Sorption characteristics of phosphorus on marine sediments in the presence of black carbon derived from fly ash.

The sorption behavior of phosphorus on marine sediments in the presence of black carbon derived from fly ash (FC) was studied. For both the FC and sediment samples, the kinetic curves could be described by a two-compartment first order equation, and the isotherms fit the Freundlich and Langmuir models well. The high specific surface area with abundant acidic functional groups of FC promoted the sorption and make this process more irreversible. The effects were more significant with higher amount of FC added. After sorption, more significant increase in Ex-P, Fe/Al-P and CaP was found in the sediment with FC added, while the organic groups in FC rarely react with phosphorus to form OP. The pH of medium influenced the sorption character, and FC promoted the process significantly at pH < pHPZNPC. The sorption was endothermic with an increase in randomness. The presence of FC had little effects on the thermodynamic parameters.

Targeting a mTOR/autophagy axis: a double-edged sword of rapamycin in spontaneous miscarriage.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

Effective capping of dissolved sulfide generated in Ulva prolifera-rich marine sediments by iron-rich red soil.

Bloom-induced macroalgal enrichment on the seafloor can substantially facilitate dissolved sulfide (DS) production through sulfate reduction. The reaction of DS with sedimentary reactive iron (Fe) is the main mechanism of DS consumption, which however usually could not effectively prevent DS accumulation caused by pulsed macroalgal enrichment. Here we used incubations to investigate the performance of Fe-rich red soil for buffering of DS produced from macroalgae (Ulva prolifera)-enriched sediment. Based on our results, a combination of red soil additions (6.8 kg/m2) before and immediately after pulsed macroalgal deposition (455 g/m2) can effectively cap DS within the red soil layer. The effective DS buffering is mainly due to ample Fe-oxide surface sites available for reaction with DS. Only a small loss (4 %) of buffering capacity after 18-d incubation suggests that the red soil is capable of prolonged DS buffering in macroalgae-enriched sediments.

Innovation network structure, government R&D investment and regional innovation efficiency: Evidence from China.

Based on the panel data of 30 provinces in China from 2011 to 2019, this paper uses a two-stage DEA model to measure regional innovation efficiency, then non-parametric test is used to examine the impact of innovation network structure and government R&D investment on regional innovation efficiency. The results show that, at the provincial level, innovation efficiency of regional R&D is not necessarily in direct proportion to the innovation efficiency in the commercialization stage. Commercialization efficiency is not necessarily high in provinces with high technical R&D efficiency. At the national level, the innovation efficiency gap between our country's R&D and commercialization stage is small, indicating that the development of the national innovation efficiency is more and more balanced. Innovation network structure can promote the R&D efficiency, but has no significant effect on the commercialization efficiency. Government R&D investment helps to improve the R&D efficiency, but it is not conducive to the improvement of commercialization efficiency. The interaction between innovation network structure and government R&D investment will have compound effects on regional innovation efficiency; the region with underdeveloped innovation network structure can increase the government R&D investment to make it have a higher level of R&D. This paper provides insights into how to improve innovation efficiency in different social networks and policy environments.

The Dynamic Changes in the Main Substances in Codonopsis pilosula Root Provide Insights into the Carbon Flux between Primary and Secondary Metabolism during Different Growth Stages.

The dried root of Codonopsis pilosula (Franch.) Nannf., referred to as Dangshen in Chinese, is a famous traditional Chinese medicine. Polysaccharides, lobetyolin, and atractylenolide III are the major bioactive components contributing to its medicinal properties. Here, we investigated the dynamic changes of the main substances in annual Dangshen harvested at 12 time points from 20 May to 20 November 2020 (from early summer to early winter). Although the root biomass increased continuously, the crude polysaccharides content increased and then declined as the temperature fell, and so did the content of soluble proteins. However, the content of total phenolics and flavonoids showed an opposite trend, indicating that the carbon flux was changed between primary metabolism and secondary metabolism as the temperature and growth stages changed. The changes in the contents of lobetyolin and atractylenolide III indicated that autumn might be a suitable harvest time for Dangshen. The antioxidant capacity in Dangshen might be correlated with vitamin C. Furthermore, we analyzed the expression profiles of a few enzyme genes involved in the polysaccharide biosynthesis pathways at different growth stages, showing that CpUGpase and CPPs exhibited a highly positive correlation. These results might lay a foundation for choosing cultivars using gene expression levels as markers.

Overexpression of SmLAC25 promotes lignin accumulation and decreases salvianolic acid content in Salvia miltiorrhiza.

Laccase (LAC) is a blue multicopper oxidase that contains four copper ions, which is involved in lignin polymerization and flavonoid biosynthesis in plants. Although dozens of LAC genes have been identified in Salvia miltiorrhiza Bunge (a model medicinal plant), most have not been functionally characterized. Here, we explored the expression patterns and the functionality of SmLAC25 in S. miltiorrhiza. SmLAC25 has a higher expression level in roots and responds to methyl jasmonate, auxin, abscisic acid, and gibberellin stimuli. The SmLAC25 protein is localized in the cytoplasm and chloroplasts. Recombinant SmLAC25 protein could oxidize coniferyl alcohol and sinapyl alcohol, two monomers of G-lignin and S-lignin. To investigate its function, we generated SmLAC25-overexpressed S. miltiorrhiza plantlets and hairy roots. The lignin content increased significantly in all SmLAC25-overexpressed plantlets and hairy roots, compared with the controls. However, the concentrations of rosmarinic acid and salvianolic acid B decreased significantly in all the SmLAC25-overexpressed lines. Further studies revealed that the transcription levels of some key enzyme genes in the lignin synthesis pathway (e.g., SmCCR and SmCOMT) were significantly improved in the SmLAC25-overexpressed lines, while the expression levels of multiple enzyme genes in the salvianolic acid biosynthesis pathway were inhibited. We speculated that the overexpression of SmLAC25 promoted the metabolic flux of lignin synthesis, which resulted in a decreased metabolic flux to the salvianolic acid biosynthesis pathway.

Sorption and distribution performance of organophosphorus compound (Adenosine 5'-monophosphate)on marine sediments.

In this paper, the kinetics and thermodynamics of Adenosine 5'-monophosphate (AMP) sorption on the sediments obtained from the Yangtze River Estuary and adjacent areas were studied, in combination with the effects of the sediments' properties and media conditions. The kinetics curves could be described by a two-compartment first-order equation, and the equilibrium isotherms fitted well with the modified Langmuir and Freundlich models. The analysis of organic phosphorus (OP) fractions changes after sorption indicated that the contents of exchangeable or loosely sorbed PO increased most significantly. Higher organic matter (OM) of the sediments were favorable for the sorption ability. It was also found that the content of OP and OM in the sediments showed an obvious positive correlation, indicating that organic matter rather than Fe/Al oxides played an important role in the migration of OP in the Yangtze River estuary and its adjacent area. Temperature, salinity and pH of the media influenced the sorption of AMP significantly. Increase of temperature was of benefit to the sorption of AMP, which was a spontaneous and exothermic process according to the calculations of the thermodynamic parameters. The sorption capacity was higher at a moderate salinity in the range of our study. With the pH changing from 3 to 10, the sorption capacity exhibited as a "U-trend" curve.

FvWRKY48 binds to the pectate lyase FvPLA promoter to control fruit softening in Fragaria vesca.

The regulatory mechanisms that link WRKY gene expression to fruit ripening are largely unknown. Using transgenic approaches, we showed that a WRKY gene from wild strawberry (Fragaria vesca), FvWRKY48, may be involved in fruit softening and ripening. We showed that FvWRKY48 is localized to the nucleus and that degradation of the pectin cell wall polymer homogalacturonan, which is present in the middle lamella and tricellular junction zones of the fruit, was greater in FvWRKY48-OE (overexpressing) fruits than in empty vector (EV)-transformed fruits and less substantial in FvWRKY48-RNAi (RNA interference) fruits. Transcriptomic analysis indicated that the expression of pectate lyase A (FvPLA) was significantly downregulated in the FvWRKY48-RNAi receptacle. We determined that FvWRKY48 bound to the FvPLA promoter via a W-box element through yeast one-hybrid, electrophoretic mobility shift, and chromatin immunoprecipitation quantitative polymerase chain reaction experiments, and ß-glucosidase activity assays suggested that this binding promotes pectate lyase activity. In addition, softening and pectin degradation were more intense in FvPLA-OE fruit than in EV fruit, and the middle lamella and tricellular junction zones were denser in FvPLA-RNAi fruit than in EV fruit. We speculated that FvWRKY48 maybe increase the expression of FvPLA, resulting in pectin degradation and fruit softening.

Diagnosing early scar pregnancy in the lower uterine segment after cesarean section by intracavitary ultrasound.

BACKGROUND: Early scar pregnancy (CSP) in the lower uterine segment after cesarean section is a type of ectopic pregnancy that can cause major complications if left untreated. Transabdominal ultrasound is a common procedure but is influenced by external factors. Thus, intracavitary ultrasound may have better diagnostic efficiency for CSP. AIM: To assess the value of intracavitary ultrasound for diagnosing CSP in the lower uterine segment after cesarean section. METHODS: Patients diagnosed with CSP in our hospital from October 2019 to April 2021 were recruited. Transabdominal and intracavitary ultrasound examinations were performed to compare the diagnostic differences for CSP and its types. RESULTS: Sixty-three patients were diagnosed during the study period. The diagnostic accuracy for CSP was higher in intracavitary ultrasound (96.83%) than in transabdominal ultrasound (84.13%) (P < 0.05). The missed diagnosis and misdiagnosis rates did not differ among the ultrasound types (intra: 0.00% and 3.17%; trans: 4.76% and 11.11%, respectively; P > 0.05). For the diagnostic rates for the CSP types, the rates for gestational sac (100.00% vs 90.48%), heterogeneous mass (93.75% vs 75.00%), and part of the uterine cavity (80.00% vs 60.00%) were higher in intracavitary ultrasound than in transabdominal ultrasound, but the difference was not statistically significant (P > 0.05). For gestational sac CSP patients, intracavitary ultrasound showed that the gestational sac was located in the lower uterine segment scar with abundant peripheral blood flow; the distance between the gestational sac and the serosal layer was 2.42 ± 0.50 cm. Intracavitary ultrasound for heterogeneous mass CSP patients indicated that the mass mainly occurred in the lower anterior uterine wall, protruding into the bladder, and was surrounded by abundant internal and peripheral blood flow; the distance between the mass and serosal layer was 1.79 ± 0.30 cm. For CSP type partly located in the uterine cavity, the gestational sac was partly located in the lower uterine cavity and partly in the scar with abundant internal and peripheral blood flow; the distance between the gestational sac and the serosal layer was 2.29 ± 0.28 cm. CONCLUSION: Intracavitary ultrasound had a higher diagnostic accuracy and application value for diagnosing CSP than transabdominal ultrasound, with reduced risk of missed diagnoses and misdiagnosis, thereby preventing delayed treatment.

SmSPL6 Induces Phenolic Acid Biosynthesis and Affects Root Development in Salvia miltiorrhiza.

Salvia miltiorrhiza is a renowned model medicinal plant species for which 15 SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family genes have been identified; however, the specific functions of SmSPLs have not been well characterized as of yet. For this study, the expression patterns of SmSPL6 were determined through its responses to treatments of exogenous hormones, including indole acetic acid (IAA), gibberellic acid (GA3), methyl jasmonic acid (MeJA), and abscisic acid (ABA). To characterize its functionality, we obtained SmSPL6-ovexpressed transgenic S. miltiorrhiza plants and found that overexpressed SmSPL6 promoted the accumulation of phenolic acids and repressed the biosynthesis of anthocyanin. Meanwhile, the root lengths of the SmSPL6-overexpressed lines were significantly longer than the control; however, both the fresh weights and lateral root numbers decreased. Further investigations indicated that SmSPL6 regulated the biosynthesis of phenolic acid by directly binding to the promoter regions of the enzyme genes Sm4CL9 and SmCYP98A14 and activated their expression. We concluded that SmSPL6 regulates not only the biosynthesis of phenolic acids, but also the development of roots in S. miltiorrhiza.

SmbHLH53 is relevant to jasmonate signaling and plays dual roles in regulating the genes for enzymes in the pathway for salvianolic acid B biosynthesis in Salvia miltiorrhiza.

Basic helix-loop-helix (bHLH) transcription factors play essential roles in myriad regulatory processes, including secondary metabolism. In this study with Salvia miltiorrhiza, we isolated and characterized SmbHLH53, which encodes a bHLH family member. Expression of this gene was significantly induced by wounding and multiple hormones, including methyl jasmonic acid; transcript levels were highest in the leaves and roots. Phylogenetic analysis indicated that SmbHLH53 clusters withAtbHLH17 and AtbHLH13, two negative regulators of jasmonate (JA) responses, and is localized in the nucleus and cell membrane. Yeast two-hybrid and bimolecular fluorescent complementation assays indicated that SmbHLH53 forms a homodimer as well as a heterodimer with SmbHLH37. It also interacts with both SmJAZs1/3/8 and SmMYC2, the core members of the JA signal pathway. Unexpectedly, we noted that overexpression of SmbHLH53 did not significantly influence the concentrations of rosmarinic acid and salvianolic acid B in transgenic plants. Results from yeast one-hybrid assays showed that SmbHLH53 binds to the promoters of SmTAT1, SmPAL1, and Sm4CL9, the key genes for enzymes in the pathway for phenolic acid synthesis. Assays of transient transcriptional activity demonstrated that SmbHLH53 represses the promoter of SmTAT1 while activating the promoter of Sm4CL9. Thus, the present work revealed that SmbHLH53 may play dual roles in regulating the genes for enzymes in the pathway for Sal B biosynthesis.

Genome-wide identification and expression analysis of the superoxide dismutase (SOD) gene family in Salvia miltiorrhiza.

Adverse environmental conditions, such as salinity, cold, drought, heavy metals, and pathogens affect the yield and quality of Salvia miltiorrhiza, a well-known medicinal plant used for the treatment of cardiovascular and cerebrovascular diseases. Superoxide dismutase (SOD), a key enzyme of antioxidant system in plants, plays a vital role in protecting plants against various biotic and abiotic stresses via scavenging the reactive oxygen species produced by organisms. However, little is known about the SOD gene family in S. miltiorrhiza. In this study, eight SOD genes, including three Cu/Zn-SODs, two Fe-SODs and three Mn-SODs, were identified in the S. miltiorrhiza genome. Their gene structures, promoters, protein features, phylogenetic relationships, and expression profiles were comprehensively investigated. Gene structure analysis implied that most SmSODs have different introns/exons distrbution patterns. Many cis-elements related to different stress responses or plant hormones were found in the promoter of each SmSOD. Expression profile analysis indicated that SmSODs exhibited diverse responses to cold, salt, drought, heavy metal, and plant hormones. Additionally, 31 types of TFs regulating SmSODs were predicted and analyzed. These findings provided valuable information for further researches on the functions and applications of SmSODs in S. miltiorrhiza growth and adaptation to stress.

Long-term study on the osteogenetic capability and mechanical behavior of a new resorbable biocomposite anchor in a canine model.

BACKGROUND: Biodegradable suture anchors are commonly used for repairing torn rotator cuffs, but these biodegradable materials still suffer from low mechanical strength, poor osteointegration, and the generation of acidic degradation byproducts. METHOD: The purpose of this study was to evaluate the long-term mechanical behavior and osteogenetic capabilities of a biocomposite anchor injection molded with 30% ß-tricalcium phosphate microparticles blended with 70% poly (L-lactide-co-glycolide) (85/15). This study investigated in vitro degradation and in vivo bone formation in a canine model. The initial mechanical behavior, mechanical strength retention with degradation time, and degradation features were investigated. RESULTS: The results showed that the biocomposite anchor had sufficient initial mechanical stability confirmed by comparing the initial shear load on the anchor with the minimum shear load borne by an ankle fracture fixation screw, which is considered a worst-case implantation site for mechanical loading. The maximum shear load retention of the biocomposite anchor was 83% at 12 weeks, which is desirable, as it aligns with the rate of bone healing. The ß-tricalcium phosphate fillers were evenly dispersed in the polymeric matrix and acted to slow the degradation rate and improve the mechanical strength of the anchor. The interface characteristics between the ß-tricalcium phosphate particles and the polymeric matrix changed the degradation behavior of the biocomposite. Phosphate buffer saline was shown to diffuse through the interface into the biocomposite to inhibit the core accelerated degradation rate. In vivo, the addition of ß-tricalcium phosphate induced new bone formation. The biocomposite material developed in this study demonstrated improved osteogenesis in comparison to a plain poly (L-lactide-co-glycolide) material. Neither anchor produced adverse tissue reactions, indicating that the biocomposite had favorable biocompatibility following long-term implantation. CONCLUSION: In summary, the new biocomposite anchor presented in this study had favorable osteogenetic capability, mechanical property, and controlled degradation rate for bone fixation. TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The new biocomposite anchor had sufficient initial and long-term fixation stability and bone formation capability in the canine model. It is indicated that the new biocomposite anchor has a â€‹potential for orthopedic application.

A pilot study of ultrasound-guided acupotomy for the treatment of frozen shoulder.

This study retrospectively analyzed the feasible effectiveness of ultrasound-guided acupotomy (USGAP) for the treatment of frozen shoulder (FS). A total of 36 patients with FS were analyzed in this retrospective study. All 36 patients received extracorporeal shock-wave therapy (ESWT). In addition, 18 of them also underwent USGAP intervention and were assigned to a treatment group, while the other 18 patients did not receive such intervention and were assigned to a control group. The primary efficacy endpoint was pain intensity, as measured by the Numeric Rating Scale (NRS). The secondary efficacy endpoint was assessed by the score of shoulder pain and disability index (SPADI). Furthermore, the adverse events were also documented during the treatment period. All efficacy endpoints were measured after the treatment. After treatment, patients who received USGAP exerted better efficacy endpoints in pain relief, as measured by NRS scale (P < .01), and shoulder disorders, as evaluated by SPADI (P < .01), than subjects who did not receive USGAP. Additionally, no adverse events occurred in either group. The results of this study indicated that USGAP may be used for the treatment of FS effectively. More studies are still needed to warrant the present results.

Effect of black carbon on sorption and desorption of phosphorus onto sediments.

The sorption behavior of phosphorus onto sediment was investigated with the addition of BC derived from incomplete biomass combustion (PC). The sorption kinetic curves of phosphorus onto PC and sediment could be described by a two-compartment first order equation, and the sorption isotherms fit the Freundlich model well. With increasing amounts of PC added, the sorption capacity increased while the HI did not change much. The distribution of phosphorus forms showed that CaP (ACa-P plus DAP) constituted the highest fraction in the sediment samples. Throughout the sorption process, CaP and OP changed very little, but the Ex-P and FeP increased obviously, and the presence of PC made this increase more significantly. The high specific area and the presence of iron and aluminum, as well as the modification of the sediments surface properties, make the addition of PC be favorable for the sorption of phosphorus onto sediments.

Polylactide Composite Pins Reinforced with Bioresorbable Continuous Glass Fibers Demonstrating Bone-like Apatite Formation and Spiral Delamination Degradation.

The emergence of polylactide composites reinforced with bioresorbable silicate glass fibers has allowed for the long-term success of biodegradable polymers in load-bearing orthopedic applications. However, few studies have reported on the degradation behavior and bioactivity of such biocomposites. The aim of this work was to investigate the degradation behavior and in vitro bioactivity of a novel biocomposite pin composed of bioresorbable continuous glass fibers and poly-L-D-lactide in simulated body fluid for 78 weeks. As the materials degraded, periodic spiral delamination formed microtubes and funnel-shaped structures in the biocomposite pins. It was speculated that the direction of degradation, from both ends towards the middle of the fibers and from the surface through to the bulk of the polymer matrix, could facilitate bone healing. Following immersion in simulated body fluid, a bone-like apatite layer formed on the biocomposite pins which had a similar composition and structure to natural bone. The sheet- and needle-like apatite nanostructure was doped with sodium, magnesium, and carbonate ions, which acted to lower the Ca/P atomic ratio to less than the stoichiometric apatite and presented a calcium-deficient apatite with low crystallinity. These findings demonstrated the bioactivity of the new biocomposite pins in vitro and their excellent potential for load-bearing applications.

GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca2+ signalling in a GABA-independent manner.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis. METHODS: The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism. RESULTS: GABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression. CONCLUSIONS: Overexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC.

Targeting Purinergic Receptor P2Y2 Prevents the Growth of Pancreatic Ductal Adenocarcinoma by Inhibiting Cancer Cell Glycolysis.

PURPOSE: Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to prevent cancer progression. We aimed to determine whether blocking extracellular ATP-P2RY2 axis could be a potential therapeutic approach for PDAC treatment. EXPERIMENTAL DESIGN: Expression of P2RY2 was determined in 264 human PDAC samples and correlated to patient survival. P2RY2 was inhibited in human PDAC cell lines by antagonist and shRNA, respectively, and cell viability, clonogenicity, and glycolysis were determined. RNA sequencing of PDAC cell line was applied to reveal underlying molecular mechanisms. Multiple PDAC mouse models were used to assess the effects of the P2RY2 inhibition on PDAC progression. RESULTS: P2RY2 was upregulated and associated with poor prognosis in PDAC. Activated P2RY2 by increased extracellular ATP in tumor microenvironment promoted PDAC growth and glycolysis. Further studies showed that the agonist-activated P2RY2 triggered PI3K/AKT-mTOR signaling by crosstalk with PDGFR mediated by Yes1, resulting in elevated expression of c-Myc and HIF1α, which subsequently enhanced cancer cell glycolysis. Genetic and pharmacologic inhibition of P2RY2 impaired tumor cell growth in subcutaneous and orthotopic xenograft model, as well as delayed tumor progression in inflammation-driven PDAC model. In addition, synergy was observed when AR-C118925XX, the selective antagonist of P2RY2 receptor, and gemcitabine were combined, resulting in prolonged survival of xenografted PDAC mice. CONCLUSIONS: These findings reveal the roles of the P2RY2 in PDAC metabolic reprogramming, suggesting that P2RY2 might be a potential metabolic therapeutic target for PDAC.