Synergistic engineering of heterostructure and oxygen vacancy in cobalt hydroxide/aluminum oxyhydroxide as bifunctional electrocatalysts for urea-assisted hydrogen production.

Designing inexpensive, high-efficiency and durable bifunctional catalysts for urea oxidation reaction (UOR) and hydrogen evolution reaction (HER) is an encouraging tactic to produce hydrogen with reduced energy expenditure. Herein, oxygen vacancy-rich cobalt hydroxide/aluminum oxyhydroxide heterostructure on nickel foam (denoted as Co(OH)2/AlOOH/NF-100) has been fabricated using one step hydrothermal process. Theoretical calculation and experimental results indicate the electrons transfer from Co(OH)2 to highly active AlOOH results in the interfacial charge redistribution and optimization of electronic structure. Abundant oxygen vacancies in the heterostructure could improve the conductivity and simultaneously serve as the active sites for catalytic reaction. Consequently, the optimal Co(OH)2/AlOOH/NF-100 demonstrates excellent electrocatalytic performance for HER (62.9 mV@10 mA cm-2) and UOR (1.36 V@10 mA cm-2) due to the synergy between heterointerface and oxygen vacancies. Additionally, the in situ electrochemical impedance spectrum (EIS) for UOR suggests that the heterostructured catalyst exhibits rapid reaction kinetics, mass transfer and current response. Importantly, the urea-assisted electrolysis composed of the Co(OH)2/AlOOH/NF-100 manifests a low cell voltage (1.48 V @ 10 mA cm-2) in 1 M KOH containing 0.5 M urea. This work presents a promising avenue to the development of HER/UOR bifunctional electrocatalysts.

Synergistic manipulation of sulfur vacancies and palladium doping of In2S3 for enhanced photocatalytic H2 production.

In this study, a simple one-pot synthesis process is employed to introduce Pd dopant and abundant S vacancies into In2S3 nanosheets. The optimized Pd-doped In2S3 photocatalyst, with abundant S vacancies, demonstrates a significant enhancement in photocatalytic hydrogen evolution. The joint modification of Pd doping and rich S vacancies on the band structure of In2S3 result in an improvement in both the light absorption capacity and proton reduction ability. It is worth noting that photogenerated electrons enriched by S vacancies can rapidly migrate to adjacent Pd atoms through an efficient transfer path constructed by Pd-S bond, effectively suppressing the charge recombination. Consequently, the dual-defective In2S3 shows an efficient photocatalytic H2 production rate of 58.4 ± 2.0 µmol·h-1. Additionally, further work has been conducted on other ternary metal sulfide, ZnIn2S4. Our findings provide a new insight into the development of highly efficient photocatalysts through synergistic defect engineering.

Noninvasive assessment of single kidney glomerular filtration rate using multiple diffusion weighted imaging models.

PURPOSE: This study aimed to assess single kidney glomerular filtration rate (GFR) using various diffusion weighted imaging (DWI) models. METHODS: We reviewed adult patients with kidney diseases who underwent magnetic resonance imaging (MRI) examination from February 2021 to December 2023. DWI with 13 b-values was performed using 3.0-T scanners. Diffusion parameters were calculated with multi-slice ROIs positioned in renal parenchyma using four DWI models, including monoexponential model (MEM), diffusion kurtosis imaging (DKI), stretched exponential model (SEM), and intravoxel incoherent motion (IVIM). The split GFRs were measured by 99mTc-DTPA scintigraphy using Gates' method. Four different regression algorithms including the linear regression, regression tree, Gaussian regression and support vector machine (SVM) regression were employed to predict the GFR value based on different diffusion parameters. The leave-one-out cross validation was used to evaluate prediction ability of different models, and the performance of each model was quantified using the root mean square error (RMSE) and correlation coefficient. RESULTS: Fifteen (male/female, 10/5; age, 41.60±10.83 years) patients were included in this study. Among the four DWI models, the IVIM parameters with SVM regression model achieved the best performance with 0.184 RMSE and 0.789 correlation coefficient ( p < 0.001 ). The parameters combining the four DWI models with SVM regression algorithm achieved the best performance in this study, with 0.171 RMSE and 0.815 correlation coefficient ( p < 0.001 ). CONCLUSION: The DWI characteristics are able to serve as imaging biomarkers for assessing the function of single kidney. The integration of DWI into clinical practice could contribute to the advancement of non-invasive diagnostic methodologies.

Ring-extended carbazole modification to activate efficient phosphorescent OLED performance of traditional host materials.

A novel "Ring-expansion" strategy is proposed to optimize traditional host molecular structures, featuring a rigid molecular skeleton and excellent transport of carriers. Consequently, the two novel host materials facilitate the fabrication of efficient phosphorescent OLEDs with suppressed efficiency roll-off compared to OLEDs based on the conventional host material (mCP).

Ozone disinfection of waterborne pathogens: A review of mechanisms, applications, and challenges.

Water serves as a critical vector for the transmission of pathogenic microorganisms, playing a pivotal role in the emergence and propagation of numerous diseases. Ozone (O3) disinfection technology offers promising potential for mitigating the spread of these pathogens in aquatic environments. However, previous studies have only focused on the inactivated effect of O3 on a single pathogenic microorganism, lacking a comprehensive comparative analysis of various influencing factors and different types of pathogens, while the cost-effectiveness of O3 technology has not been mentioned. This review synthesized the migration characteristics of various pathogenic microorganisms in water bodies and examined the properties, mechanisms, and influencing factors of O3 inactivation. It evaluated the efficacy of O3 against diverse pathogens, namely bacteria, viruses, protozoa, and fungi, and provided a comparative analysis of their sensitivities to O3. The formation and impact of harmful disinfection by-products (DBPs) during the O3 inactivation process were assessed, alongside an analysis of the cost-effectiveness of this method. Additionally, potential synergistic treatment processes involving O3 were proposed. Based on these findings, recommendations were made for optimizing the utilization of O3 in water inactivation in order to formulate better inactivation strategies in the post-pandemic eras.

Stiffness-induced modulation of ERG transcription factor in chronic liver disease.

Chronic liver disease (CLD) is characterised by liver sinusoidal endothelial cells (LSECs) dysfunction. Mechanical forces and inflammation are among the leading factors. ETS-related gene (ERG) is an endothelial-specific transcription factor, involved in maintaining cell quiescence and homeostasis. Our study aimed to understand the expression and modulation of ERG in CLD. ERG expression was characterised and correlated to clinical data in human liver cirrhosis at different disease stages. ERG dynamics in response to stiffness and inflammation were investigated in primary healthy and cirrhotic rat LSEC and in human umbilical vein endothelial cells (HUVECs). ERG is markedly downregulated in cirrhosis independently of disease stage or aetiology and its expression is modulated by substrate stiffness in ECs. Inflammation downregulates ERG in cells on physiological stiffness, but not on high stiffness, suggesting a complementary role of inflammation and stiffness in suppressing ERG. This study outlines ERG as an LSEC inflammation and stiffness-responsive transcription factor in cirrhosis.

Options for environmental regulation policy under China's carbon peaking target: Energy supply policy or carbon tax policy?

China plans to achieve the carbon peaking target by 2030 and will maybe implement a series of environmental regulation policies, primarily including energy supply policy (such as coal consumption constraint and non-fossil energy development) and carbon tax policy. This paper simulates these policies using a computable general equilibrium model. The simulation results indicate that carbon tax policy has a finite impact on the economy, the emissions reduction effect is also limited and carbon tax policy alone is insufficient to achieve China's 2030 carbon peaking target. The coal consumption constraint policy has a good emissions reduction effect, but is not conducive to economic growth. The non-fossil energy development policy can increase energy supply and promote economic growth, but the emissions reduction effect is inadequate. In general, the simultaneous implementation of the coal consumption constraint and non-fossil energy development policies could not only achieve the carbon peaking goal, but also narrow the energy gap and reduce pressure on economic growth. However, it is notable that if carbon tax policy and energy supply policy are implemented simultaneously, the emissions reduction effect of carbon tax policy would be significantly reduced; therefore, it is likely that no carbon tax will be levied in China.

Domain Dynamics Response to Polarization Switching in Relaxor Ferroelectrics.

Nanoscale polar regions, or nanodomains (NDs), are crucial for understanding the domain structure and high susceptibility of relaxors. However, unveiling the evolution and function of NDs during polarization switching at the microscopic level is of great challenge. The experimental in situ characterization of NDs under electric-field perturbations, and computational accurate prediction of the dipole switching within a sufficiently large supercell, are notoriously tricky and tedious. These difficulties hinder a full understanding of the link between micro domain dynamics and macro polarization switching. Herein, the real-time evolution of NDs at the nanoscale is observed and visualized during polarization switching in an exemplary relaxor system of Bi5- xLaxMg0.5Ti3.5O15. Two fundamentally different domain switching pathways and dynamic characteristics are revealed: one steep, bipolar-like switching between two degenerate polarization states; and another flat, multi-step switching process with a thermodynamically stable non-polar mesophase mediating the degenerate polarization states. The two are determined by the distinct Landau energy landscapes that are strongly dependent on the intrinsic domain configurations and interdomain interactions. This work bridges the gap between micro domain dynamics and macro polarization switching, providing a guiding principle for the strategic design and optimization of relaxors.

Potential immunologic and prognostic roles of CHRNA6 in SCLC and pan-cancer.

Background: Small cell lung cancer (SCLC) is considered the most malignant subtype of lung cancer, and it has a restricted range of therapeutic choices. The emergence of immunotherapy has offered new possibilities for patients with SCLC. However, the scarcity of clinical specimens has hampered the progress of clinical studies and we still face a shortage of dependable indicators to forecast the effectiveness of immunotherapy for SCLC. Methods: In our study, we assessed the ImmuneScore and StromalScore of 81 SCLC samples obtained from the cBioPortal database. By comparing gene expression differences between the high and low immune scores groups, we identified 24 differentially expressed genes. Subsequently, an intersection was performed with genes that exhibited differential expression between normal and SCLC tissues, leading us to isolate the gene CHRNA6. To gain a deeper insight into the possible significance of CHRNA6 in SCLC, we singled out 50 genes that showed the most pronounced positive and negative associations with its expression. We then pinpointed hub genes for subsequent functional enrichment analyses by establishing a protein-protein interactions network. We additionally assessed the link between CHRNA6 expression in SCLC and characteristics of the immune microenvironment, along with the efficacy of immunotherapy, using the CIBERSORT, immunophenoscores (IPS), and tumor immune dysfunction and exclusion (TIDE) algorithms. Furthermore, we confirmed the prognostic impact of CHRNA6 expression in SCLC patients undergoing immunotherapy within a clinical cohort. Lastly, we obtained data from The Cancer Genome Atlas (TCGA) to investigate CHRNA6 expression in various tumors and its associations with genetic alterations, DNA methylation, copy number variation, clinicopathological characteristics, biological processes, immune microenvironment, prognosis, and drug sensitivity. Results: In SCLC, we found that CHRNA6 function was associated with immune activation pathways such as antigen presentation processing and positive regulation of adaptive immune response, and that CHRNA6 demonstrated a strong correlation with immune cells infiltration. In addition, analysis of the clinical cohort revealed that patients with SCLC who exhibited elevated expression of CHRNA6 experienced better responses to immunotherapy. Our pan-cancer analysis disclosed that the expression of CHRNA6 is dysregulated in a multitude of cancers, potentially due to genetic mutations, copy number gains, and DNA demethylation. The gene set enrichment analysis (GSEA) outcomes indicated that CHRNA6 participates in immune responses and may play a positive immune regulatory role in most cancers. Furthermore, CHRNA6 has been observed to have a notable relationship with immune checkpoints, immunomodulators, immune cell infiltration, patient outcomes, and drug sensitivity across various cancers. Conclusions: Our findings indicate that the CHRNA6 may act as a predictive indicator for SCLC patients receiving immunotherapy. The study also uncovers the aberrant expression of CHRNA6 in a range of human cancers and its potential roles in immunology and prognosis, offering novel perspectives for tailored cancer therapies.

Single-atom oxide-decorated AuNPs for universal enhancement in SERS detection of pesticide residues.

BACKGROUND: In the context of modern agriculture, the proliferation of chemical use calls for enhanced pesticide detection to safeguard food quality and public health. The development of accurate testing methodologies is imperative to mitigate the environmental impact of pesticides and ensure the integrity of ecosystems, thereby reflecting the pressing need for advancements in agricultural safety protocols. Therefore, the development of highly sensitive monitoring technology for detecting pesticide residues in agricultural products is necessary for safeguarding human health, ensuring food safety, and maintaining environmental sustainability. RESULTS: Herein, a controllable surface charge on single tungsten atom-modified gold nanoparticles was used to create an electrostatic force with positively charged pesticide residues. Moreover, hydrogen bonds formed by single-atom sites can induce analyte-adsorbed nanoparticle aggregation, and the sizes of single-tungsten-atom-decorated AuNPs can maintain a gap between each other, resulting in improved SERS detection sensitivity through analyte enrichment at gold nanoparticle hotspots. In terms of the detection limits for pesticide residue analysis, we can effectively achieve an ultrahigh sensitivity of 0.1 ppb for acetamiprid, paraquat and carbendazim, which is among the best SERS sensitivities at the state of the art. For apple sample analysis, our work demonstrated good reproductivity (RSD<6 %) and a strong linear relationship (R2 ≥ 0.97) for 4 pesticide residues after optimizing the pretreatment process, which proves the enormous potential in quantitative analysis. SIGNIFICANCE: Single-atom sites hotspot are firstly successfully achieved and uniformly dispersed between Au nanoparticle, which can effectively increase the sensitivity, keep stability of the Raman scattering signals and possess a significant improvement beyond that of undecorated hotspots when applied in pesticide residue detection. This method can be employed as a universal strategy to capture pesticide residues at hotspots for SERS detection.

Circulating Capsid-Antibody-Complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B.

Chronic infection with Hepatitis B Virus (HBV) often results in a dysfunctional virus-specific T cell response hampering viral clearance. Paradoxically, intrahepatic inflammatory responses that contribute more to liver histopathology than to viral suppression are commonly observed, which are widely believed to be cell mediated. The involvement of humoral immunity in this process however is not well documented. To investigate the possible roles of HBV Capsid-Antibody Complexes (CACs) in eliciting chronic liver inflammation, we developed a novel microplate-based assay for the quantification of CACs in serum. The CACs assay showed high sensitivity and specificity with its readout closely correlating with the molecular features of CACs. A cross-sectional study on untreated chronic hepatitis B (CHB) patients showed a 77% positive rate for CACs with significant association with alanine transaminase (ALT), intrahepatic inflammation, and complement deposition, suggestive of its functional role in hepatic injury. Multiple staining of complement activation fragment C4d with major leukocyte and myofibroblast markers revealed an intertwined picture in periportal area with a morphology reminiscent of "piecemeal necrosis". In a pooled cohort with ALT levels lower than 40 IU/ml, CACs alone revealed subclinical liver inflammation. We provide definitive evidence for a causative role for CACs in complement-mediated intrahepatic immunopathology, an additional mechanism contributing to liver damage in CHB. Assessment of CACs in serum complements current clinical markers for assessing CHB associated inflammation.

Continuous self-circulating up-flow granular sludge fluidized bed process treating low-strength real municipal wastewater at high hydraulic loads.

Conditions conducive to aerobic granular sludge (AGS) growth and maintenance are very difficult to realize in continuous-flow biological treatment processes. This study conducted a continuous-flow self-circulating up-flow granular sludge fluidized bed (Zier process) treating real urban wastewater approximately one year. The substantial self-circulating multiple times (RSCMT, 8-15 times) and up-flow velocity (8-15 m/h) generated by aeration, the only power equipment in Zier process, facilitated pollutant removal, particle granulation and stabilization. With hydraulic retention time of 5 h, RSCMT of 9.3-14.4 times and chemical oxygen demand (COD)/total nitrogen (TN) ratio of 5.9 ±â€¯1.0, the effluent COD, ammonia nitrogen and TN were 28.6 ±â€¯7.7, 1.1 ±â€¯1.2, and 13.3 ±â€¯1.7 mg/L, respectively. The median particle size was 150-250 µm and effluent suspended solids concentration was 33.4 ±â€¯14.5 mg/L. It is unnecessary to set up sludge reflux which simplifies the subsequent mud-water separation facilities. The Zier process provides a new process structure for implementation of continuous-flow AGS process.

CRISPR/Cas9-mediated knockout of the abdominal-B homeotic gene in the global pest, fall armyworm (Spodoptera frugiperda).

The Homeotic complex (Hox) genes play a crucial role in determining segment identity and appendage morphology in bilaterian animals along the antero-posterior axis. Recent studies have expanded to agricultural pests such as fall armyworm (FAW), scientifically known as Spodoptera frugiperda J. E. Smith (Lepidoptera: Noctuidae), which significantly threatens global agricultural productivity. However, the specific role of the hox gene Sfabd-B in FAW remains unexplored. This research investigates the spatial and temporal expression patterns of Sfabd-B in various tissues at different developmental stages using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, we explored the potential function of the Sfabd-B gene located in the FAW genome using CRISPR/Cas9 technology. The larval mutant phenotypes can be classified into three subgroups as compared with wild-type individuals, that is, an excess of pedis in the posterior abdomen, deficient pedis due to segmental fusion and deviations in the posterior abdominal segments. Importantly, significant differences in mutant phenotypes between male and female individuals were also evident during the pupal and adult phases. Notably, both the decapentaplegic (dpp) and cuticular protein 12 (cp 12) genes displayed a substantial marked decrease in expression levels in the copulatory organ of male mutants and the ovipositor of female mutants compared with the wild type. These findings highlight the importance of Sfabd-B in genital tract patterning, providing a potential target for improving genetic control.

Soluble trehalase responds to heavy metal stimulation by regulating apoptosis in Neocaridina denticulata sinensis.

Trehalase plays an important role in insect metabolism and development by hydrolyzing blood sugar trehalose, but it seems to perform primarily an immunomodulatory function in crustaceans whose blood sugar is glucose. Metal ions as pollutants seriously affecting crustacean health, but studies on trehalase in metal immunity are still limited. In this study, a soluble trehalase (NdTre1) that could bind to multiple metals was identified from Neocaridina denticulata sinensis for investigating metal resistance. Expression profiling revealed that NdTre1 was mainly expressed in the gill and was significantly decreased following stimulation with copper (Cu²âº) and cadmium (Cd²âº). Transcriptomic analysis of gills revealed an increase in ecdysone synthesis after interference with NdTre1. Increased ecdysone activated the endogenous mitochondrial pathway and the mitogen activated protein kinase (MAPK) pathway to further induced apoptosis. In vitro, Escherichia coli overexpressing recombinant NdTre1 had higher survival and faster growth rates to better adapted the metal-containing medium. Overall, NdTre1 exercises an important immune function in shrimp resistance to metal stimulation by regulating apoptosis and molting. Further investigation can further explore specific response mechanisms of NdTre1 to multiple metals.

Characteristics of anti-contactin1 antibody positive autoimmune nodopathies combined with membranous nephropathy.

BACKGROUND: Autoimmune nodopathy (AN) is a very rare new disease entity, especially when combined with membranous nephropathy (MN). METHODS: Antibodies against nodal-paranodal cell adhesion molecules in the serum were detected using cell-based assays. Antibody subtypes against contactin-1 (CNTN1) were confirmed. Cases of anti-CNTN1 antibody-positive AN with and without MN were retrieved through a literature search to compare clinical and electrophysiological characteristics. RESULTS: A 65-year-old male patient with MN developed limb numbness and weakness, along with walking instability. Serum CNTN1 antibodies were positive, primarily those of the IgG4 subtype. Electromyography showed prominent demyelination patterns in both the proximal and distal segments of the nerves compared to the middle nerve trunk. Magnetic resonance imaging revealed enlargement of the bilateral brachial and lumbosacral plexuses and local hyperintensity of the right C5-C6 nerve roots. Thirty-five cases with anti-CNTN1 antibody-positive AN with MN and 51 cases with anti-CNTN1 antibody-positive AN without MN were compared. Furthermore, the proportion of patients with MN combined with AN presenting with acute or subacute onset was higher than that observed in the MN without AN group. Nevertheless, no substantial differences were noted between the two groups concerning the clinical and electrophysiological characteristics, which were mainly elderly men, manifested as sensory ataxia, IgG4 antibody subtype, electrophysiological demyelination, and a certain effect on immunotherapy. CONCLUSION: In cases of electrophysiological manifestation of demyelinating peripheral neuropathy, especially in distal and poximal segments of nerves, AN should be considered, and further screening for renal function should be performed. Concomitant MN does not aggravate or alleviate peripheral nerve symptoms.

Global prevalence, trend and projection of myopia in children and adolescents from 1990 to 2050: a comprehensive systematic review and meta-analysis.

BACKGROUND: Myopia is a pervasive global public health concern, particularly among the younger population. However, the escalating prevalence of myopia remains uncertain. Hence, our research aims to ascertain the global and regional prevalence of myopia, along with its occurrence within specific demographic groups. METHODS: An exhaustive literature search was performed on several databases covering the period from their inception to 27 June 2023. The global prevalence of myopia was determined by employing pooled estimates with a 95% CI, and further analysis was conducted to assess variations in prevalence estimates across different subgroups. Additionally, a time series model was utilised to forecast and fit accurately the future prevalence of myopia for the next three decades. RESULTS: This study encompasses a comprehensive analysis of 276 studies, involving a total of 5 410 945 participants from 50 countries across all six continents. The findings revealed a gradual increase in pooled prevalence of myopia, ranging from 24.32% (95% CI 15.23% to 33.40%) to 35.81% (95% CI 31.70% to 39.91%), observed from 1990 to 2023, and projections indicate that this prevalence is expected to reach 36.59% in 2040 and 39.80% in 2050. Notably, individuals residing in East Asia (35.22%) or in urban areas (28.55%), female gender (33.57%), adolescents (47.00%), and high school students (45.71%) exhibit a higher proportion of myopia prevalence. CONCLUSION: The global prevalence of childhood myopia is substantial, affecting approximately one-third of children and adolescents, with notable variations in prevalence across different demographic groups. It is anticipated that the global incidence of myopia will exceed 740 million cases by 2050.

Targeting GPX4-mediated ferroptosis protection sensitizes BRCA1-deficient cancer cells to PARP inhibitors.

BRCA1 is one of the most frequently-mutated tumor suppressor genes in ovarian and breast cancers. Loss of BRCA1 triggers homologous recombination (HR) repair deficiency, consequently leading to genomic instability and PARP inhibitors (PARPi)-associated synthetic lethality. Although, the roles of BRCA1 in DNA repair and replication have been extensively investigated, its tumor suppressive functions beyond genome safeguard remain poorly understood. Here, we report that BRCA1 promotes ferroptosis susceptibility through catalyzing K6-linked polyubiquitination of GPX4 and subsequently accelerating GPX4 degradation. Depletion of BRCA1 induces ferroptosis resistance in ovarian cancer cells due to elevated GPX4 protein, and silence of GPX4 significantly suppresses the growth of BRCA1-deficient ovarian cancer xenografts. Importantly, we found that PARPi triggers ferroptosis in ovarian cancer cells, inhibition of GPX4 markedly increase PARPi-induced ferroptosis in BRCA1-deficient ovarian cancer cells. Combined treatment of GPX4 inhibitor and PARPi produces synergistic anti-tumor efficacy in BRCA1-deficient ovarian cancer cells, patient derived organoid (PDO) and xenografts. Thus, our study uncovers a novel mechanism via which BRCA1 exerts tumor suppressive function through regulating ferroptosis, and demonstrates the potential of GPX4 as a therapeutic target for BRCA1-mutant cancers.

Metabolic and Immunological Implications of MME+CAF-Mediated Hypoxia Signaling in Pancreatic Cancer Progression: Therapeutic Insights and Translational Opportunities.

Pancreatic cancer is a devastating malignancy with a high mortality rate, poor prognosis, and limited treatment options. The tumor microenvironment (TME) plays a crucial role in tumor progression and therapy resistance. Multiple subpopulations of cancer-associated fibroblasts (CAFs) within the TME can switch between different states, exhibiting both antitumorigenic and protumorigenic functions in pancreatic cancer. It seems that targeting fibroblast-related proteins and other stromal components is an appealing approach to combat pancreatic cancer. This study employed single-cell transcriptome sequencing to identify MME (Membrane Metalloendopeptidase)-expressing CAFs in pancreatic cancer. Systematic screening was conducted based on tumor differentiation, lymph node metastasis, and T-stage parameters to identify and confirm the existence of a subpopulation of fibroblasts termed MME+CAFs. Subsequent analyses included temporal studies, exploration of intercellular communication patterns focusing on the hypoxia signaling pathway, and investigation of MME+CAF functions in the pancreatic cancer microenvironment. The pathway enrichment analysis and clinical relevance revealed a strong association between high MME expression and glycolysis, hypoxia markers, and pro-cancer inflammatory pathways. The role of MME+CAFs was validated through in vivo and in vitro experiments, including high-throughput drug screening to evaluate potential targeted therapeutic strategies. Single-cell transcriptome sequencing revealed tumor-associated fibroblasts with high MME expression, termed MME+CAF, exhibiting a unique end-stage differentiation function in the TME. MME+CAF involvement in the hypoxia signaling pathway suggested the potential effects on pancreatic cancer progression through intercellular communication. High MME expression was associated with increased glycolysis, hypoxia markers (VEGF), and pro-cancer inflammatory pathways in pancreatic cancer patients, correlating with lower survival rates, advanced disease stage, and higher oncogene mutation rates. Animal experiments confirmed that elevated MME expression in CAFs increases tumor burden, promotes an immunosuppressive microenvironment, and enhances resistance to chemotherapy and immunotherapy. The developed MME+CAF inhibitor IOX2 (a specific prolyl hydroxylase-2 (PHD2) inhibitor), combined with AG (Paclitaxel + Gemcitabine) and anti-PD1 therapy, demonstrated promising antitumor effects, offering a translational strategy for targeting MME in CAFs of pancreatic cancer. The study findings highlighted the significant role of MME+CAF in pancreatic cancer progression by shaping the TME and influencing key pathways. Targeting MME presented a promising strategy to combat the disease, with potential implications for therapeutic interventions aimed at disrupting MME+CAF functions and enhancing the efficacy of pancreatic cancer treatments.