNT is synthesized by self-bonding a hydrophilic cooling layer with welding fiber networks onto a hydrophobic photothermal layer, constructing bilayer wrinkle structures that offer remarkable optical properties, a wetting gradient, and unique textures. The resultant LNT exhibits efficient cooling capacity (22.0 °C) and heating capacity (22.1 °C) under sunlight, expanding the thermal management zone (28.3 °C wider than typical textiles). Additionally, it possesses favorable breathability, softness, stretchability, and sweat-wicking capability. Actual wearing tests demonstrate that the LNT can provide a comfortable microenvironment for the human body (1.6-8.0 °C cooler and 1.0-7.1 °C warmer than typical textiles) in changing weather conditions. Such a wearable dual-mode LNT presents great potential for personal thermal comfort and opens up new possibilities for all-weather smart clothing.

4.
Membranes (Basel) ; 14(6)2024 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-38921508

RÉSUMÉ

A membrane condenser (MC) is a novel membrane separation technology that utilizes the hydrophobic nature of porous membranes to capture water vapor from humid gas. Factors such as temperature, pressure, flow rate, and gas composition entering the membrane condenser play a crucial role in water recovery efficiency. This study utilized hydrophobic polytetrafluoroethylene (PTFE) hollow fiber membranes to create multiple identical membrane modules. This research investigated the impact of temperature, flow rate, pressure on the intake side, gas flow on the cooling side, membrane area, and other variables on the performance of the membrane condenser process. This study compared water extraction efficiency under different conditions, focusing on feed flow temperature and sweeping flow. Results showed that at a temperature of 60 °C, the water recovery rate was 24.7%, while a sweep gas flow rate of 4 L/min resulted in a recovery rate of 22.7%. The efficiency of the membrane condenser decreased with higher feed flow rates but increased with larger membrane areas. A proportional relationship between inlet flow and membrane area was observed, suggesting an optimal range of 0.51-0.67 cm/s for both parameters. These findings offer valuable insights for the practical implementation of hydrophobic membrane-based membrane condenser technology.

5.
Org Lett ; 26(26): 5472-5477, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38913068

RÉSUMÉ

Three dithio-fused boron dipyrromethenes (BODIPYs), DTFB-1, DTFB-2, and DTFB-3, in which symmetrically S-heteroaromatic ring units fused at [a], zigzag, and [b] bonds of the parent BODIPY core, respectively, were prepared from the facile and efficient post-functionalization of tetra-halogenated BODIPYs through Pd-catalyzed cyclization. Dithio-fusion at various positions of BODIPY effectively tunes their photophysical properties and single-crystal structural packing arrangements. The single-crystalline microribbons of DTFB-2 exhibit commendable hole mobilities in air, reaching up to 0.03 cm2 V-1 s-1.

7.
Appl Clin Genet ; 17: 71-84, 2024.
Article de Anglais | MEDLINE | ID: mdl-38835974

RÉSUMÉ

Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. Charcot-Marie-Tooth disease 4B1 (CMT4B1) is a rare subtype of CMT. CMT4B1 is an axonal demyelinating polyneuropathy with an autosomal recessive mode of inheritance. Patients with CMT4B1 usually manifested with dysfunction of the motor and sensory systems which leads to gradual and progressive muscular weakness and atrophy, starting from the peroneal muscles and finally affecting the distal muscles. Germline mutations in MTMR2 gene causes CMT4B1. Material and Methods: In this study, we investigated a 4-year-old Chinese boy with gradual and progressive weakness and atrophy of both proximal and distal muscles. The proband's parents did not show any abnormalities. Whole-exome sequencing and Sanger sequencing were performed. Results: Whole-exome sequencing identified a novel homozygous nonsense mutation (c.118A>T; p.Lys40*) in exon 2 of MTMR2 gene in the proband. This novel mutation leads to the formation of a truncated MTMR2 protein of 39 amino acids instead of the wild- type MTMR2 protein of 643 amino acids. This mutation is predicted to cause the complete loss of the PH-GRAM domain, phosphatase domain, coiled-coil domain, and PDZ-binding motif of the MTMR2 protein. Sanger sequencing revealed that the proband's parents carried the mutation in a heterozygous state. This mutation was absent in 100 healthy control individuals. Conclusion: This study reports the first mutation in MTMR2 associated with CMT4B1 in a Chinese population. Our study also showed the importance of whole-exome sequencing in identifying candidate genes and disease-causing variants in patients with CMT4B1.

8.
Front Cardiovasc Med ; 11: 1378655, 2024.
Article de Anglais | MEDLINE | ID: mdl-38826818

RÉSUMÉ

Primary myxofibrosarcoma of the heart, a rare cardiac malignancy, was diagnosed in a middle-aged female patient exhibiting progressive dyspnea following transthoracic echocardiography and pathological analysis. Postoperatively, the patient underwent chemotherapy and Lenvatinib mesylate therapy, with regular check-ups confirming her survival. After 10 months the patient is still alive and well.

9.
Front Microbiol ; 15: 1403964, 2024.
Article de Anglais | MEDLINE | ID: mdl-38903786

RÉSUMÉ

Beibu Gulf is an important semi-enclosed bay located in the northwestern South China Sea, and is famous for its high bio-productivity and rich bio-diversity. The fast development along the Beibu Gulf Economical Rim has brought pressure to the environment, and algal blooms occurred frequently in the gulf. In this study, surface water samples and micro-plankton samples (20-200 µm) were collected in the northern Beibu Gulf coast. Diversity and distribution of eukaryotic planktonic microalgae were analyzed by both metabarcoding and microscopic analyses. Metabarcoding revealed much higher diversity and species richness of microalgae than morphological observation, especially for dinoflagellates. Metabarcoding detected 144 microalgal genera in 8 phyla, while microscopy only detected 40 genera in 2 phyla. The two methods revealed different microalgal community structures. Dinoflagellates dominated in microalgal community based on metabarcoding due to their high copies of 18 s rRNA gene, and diatoms dominated under microscopy. Altogether 48 algal bloom and/or toxic species were detected in this study, 34 species by metabarcoding and 19 species by microscopy. Our result suggested a high potential risk of HABs in the Beibu Gulf. Microalgal community in the surface water samples demonstrated significantly higher OTU/species richness, alpha diversity, and abundance than those in the micro-plankton samples, although more HAB taxa were detected by microscopic observations in the micro-plankton samples. Furthermore, nano-sized taxa, such as those in chlorophytes, haptophytes, and chrysophyceans, occurred more abundantly in the surface water samples. This study provided a comprehensive morphological and molecular description of microalgal community in the northern Beibu Gulf.

10.
Environ Sci Technol ; 2024 Jun 28.
Article de Anglais | MEDLINE | ID: mdl-38943037

RÉSUMÉ

Although the impacts of exotic wetland plant invasions on native biodiversity, landscape features, and carbon-nitrogen cycles are well appreciated, biogeochemical consequences posed by ecological competition, such as the heterogeneity of dissolved organic matter (DOM) from plant detritus and its impact on the formation of reactive oxygen species, are poorly understood. Thus, this study delves into O2•- photogeneration potential of DOM derived from three different parts (stem, leaf, and panicle) of invasive Spartina alterniflora (SA) and native Phragmites australis (PA). It is found that DOM from the leaves of SA and the panicles of PA has a superior ability to produce O2•-. With more stable aromatic structures and a higher proportion of sulfur-containing organic compounds, SA-derived DOM generally yields more O2•- than that derived from PA. UVA exposure enhances the leaching of diverse DOM molecules from plant detritus. Based on the reported monitoring data and our findings, the invasion of SA is estimated to approximately double the concentration of O2•- in the surrounding water bodies. This study can help to predict the underlying biogeochemical impacts from the perspective of aquatic photochemistry in future scenarios of plant invasion, seawater intrusion, wetland degradation, and elevated solar UV radiation.

11.
Antib Ther ; 7(2): 177-186, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38933532

RÉSUMÉ

Cancer immunotherapy represents a paradigm shift in oncology, offering a superior anti-tumor efficacy and the potential for durable remission. The success of personalized vaccines and cell therapies hinges on the identification of immunogenic epitopes capable of eliciting an effective immune response. Current limitations in the availability of immunogenic epitopes restrict the broader application of such therapies. A critical criterion for serving as potential cancer antigens is their ability to stably bind to the major histocompatibility complex (MHC) for presentation on the surface of tumor cells. To address this, we have developed a comprehensive database of MHC epitopes, experimentally validated for their MHC binding and cell surface presentation. Our database catalogs 451 065 MHC peptide epitopes, each with experimental evidence for MHC binding, along with detailed information on human leukocyte antigen allele specificity, source peptides, and references to original studies. We also provide the grand average of hydropathy scores and predicted immunogenicity for the epitopes. The database (MHCepitopes) has been made available on the web and can be accessed at https://github.com/jcm1201/MHCepitopes.git. By consolidating empirical data from various sources coupled with calculated immunogenicity and hydropathy values, our database offers a robust resource for selecting actionable tumor antigens and advancing the design of antigen-specific cancer immunotherapies. It streamlines the process of identifying promising immunotherapeutic targets, potentially expediting the development of effective antigen-based cancer immunotherapies.

12.
Conserv Physiol ; 12(1): coae040, 2024.
Article de Anglais | MEDLINE | ID: mdl-38915852

RÉSUMÉ

The passive dissolution of anthropogenically produced CO2 into the ocean system is reducing ocean pH and changing a suite of chemical equilibria, with negative consequences for some marine organisms, in particular those that bear calcium carbonate shells. Although our monitoring of these chemical changes has improved, we have not developed effective tools to translate observations, which are typically of the pH and carbonate saturation state, into ecologically relevant predictions of biological risks. One potential solution is to develop bioindicators: biological variables with a clear relationship to environmental risk factors that can be used for assessment and management. Thecosomatous pteropods are a group of pelagic shelled marine gastropods, whose biological responses to CO2 have been suggested as potential bioindicators of ocean acidification owing to their sensitivity to acidification in both the laboratory and the natural environment. Using five CO2 exposure experiments, occurring across four seasons and running for up to 15 days, we describe a consistent relationship between saturation state, shell transparency and duration of exposure, as well as identify a suite of genes that could be used for biological monitoring with further study. We clarify variations in thecosome responses due to seasonality, resolving prior uncertainties and demonstrating the range of their phenotypic plasticity. These biomarkers of acidification stress can be implemented into ecosystem models and monitoring programmes in regions where pteropods are found, whilst the approach will serve as an example for other regions on how to bridge the gap between point-based chemical monitoring and biologically relevant assessments of ecosystem health.

13.
Transplant Direct ; 10(6): e1623, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38757052

RÉSUMÉ

Background: Vascularized composite allograft transplantation is a treatment option for complex tissue injuries; however, ischemia reperfusion injury and high acute rejection rates remain a challenge. Hypothermic machine perfusion using acellular storage perfusate is a potential solution. This study evaluated the University of Wisconsin Kidney Preservation Solution-1 (KPS-1) compared with normal saline (NS) for preservation of donor rat hindlimbs subjected to 24 h of ex vivo perfusion cold storage. Methods: Hindlimbs were subjected to 24-h perfusion cold storage with heparinized KPS-1 (n = 6) or heparinized NS (n = 6). Flow, resistance, and pH were measured continuously. At the end of the 24-h period, tissue was collected for histological analysis of edema and apoptosis. Results: KPS-1 perfused limbs showed significantly less edema than the NS group, as evidenced by lower limb weight gain (P < 0.001) and less interfascicular space (P < 0.001). KPS-perfused muscle had significantly less cell death than NS-perfused muscle based on terminal deoxynucleotidyl transferase dUTP nick-end labeling (P < 0.001) and cleaved caspase-3 staining (P = 0.045). During hypothermic machine perfusion, a significant decrease in pH over time was detected in both groups, with a significantly greater decline in pH in the KPS-1 group than in the NS group. There were no significant differences overall and over time in flow rate or vascular resistance between the KPS and NS groups. Conclusions: Perfusion with KPS-1 can successfully extend vascularized composite allograft perfusion cold storage for 24 h in a rat hindlimb model without significant edema or cell death.

14.
Polymers (Basel) ; 16(9)2024 Apr 25.
Article de Anglais | MEDLINE | ID: mdl-38732663

RÉSUMÉ

The research used polyethersulfone (PES) as a membrane material, polyvinylpyrrolidone (PVP) k30 and polyethylene glycol 400 (PEG 400) as water-soluble additives, and dimethylacetamide (DMAc) as a solvent to prepare hollow-fiber ultrafiltration membranes through a nonsolvent-induced phase separation (NIPS) process. The hydrophilic nature of PVP-k30 and PEG caused them to accumulate on the membrane surface during phase separation. The morphology, chemical composition, surface charge, and pore size of the PES membranes were evaluated by SEM, FTIR, zeta potential, and dextran filtration experiments. The paper also investigated how different spinning solution compositions affected membrane morphology and performance. The separation efficiency of membranes with four different morphologies was tested in single-protein and double-protein mixed solutions. The protein separation effectiveness of the membrane was studied through molecular weight cutoff, zeta potential, and static protein adsorption tests. In addition, the operating pressure and pH value were adjusted to improve ultrafiltration process conditions. The PES membrane with an intact sponge-like structure showed the highest separation factor of 11, making it a prime candidate membrane for the separation of bovine serum albumin (BSA) and lysozyme (LYS). The membrane had a minimal static protein adsorption capacity of 48 mg/cm2 and had excellent anti-fouling properties. When pH = 4, the BSA retention rate was 93% and the LYS retention rate was 23%. Furthermore, it exhibited excellent stability over a pH range of 1-13, confirming its suitability for protein separation applications.

15.
Front Bioeng Biotechnol ; 12: 1396892, 2024.
Article de Anglais | MEDLINE | ID: mdl-38720877

RÉSUMÉ

Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.

16.
Bioact Mater ; 38: 31-44, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38699238

RÉSUMÉ

Rapid development of checkpoint inhibitors has provided significant breakthroughs for cancer stem cell (CSC) therapy, while the therapeutic efficacy is restricted by hypoxia-mediated tumor immune evasion, especially hypoxia-induced CD47 overexpression in CSCs. Herein, we developed a genetically engineered CSC membrane-coated hollow manganese dioxide (hMnO2@gCMs) to elicit robust antitumor immunity by blocking CD47 and alleviating hypoxia to ultimately achieve the eradication of CSCs. The hMnO2 core effectively alleviated tumor hypoxia by inducing decomposition of tumor endogenous H2O2, thus suppressing the CSCs and reducing the expression of CD47. Cooperating with hypoxia relief-induced downregulation of CD47, the overexpressed SIRPα on gCM shell efficiently blocked the CD47-SIRPα "don't eat me" pathway, synergistically eliciting robust antitumor-mediated immune responses. In a B16F10-CSC bearing melanoma mouse model, the hMnO2@gCMs showed an enhanced therapeutic effect in eradicating CSCs and inhibiting tumor growth. Our work presents a simple, safe, and robust platform for CSC eradication and cancer immunotherapy.

17.
EClinicalMedicine ; 71: 102593, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38813444

RÉSUMÉ

Background: Postpartum blues (PPB) is a frequent syndrome of sad mood, crying spells, anxiety, restlessness, reduced appetite, and irritability, typically peaking day 5 postpartum. When severe, it greatly increases risk for later postpartum depression. This trial compared a dietary supplement to placebo on PPB severity. The supplement was designed to counter downstream effects of elevated monoamine oxidase A level, implicated in causing PPB. Methods: Participants recruited by advertisement from the Toronto region completed procedures at CAMH, Canada and/or participants' homes. Oral supplement or identical appearing relatively inert placebo were administered in randomised, double-blind fashion. Supplement was blueberry juice and extract given four times between nighttime day 3 and morning day 5 postpartum; tryptophan 2 g nighttime day 4 postpartum, and tyrosine 10 g morning day 5 postpartum. On day 5, depressed mood induction procedure (MIP) and postpartum blues were assessed. All data is presented (NCT03296956 closed, clinicaltrials.gov). Findings: Between January 2019 and December 2022, participants took supplement (n = 51) or placebo (n = 52). There was no significant effect on primary outcome MIP on visual analogue scale for depressed mood (mean difference = -0.39 mm, 95% CI: -6.42 to 5.65 mm). Stein Maternity Blues scores, exploratory PPB measure, was lower in the active group (effect size 0.62; median, interquartile range (IQR): active 2.00 (IQR 1, 4); placebo 4.00 (IQR 1.5, 6); regression with general linear model, supplement effect, ß coefficient = -1.50 (95%: CI -2.60, -0.40), p = 0.008; effect of CES-D crying category before supplement, p = 0.03-0.00000023). Twenty-six and 40 different adverse events occurred within 25% and 42% of supplement and placebo cases respectively (Chi-Square, p = 0.06). Interpretation: The primary outcome was negative for effect on depressed mood induction, however the supplement moderately reduced PPB. Funding: CAMH/Exeltis.

18.
J Am Chem Soc ; 146(19): 13499-13508, 2024 May 15.
Article de Anglais | MEDLINE | ID: mdl-38696816

RÉSUMÉ

Near-infrared (NIR) circularly polarized light absorbing or emitting holds great promise for highly sensitive and precise bioimaging, biosensing, and photodetectors. Aiming at designing NIR chiral molecular systems with amplified dissymmetry and robust chiroptical response, herein, we present a series of double π-helical dimers with longitudinally extended π-entwined substructures via Ullmann or Yamamoto homocoupling reactions. Circular dichroism (CD) spectra revealed an approximate linear bathochromic shift with the rising number of naphthalene subunits, indicating a red to NIR chiroptical response. Particularly, the terrylene diimide-entwined dimers exhibited the strongest CD intensities, with the maximal |Δε| reaching up to 393 M-1 cm-1 at 666 nm for th-TDI[2]; and a record-high chiroptical response (|ΔΔε|) between the neutral and dianionic species of 520 M-1 cm-1 at 833 nm for th-TDI[2]Cl was achieved upon further reduction to its dianionic state. Time-dependent density functional theory (TDDFT) calculations suggested that the pronounced intensification of the CD spectra originated from a simultaneous enhancement of both electric (µ) and magnetic (m) transition dipole moments, ultimately leading to an overall increase in the rotatory strength (R). Notably, the circularly polarized luminescence (CPL) brightness (BCPL) reached 77 M-1 cm-1 for th-TDI[2]Cl, among the highest values reported for NIR-CPL emitters. Furthermore, all chiral dianions exhibited excellent air stability under ambient conditions with half-life times of up to 10 days in N-methylpyrrolidone (NMP), which is significant for future biological applications and chiroptic switches.

19.
Transl Oncol ; 45: 101982, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38718436

RÉSUMÉ

Immune checkpoints inhibitors are effective but it needs more precise biomarkers for patient selection. We explored the biological significance of LINC00862 in pan-cancer by bioinformatics. And we studied its regulatory mechanisms using chromatin immunoprecipitation and RNA immunoprecipitation assays etc. TCGA and single-cell sequencing data analysis indicated that LINC00862 was overexpressed in the majority of tumor and stromal cells, which was related with poor prognosis. LINC00862 expression was related with immune cell infiltration and immune checkpoints expression, and had a high predictive value for immunotherapy efficacy. Mechanistically, LINC00862 competitively bound to miR-29c-3p to unleash SIRT1's tumor-promoting function. SIRT1 inhibitor-EX527 were screened by virtual screening and verified by in vitro and vivo assays. Notably, acetyltransferase P300-mediated super-enhancer activity stimulated LINC00862 transcription. Collectively, LINC00862 could be a diagnostic and prognostic biomarker. LINC00862 could also be a predictive biomarker for immunotherapy efficacy. Super-enhancer activity is the driver for LINC00862 overexpression in cervical cancer and gastric cancer.

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