RÉSUMÉ
The progression of lung adenocarcinoma (LUAD) from atypical adenomatous hyperplasia (AAH) to invasive adenocarcinoma (IAC) involves a complex evolution of tumour cell clusters, the mechanisms of which remain largely unknown. By integrating single-cell datasets and using inferCNV, we identified and analysed tumour cell clusters to explore their heterogeneity and changes in abundance throughout LUAD progression. We applied gene set variation analysis (GSVA), pseudotime analysis, scMetabolism, and Cytotrace scores to study biological functions, metabolic profiles and stemness traits. A predictive model for prognosis, based on key cluster marker genes, was developed using CoxBoost and plsRcox (CPM), and validated across multiple cohorts for its prognostic prediction capabilities, tumour microenvironment characterization, mutation landscape and immunotherapy response. We identified nine distinct tumour cell clusters, with Cluster 6 indicating an early developmental stage, high stemness and proliferative potential. The abundance of Clusters 0 and 6 increased from AAH to IAC, correlating with prognosis. The CPM model effectively distinguished prognosis in immunotherapy cohorts and predicted genomic alterations, chemotherapy drug sensitivity, and immunotherapy responsiveness. Key gene S100A16 in the CPM model was validated as an oncogene, enhancing LUAD cell proliferation, invasion and migration. The CPM model emerges as a novel biomarker for predicting prognosis and immunotherapy response in LUAD patients, with S100A16 identified as a potential therapeutic target.
Sujet(s)
Adénocarcinome pulmonaire , Marqueurs biologiques tumoraux , Évolution de la maladie , Tumeurs du poumon , Apprentissage machine , Analyse sur cellule unique , Microenvironnement tumoral , Humains , Adénocarcinome pulmonaire/génétique , Adénocarcinome pulmonaire/anatomopathologie , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Pronostic , Analyse sur cellule unique/méthodes , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Microenvironnement tumoral/génétique , Régulation de l'expression des gènes tumoraux , Immunothérapie/méthodes , Analyse de profil d'expression de gènesRÉSUMÉ
Succinate has been shown to be a potentially beneficial nutritional supplement with a diverse range of physiological functions. However, it remains unknown whether succinate supplementation regulates lipid metabolism in chickens. The aim of this study was to explore how succinate affects fat deposition and the underlying mechanism involved in broilers and to determine the most appropriate level of succinate supplementation in the diet. A total of 640 one-day-old male yellow-feathered broilers were randomly divided into 4 groups with 8 replicates and 20 broilers per replicate. A basal diet was provided to the control group (CON). The experimental broilers were fed diets containing 0.2% (L), 0.4% (M), or 0.6% (H) succinate and the study was lasted for 21 d. The linear (l) and quadratic (q) effects of succinate addition were determined. The results indicated that supplementation with 0.4% succinate reduced ADFI, serum triglycerides (l, q; P < 0.05), glucose (q; P < 0.05), and increased high-density lipidprotein cholesterol (l, q; P < 0.05) concentrations in broilers. Moreover, 0.4% succinate affects lipid metabolism by decreasing the abdominal fat percentage and adipocyte surface area, the expression of genes that promote liposynthesis in the abdominal fat and liver, as well as increasing the expression of genes that promote lipolysis in the abdominal fat and liver. In addition, increased cecal propionic acid content (q, P < 0.05) was found in the M group compared to the CON group. The 16S rRNA sequence analysis showed that group M altered cecum microbial composition by increasing the abundance of genera such as Blautia and Sellimonas (P < 0.05). LC-MS metabolomic analysis revealed that the differential metabolites between the M and CON groups were enriched in amino acid-related pathways. In conclusion, the optimum level of succinate added to broiler diets in the present study was 0.4%. Succinate can potentially reduce fat accumulation in broilers by modulating the composition of the gut flora and amino acid metabolism related to lipid metabolism.
Sujet(s)
Aliment pour animaux , Poulets , Régime alimentaire , Compléments alimentaires , Microbiome gastro-intestinal , Métabolisme lipidique , Acide succinique , Animaux , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Métabolisme lipidique/effets des médicaments et des substances chimiques , Mâle , Aliment pour animaux/analyse , Régime alimentaire/médecine vétérinaire , Compléments alimentaires/analyse , Acide succinique/métabolisme , Acide succinique/administration et posologie , Répartition aléatoire , Relation dose-effet des médicamentsRÉSUMÉ
Achieving satisfactory multi-carbon (C2+) products selectivity and current density under acidic condition is a key issue for practical application of electrochemical CO2 reduction reaction (CO2RR), but is challenging. Herein, we demonstrate that combining microenvironment modulation by porous channel structure and intrinsic catalytic activity enhancement via doping effect could promote efficient CO2RR toward C2+ products in acidic electrolyte (pH ≤ 1). The La-doped Cu hollow sphere with channels exhibits a C2+ products Faradaic efficiency (FE) of 86.2% with a partial current density of -775.8 mA cm-2. CO2 single-pass conversion efficiency for C2+ products can reach 52.8% at -900 mA cm-2. Moreover, the catalyst still maintains a high C2+ FE of 81.3% at -1 A cm-2. The channel structure plays a crucial role in accumulating K+ and OH- species near the catalyst surface and within the channels, which effectively suppresses the undesired hydrogen evolution and promotes C-C coupling. Additionally, the La doping enhances the generation of *CO intermediate, and also facilitates C2+ products formation.
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The functional properties of organic semiconductors are defined by the interplay between optically bright and dark states. Organic devices require rapid conversion between these bright and dark manifolds for maximum efficiency, and one way to achieve this is through multiexciton generation (S1â1TT). The dark state 1TT is typically generated from bright S1 after optical excitation; however, the mechanistic details are hotly debated. Here we report a 1TT generation pathway in which it can be coherently photoexcited, without any involvement of bright S1. Using <10-fs transient absorption spectroscopy and pumping sub-resonantly, 1TT is directly generated from the ground state. Applying this method to a range of pentacene dimers and thin films of various aggregation types, we determine the critical material properties that enable this forbidden pathway. Through a strikingly simple technique, this result opens the door for new mechanistic insights into 1TT and other dark states in organic materials.
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Hydroxylamine (HA, NH2OH) is a critical feedstock in the production of various chemicals and materials, and its efficient and sustainable synthesis is of great importance. Electroreduction of nitrate on Cu-based catalysts has emerged as a promising approach for green ammonia (NH3) production, but the electrosynthesis of HA remains challenging due to overreduction of HA to NH3. Herein, we report the first work on ketone-mediated HA synthesis using nitrate in water. A metal-organic-framework-derived Cu catalyst was developed to catalyze the reaction. Cyclopentanone (CP) was used to capture HA in situ to form CP oxime (CP-O) with CâN bonds, which is prone to hydrolysis. HA could be released easily after electrolysis, and CP was regenerated. It was demonstrated that CP-O could be formed with an excellent Faradaic efficiency of 47.8%, a corresponding formation rate of 34.9 mg h-1 cm-2, and a remarkable carbon selectivity of >99.9%. The hydrolysis of CP-O to release HA and CP regeneration was also optimized, resulting in 96.1 mmol L-1 of HA stabilized in the solution, which was significantly higher than direct nitrate reduction. Detailed in situ characterizations, control experiments, and theoretical calculations revealed the catalyst surface reconstruction and reaction mechanism, which showed that the coexistence of Cu0 and Cu+ facilitated the protonation and reduction of *NO2 and *NH2OH desorption, leading to the enhancement for HA production.
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A novel polyethyleneimine/polydopamine-functionalized ß-cyclodextrin supported fly ash adsorbent (PEI/PDA/ß-CD/FA) had been synthesized to uptake uranium from polluted water. At pH = 5.0 and T = 298 K, the uranium uptake efficiency and capacity of PEI/PDA/ß-CD/FA reached to 98.7 % and 622.8 mg/g, respectively, which were much higher than those of FA (71.4 % and 206.7 mg/g).The excellent uranium uptake properties of PEI/PDA/ß-CD/FA could be explained by three points: (1) using ß-CD as a supporting material could effectively avoid the aggregation of FA and improve the hydrophily of FA; (2) the unique cavity structure of ß-CD could form chelates with uranyl ions; (3) the formation of PEI/PDA co-deposition coating on FA further enhanced the affinity of FA to UO22+. With the presence of interfering ions, the uptake efficiency of PEI/PDA/ß-CD/FA for uranium was still up to 94.5 % after five cycles, indicating the high selectively and recoverability of PEI/PDA/ß-CD/FA. In terms of the results of characterizations, uranium was captured by PEI/PDA/ß-CD/FA via electrostatic attraction, hydrogen bond, coordination and complexation. To sum up, PEI/PDA/ß-CD/FA was expected to be used for actual sewage treatment owing to its excellent uranium uptake efficiency/capacity, selectivity, cycle stability and feasibility of actual application.
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Calf intestines are colonized by rich and complex microbial communities, playing a crucial role in animal physiology, metabolism, nutrition, and immune function. In this study, we provide insight into the composition of fecal microbial bacteria and fungi, respectively, as well as the cross-kingdom interactions. We investigated the intestinal microbiota of different breeds of calves by characterizing the bacterial and fungal communities in the rectal feces of Holstein calves and German Simmental × Holstein cross F1 generation (GXH) using 16S rRNA and ITS amplicon sequencing techniques. PICRUSt2 (version 2.2.0) were used to determine microbial diversity and function and explore the reasons why Holstein calves are more susceptible to diarrhea. The results revealed no significant difference in the diversity of fecal microbiota among the groups (p > 0.05). We identified Firmicutes, Bacteroidetes, and Proteobacteria as the dominant bacterial phyla in the fecal bacterial communities of the two breeds of calves. Ascomycota and Basidiomycota play important roles in the fungal community but differ in relative abundance. Bacteroides was the dominant genus at the group level for calf fecal microbiota in both breeds. The relative abundance of Prevotella, Escherichia-Shigella, Peptostreptococcus, and Butyricicoccus was higher in Holstein calves, and the relative abundance of Faecalibacterium, Megamonas, Butyricicoccus, and Alloprevotella was lower than GXH group. Aspergillus and Cladosporium were the dominating genera of fecal fungi in both groups of calves. LEfSe analysis revealed 33 different bacteria and 23 different fungi between the two groups, with more differential strains found in GXH. In addition, the feces fungi-bacteria interkingdom interactions varied among breeds. Thus, the composition and structure of bacterial and fungal communities in calf feces varied by breed, indicating a potential association between breed and microbial communities. We also found differences in the network between bacterial-fungal kingdoms. We explain the reasons for Holstein calves being more prone to diarrhea. This indicated that breed makes differences in calf diarrhea rates by influencing gut microbial composition and interactions.
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Magneto-optical effects (MOE), interfacing the fundamental interplay between magnetism and light, have served as a powerful probe for magnetic order, band topology, and valley index. Here, based on multiferroic and topological bilayer antiferromagnets (AFMs), we propose a layer control of MOE (L-MOE), which is created and annihilated by layer-stacking or an electric field effect. The key character of L-MOE is the sign-reversible response controlled by ferroelectric polarization, the Néel vector, or the electric field direction. Moreover, the sign-reversible L-MOE can be quantized in topologically insulating AFMs. We reveal that the switchable L-MOE originates from the combined contributions of spin-conserving and spin-flip interband transitions in spin-valley splitting AFMs, a phenomenon not observed in conventional AFMs. Our findings bridge the ancient MOE to the emergent realms of layertronics, valleytronics, and multiferroics and may hold immense potential in these fields.
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Objective: To further explore the effect of vaccination regimen and frequency on clinical outcomes of breakthrough infections caused by the Omicron variant, as well as the durability of vaccine effectiveness. Methods: A retrospective, propensity score matching, real-world cohort study was conducted. Vaccination frequency was categorized into regular vaccination, first booster, and second booster. Results: A total of 7428 cases were included, with 3910 (53 %) being male. The median age was 39 years. BA.2 than BA.5/5.2 infection presented with more pulmonary symptoms and fewer influenza-like symptoms. Among the 3516 cases of BA.5/5.2 breakthrough infections, patients who received the second booster than the first booster or regular vaccination had higher first IgM and IgG titers and first cycle thredhold values for N gene on admission, a lower percentage of fever, lower peak body temperatures, and a higher percentage of asymptomatic cases. Patients who received the first booster vaccinated with homologous mRNA or heterologous inactivated plus mRNA vaccines than homologous inactivated vaccines had higher first IgM and IgG titers, a higher percentage of asymptomatic cases, and a lower percentage of fever. Moreover, significantly different first IgG titers were observed among patients receiving the second booster vaccinated with any of the three regimens. There was no statistical difference between booster regimens of homologous mRNA vaccines and heterologous inactivated plus mRNA vaccines. Patients in Month 7- than Month 0-6 after the first booster had lower first IgM and IgG titers and first cycle thredhold values, a lower percentage of asymptomatic cases, and a higher percentage of fever; and a higher percentage of pneumonia after the second booster. Conclusions: Repeated booster vaccinations every six months, with priority given to heterologous mRNA vaccine booster regimens in countries previously primarily using inactivated vaccines, may provide protection for adult patients with Omicron-variant breakthrough infections and improve clinical outcomes.
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Mechanically strong and damage-tolerant corrosion protection layers are of great technological importance. However, corrosion protection layers with high modulus (>1.5 GPa) and tensile strength (>100 MPa) are rare. Here, we report that a 130 µm thick densified wood veneer with a Young's modulus of 34.49 GPa and tensile strength of 693 MPa exhibits both low diffusivity for metal ions and the ability of self-recovery from mechanical damage. Densified wood veneer is employed as an intermediate layer to render a mechanically strong corrosion protection structure, referred to as "wood corrosion protection structure", or WCPS. The corrosion rate of low-carbon steel protected by WCPS is reduced by 2 orders of magnitude than state-of-the-art corrosion protection layers during a salt spray test. The introduction of engineered wood veneer as a thin and mechanically strong material points to new directions of sustainable corrosion protection design.
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Direct fixation of N2 to N-containing value-added chemicals is a promising pathway for sustainable chemical manufacturing. There is extensive demand for cyclohexanone oxime because it is the essential feedstock of Nylon 6. Currently, cyclohexanone oxime is synthesized under harsh conditions that consume a considerable amount of energy. Herein, we report a novel approach to synthesize cyclohexanone oxime by in situ NO3- generation from air under ambient conditions. This process was carried out through an integrated strategy including plasma-assisted air-to-NOx and co-electrolysis of NOx and cyclohexanone. A high rate of cyclohexanone oxime formation at 20.1 mg h-1 cm-2 and a corresponding faradaic efficiency (FE) of 51.4% was achieved over a Cu/TiO2 catalyst, and the selectivity of cyclohexanone oxime was >99.9% on the basis of cyclohexanone. The C-N bond formation mechanism was examined by in situ experiments and theoretical calculations, which showed that cyclohexanone oxime forms through the reaction between an NH2OH intermediate and cyclohexanone.
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In this work, the adsorption and sensing behavior of Ag-doped MoSe2/ZnO heterojunctions for H2, CH4, CO2, NO, CO, and C2H4 have been studied based on density functional theory (DFT). In gas adsorption analysis, the adsorption energy, adsorption distance, transfer charge, total electron density, density of states (DOS), energy band structure, frontier molecular orbital, and work function (WF) of each gas has been calculated. Furthermore, the reusability and stability of the Ag-doped MoSe2/ZnO heterojunctions have also been studied. The results showed that Ag-doped MoSe2/ZnO heterojunctions have great potential to be a candidate of highly selective and responsive gas sensors for NO detection with excellent reusability and stability.
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Efficient and sustainable amino acid synthesis is essential for industrial applications. Electrocatalytic reductive amination has emerged as a promising method, but challenges such as undesired side reactions and low efficiency persist. Herein, we demonstrated a lignin-derived catalyst for alanine synthesis. Carbon nanosheets (CNSs) were synthesized from lignin via a template-assisted method and doped with nitrogen and sulfur to boost reductive amination and suppress side reactions. The resulting N,S-co-doped carbon nanosheets (NS-CNSs) exhibited outstanding electrochemical performance. It achieved a maximum alanine Faradaic efficiency of 79.5%, and a yield exceeding 1,199 µmol h-1 cm-2 on NS-CNS, with a selectivity above 99.9%. NS-CNS showed excellent durability during long-term electrolysis. Kinetic studies including control experiments and theoretical calculations provided further insights into the reaction pathway. Moreover, NS-CNS catalysts demonstrated potential in upgrading real-world polylactic acid plastic waste, yielding value-added alanine with a selectivity over 75%.
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Cu-based electrocatalysts have great potential for facilitating CO2 reduction to produce energy-intensive fuels and chemicals. However, it remains challenging to obtain high product selectivity due to the inevitable strong competition among various pathways. Here, we propose a strategy to regulate the adsorption of oxygen-associated active species on Cu by introducing an oxophilic metal, which can effectively improve the selectivity of C2+ alcohols. Theoretical calculations manifested that doping of Lewis acid metal Al into Cu can affect the C-O bond and Cu-C bond breaking toward the selectively determining intermediate (shared by ethanol and ethylene), thus prioritizing the ethanol pathway. Experimentally, the Al-doped Cu catalyst exhibited an outstanding C2+ Faradaic efficiency (FE) of 84.5% with remarkable stability. In particular, the C2+ alcohol FE could reach 55.2% with a partial current density of 354.2 mA cm-2 and a formation rate of 1066.8 µmol cm-2 h-1. A detailed experimental study revealed that Al doping improved the adsorption strength of active oxygen species on the Cu surface and stabilized the key intermediate *OC2H5, leading to high selectivity toward ethanol. Further investigation showed that this strategy could also be extended to other Lewis acid metals.
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Near-infrared (NIR) photothermal manipulation has emerged as a promising and noninvasive technology for neuroscience research and disease therapy for its deep tissue penetration. NIR stimulated techniques have been used to modulate neural activity. However, due to the lack of suitable in vivo control systems, most studies are limited to the cellular level. Here, a NIR photothermal technique is developed to modulate cellular excitability and animal behaviors in Caenorhabditis elegans in vivo via the thermosensitive transient receptor potential vanilloid 1 (TRPV1) channel with an FDA-approved photothermal agent indocyanine green (ICG). Upon NIR stimuli, exogenous expression of TRPV1 in AFD sensory neurons causes Ca2+ influx, leading to increased neural excitability and reversal behaviors, in the presence of ICG. The GABAergic D-class motor neurons can also be activated by NIR irradiation, resulting in slower thrashing behaviors. Moreover, the photothermal manipulation is successfully applied in different types of muscle cells (striated muscles and nonstriated muscles), enhancing muscular excitability, causing muscle contractions and behavior changes in vivo. Altogether, this study demonstrates a noninvasive method to precisely regulate the excitability of different types of cells and related behaviors in vivo by NIR photothermal manipulation, which may be applied in mammals and clinical therapy.
Sujet(s)
Antinéoplasiques , Caenorhabditis elegans , Animaux , Vert indocyanine , Lignée cellulaire tumorale , Comportement animal , MammifèresRÉSUMÉ
The renewable-energy-powered electroreduction of nitrate (NO3 - ) to ammonia (NH3 ) has garnered significant interest as an eco-friendly and promising substitute for the Haber-Bosch process. However, the sluggish kinetics hinders its application at a large scale. Herein, we first calculated the N-containing species (*NO3 and *NO2 ) binding energy and the free energy of the hydrogen evolution reaction over Cu with different metal dopants, and it was shown that Zn was a promising candidate. Based on the theoretical study, we designed and synthesized Zn-doped Cu nanosheets, and the as-prepared catalysts demonstrated excellent performance in NO3 - -to-NH3 . The maximum Faradaic efficiency (FE) of NH3 could reach 98.4 % with an outstanding yield rate of 5.8â mol g-1 h-1 , which is among the best results up to date. The catalyst also had excellent cycling stability. Meanwhile, it also presented a FE exceeding 90 % across a wide potential range and NO3 - concentration range. Detailed experimental and theoretical studies revealed that the Zn doping could modulate intermediates adsorption strength, enhance NO2 - conversion, change the *NO adsorption configuration to a bridge adsorption, and decrease the energy barrier, leading to the excellent catalytic performance for NO3 - -to-NH3 .
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Renewable-energy-driven CO2 electroreduction provides a promising way to address the growing greenhouse effect issue and produce value-added chemicals. As one of the bulk chemicals, formic acid/formate has the highest revenue per mole of electrons among various products. However, the scaling up of CO2-to-formate for practical applications with high faradaic efficiency (FE) and current density is constrained by the difficulty of precisely reconciling the competing intermediates (*COOH and HCOO*). Herein, a Zn-induced electron-rich Sn electrocatalyst was reported for CO2-to-formate with high efficiency. The faradaic efficiency of formate (FEformate) could reach 96.6%, and FEformate > 90% was maintained at formate partial current density up to 625.4 mA cm-1. Detailed study indicated that catalyst reconstruction occurred during electrolysis. With appropriate electron accumulation, the electron-rich Sn catalyst could facilitate the adsorption and activation of CO2 molecules to form a intermediate and then promoted the carbon protonation of to yield a HCOO* intermediate. Afterwards, the HCOO* â HCOOH* proceeded via another proton-coupled electron transfer process, leading to high activity and selectivity for formate production.
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Electrocatalytic CO2 reduction is a typical reaction involving two reactants (CO2 and H2O). However, the role of H2O dissociation, which provides active *H species to multiple protonation steps, is usually overlooked. Herein, we construct a dual-active sites catalyst comprising atomic Cu sites and Cu nanoparticles supported on N-doped carbon matrix. Efficient electrosynthesis of multi-carbon products is achieved with Faradaic efficiency approaching 75.4% with a partial current density of 289.2 mA cm-2 at -0.6 V. Experimental and theoretical studies reveal that Cu nanoparticles facilitate the C-C coupling step through *CHO dimerization, while the atomic Cu sites boost H2O dissociation to form *H. The generated *H migrate to Cu nanoparticles and modulate the *H coverage on Cu NPs, and thus promote *CO-to-*CHO. The dual-active sites effect of Cu single-sites and Cu nanoparticles gives rise to the catalytic performance.
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Objectives: Rheumatoid arthritis (RA) is a disease characterised by bone destruction and systemic inflammation, and interleukin-6 (IL-6) is a therapeutic target for treating it. The study aimed at investigating the sources of IL-6 and the influence of hypoxia-inducible factor-1α (HIF-1α) on IL-6 production by B cells in RA patients. Methods: The phenotype of IL-6-producing cells in the peripheral blood of RA patients was analysed using flow cytometry. Bioinformatics, real-time polymerase chain reaction, Western blot and immunofluorescence staining were used to determine the IL-6 production and HIF-1α levels in B cells. A dual-luciferase reporter assay and chromatin immunoprecipitation were used to investigate the regulatory role of HIF-1α on IL-6 production in human and mouse B cells. Results: Our findings revealed that B cells are major sources of IL-6 in the peripheral blood of RA patients, with the proportion of IL-6-producing B cells significantly correlated with RA disease activity. The CD27-IgD+ naïve B cell subset was identified as the typical IL-6-producing subset in RA patients. Both HIF-1α and IL-6 were co-expressed by B cells in the peripheral blood and synovium of RA patients, and HIF-1α was found to directly bind to the IL6 promoter and enhance its transcription. Conclusion: This study highlights the role of B cells in producing IL-6 and the regulation of this production by HIF-1α in patients with RA. Targeting HIF-1α might provide a new therapeutic strategy for treating RA.