Modulating Nucleation and Crystal Growth of Tin Perovskite Films for Efficient Solar Cells.

The performance of tin halide perovskite solar cells (PSCs) has been severely limited by the rapid crystallization of tin perovskites, which usually leads to an undesirable film quality. In this work, we tackle this issue by regulating the nucleation and crystal growth of tin perovskite films using a small Lewis base additive, urea. The urea-SnI2 interaction facilitates the formation of larger and more uniform clusters, thus accelerating the nucleation process. Additionally, the crystal growth process is extended, resulting in a high-quality tin perovskite film with compact morphology, increased crystallinity, and reduced defects. Consequently, the efficiency of tin PSCs is significantly increased from 10.42% to 14.22%. This work highlights the importance of manipulating the nucleation and crystal growth of tin perovskites to realize efficient tin PSCs.

Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage.

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.

Apigenin suppresses epithelial-mesenchymal transition in high glucose-induced retinal pigment epithelial cell by inhibiting CBP/p300-mediated histone acetylation.

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.

Homogenizing The Low-Dimensional Phases for Stable 2D-3D Tin Perovskite Solar Cells.

2D-3D tin-based perovskites are considered as promising candidates for achieving efficient lead-free perovskite solar cells (PSCs). However, the existence of multiple low-dimensional phases formed during the film preparation hinders the efficient transport of charge carriers. In addition, the non-homogeneous distribution of low-dimensional phases leads to lattice distortion and increases the defect density, which are undesirable for the stability of tin-based PSCs. Here, mixed spacer cations [diethylamine (DEA+) and phenethylamine (PEA+)] are introduced into tin perovskite films to modulate the distribution of the 2D phases. It is found that compared to the film with only PEA+, the combination of DEA+ and PEA+ favors the formation of homogeneous low-dimensional perovskite phases with three octahedral monolayers (n = 3), especially near the bottom interface between perovskite and hole transport layer. The homogenization of 2D phases help improve the film quality with reduced lattice distortion and released strain. With these merits, the tin PSC shows significantly improved stability with 94% of its initial efficiency retained after storing in a nitrogen atmosphere for over 4600 h, and over 80% efficiency maintained after continuous illumination for 400 h.

Ultrahigh Heat/Fire-Resistant, Mechanically Robust, and Closed-Loop Chemical Recyclable Polycarbonate Enabled by Facile Bond Dissociation Energy Modulation.

Plastics serve as an essential foundation in contemporary society. Nevertheless, meeting the rigorous performance demands in advanced applications and addressing their end-of-life disposal are two critical challenges that persist. Here, an innovative and facile method is introduced for the design and scalable production of polycarbonate, a key engineering plastic, simultaneously achieving high performance and closed-loop chemical recyclability. The bisphenol framework of polycarbonate is strategically adjusted from the low-bond-dissociation-energy bisphenol A to high-bond-dissociation-energy 4,4'-dihydroxydiphenyl, in combination with the incorporation of polysiloxane segments. As expected, the enhanced bond dissociation energy endows the polycarbonate with an extremely high glow-wire flammability index surpassing 1025 °C, a 0.8 mm UL-94 V-0 rating, a high LOI value of 39.2%, and more than 50% reduction of heat and smoke release. Furthermore, the π-π stacking interactions within biphenyl structures resulted in a significant enhancement of mechanical strength by as more as 37.7%, and also played a positive role in achieving a lower dielectric constant. Significantly, the copolymer exhibited outstanding closed-loop chemical recyclability, allowing for facile depolymerization into bisphenol monomers and the repolymerized copolymer retains its high heat and fire resistance. This work provides a novel insight in the design of high-performance and closed-loop chemical recyclable polymeric materials.

Histone methyltransferase KMT5C drives liver cancer progression and directs therapeutic response to PARP inhibitors.

BACKGROUND AND AIMS: Epigenetic plasticity is a major challenge in cancer-targeted therapy. However, the molecular basis governing this process has not yet been clearly defined. Despite the considerable success of poly(ADP-ribose) polymerase inhibitors (PARPi) in cancer therapy, the limited response to PARPi, especially in HCC, has been a bottleneck in its clinical implications. Herein, we investigated the molecular basis of the histone methyltransferase KMT5C (lysine methyltransferase 5C) that governs PARPi sensitivity and explored a potential therapeutic strategy for enhancing PARPi efficacy. APPROACH AND RESULTS: We identified KMT5C, a trimethyltransferase of H4K20, as a targetable epigenetic factor that promoted liver tumor growth in mouse de novo MYC/Trp53-/- and xenograft liver tumor models. Notably, induction of KMT5C by environmental stress was crucial for DNA repair and HCC cell survival. Mechanistically, KMT5C interacted with the pivotal component of homologous recombination repair, RAD51, and promoted RAD51/RAD54 complex formation, which was essential for the activation of dsDNA breaks repair. This effect depended on the methyltransferase activity of KMT5C. We further demonstrated that the function of KMT5C in promoting HCC progression was dependent on RAD51. Importantly, either a pharmacological inhibitor (A196) or genetic inhibition of KMT5C sensitized liver cancer cells to PARPi. CONCLUSIONS: KMT5C played a vital role in promoting liver cancer progression by activating the DNA repair response. Our results revealed a novel therapeutic approach using the KMT5C inhibitor A196, concurrent with olaparib, as a potential HCC therapy.

Connection between Mechanical Relaxation and Equilibration Kinetics in a High-Entropy Metallic Glass.

The slow transition from an out-of-equilibrium glass towards a supercooled liquid is a complex relaxation phenomenon. In this Letter, we study the correlation between mechanical relaxation and equilibration kinetics in a Pd_{20}Pt_{20}Cu_{20}Ni_{20}P_{20} high-entropy metallic glass. The evolution of stress relaxation with aging time was obtained with an unprecedented detail, allowing us to pinpoint new interesting features. The long structural relaxation towards equilibrium contains a wide distribution of activation energies, instead of being just associated to the ß relaxation as commonly accepted. The stress relaxation time can be correlated with the equilibration rate and we observe a decrease of microstructural heterogeneity which contrasts with an increase of dynamic heterogeneity. These results significantly enhance our insight of the interplay between relaxation dynamics and thermodynamics in metallic glasses.

Halogen Substitution Regulates High Temperature Dielectric Switch in Lead-Free Chiral Hybrid Perovskites.

Hybrid metal halides (HMHs) based phase transition materials have received widespread attention due to their excellent performance and potential applications in energy harvesting, optoelectronics, ferroics, and actuators. Nevertheless, effectively regulating the properties of phase transitions is still a thorny problem. In this work, two chiral lead-free HMHs (R-3FP)2 SbCl5 (1; 3FP=3-fluoropyrrolidinium) and (R-3FP)2 SbBr5 (2) were synthesized. By replacing the halide ions in the inorganic skeleton, the phase transition temperature of 2 changes with an increase of about 20 K, compared with 1. Meanwhile, both compounds display reversible dielectric switching properties. Through crystal structure analysis and Hirshfeld surface analysis, their phase transitions are ascribed to the disorder of the cations and deformation of the inorganic chains.

A novel long noncoding RNA-lncRNA-AABR07066529.3 alleviates inflammation, apoptosis, and pyroptosis by inhibiting MyD88 in lipopolysaccharide-induced myocardial depression.

Sepsis-induced myocardial depression (SIMD) is common in pediatric intensive care units and seriously threatens children's health. Recently, long noncoding RNAs (lncRNAs) have been showed to play important roles in various diseases; however, its role in SIMD is unclear. In this study, we used lipopolysaccharide (LPS)-treated rats and H9c2 cardiomyocytes to mimic SIMD in vivo and in vitro. We found that the expression of a novel lncRNA, we named lncRNA-AABR07066529.3, was elevated in LPS-induced rat heart tissue and H9c2 cardiomyocytes. In addition, LPS-induced inflammation, apoptosis, and pyroptosis were significantly exacerbated after lncRNA-AABR07066529.3 knockdown. Moreover, we found that myeloid differentiation factor 88 (MyD88) was upregulated in LPS-treated groups and was inhibited by lncRNA-AABR07066529.3. Besides, MyD88 knockdown abolished lncRNA-AABR07066529.3 silencing effects on inflammation, apoptosis, and pyroptosis induced by LPS in H9c2 cardiomyocytes. In our study, we found lncRNA-AABR07066529.3 exerted protective effects on LPS-induced cardiomyocytes by regulating MyD88 and might serve as a potential treatment target for SIMD.

Discovery of L15 as a novel Vif PROTAC degrader with antiviral activity against HIV-1.

Viral infectivity factor (Vif) has been recognized as a new therapeutic target for human immunodeficiency virus-1 (HIV-1) infected patients. In our previous work, we have synthesized a novel class of Vif inhibitors with 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold, which show obvious activity in HIV-1 infected cells and are also effective against drug-resistant strains. Proteolytic targeting chimera (PROTAC) utilizes the ubiquitin-proteasome system to degrade target proteins, which is well established in the field of cancer, but the antiviral PROTAC molecules are rarely reported. In order to explore the effectiveness of PROTAC in the antiviral area, we designed and synthesized a series of degrader of HIV-1 Vif based on 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold. Among them, L15 can degrade Vif protein obviously in a dose-dependent manner and shows certain antivirus activity. Meanwhile, molecular dynamics simulation indicated that the ternary complex formed by L15, Vif, and E3 ligase adopted a reasonable binding mode and maintained a stable interaction. This provided a molecular basis and prerequisite for the selective degradation of the Vif protein by L15. This study reports the HIV-1 Vif PROTAC for the first time and represents the proof-of-concept of PROTACs-based antiviral drug discovery in the field of HIV/ acquired immune deficiency syndrome (AIDS).

The suture fixation of the levonorgestrel-releasing intrauterine device with hysteroscope for the treatment of adenomyosis in patients at high risk of device expulsion-a prospective observational study.

BACKGROUND: This study aimed to investigate the safety and efficacy of suture fixation of the levonorgestrel-releasing intrauterine device (LNG-IUD) by hysteroscope for the treatment of adenomyosis in patients at high risk of device expulsion, to provide a viable treatment option for these patients. METHODS: Twenty-one patients with large symptomatic adenomyosis were sewed and fixed with the LNG-IUD in the uterus by hysteroscopy to prevent the device expulsion. RESULTS: In this prospective case series, all 21 patients were successfully sewed and fixed with the LNG-IUD in the uterus by hysteroscopy. The amount of menstruation was significantly decreased and dysmenorrhea was significantly relieved in 3, 6, and 12 months after surgery compared with before surgery. Only one patient underwent a laparoscopic hysterectomy due to dysmenorrhea which was not alleviated one month later. Serious IUD complications including expulsion and perforation were not observed. There was no development of new side effects than LNG-IUD insertion. CONCLUSION: Our findings indicate that suture fixation of the LNG-IUD by hysteroscope is a safe, effective, and minimally invasive surgical procedure to prevent the device expulsion. It is a good solution for the treatment of large symptomatic adenomyosis and has shown to be effective in managing symptoms related to adenomyosis.

Children weigh internet inaccuracy when trusting in online information.

This study examined whether an internet source's history of inaccuracy influences children's epistemic trust in online information. Chinese children aged 4 to 8 years (N = 84; 41 girls and 43 boys) accessed information on their own from an image-based website, heard information from the internet that was relayed by an adult, or viewed a person in a video providing information without referring to the internet (in a baseline condition). After the internet source provided three obviously inaccurate statements, children significantly reduced their epistemic trust in the internet source regardless of whether they obtained the information through a direct interaction with the internet or it was relayed by an adult. Moreover, the extent of the reduction in trust was comparable to the baseline video condition. Taken together, these findings demonstrate that 4- to 8-year-old children take into account a history of inaccuracy and revise their beliefs in statements from the internet, just as they do when evaluating human informants.

Spatiotemporal expression analysis of jasmonic acid and saponin-related genes uncovers a potential biosynthetic regulation in Panax notoginseng.

BACKGROUND: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones. RESULTS: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways. CONCLUSION: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry.

Ambient Air Processed Inverted Inorganic Perovskite Solar Cells with over 21 % Efficiency Enabled by Multifunctional Ethacridine Lactate.

All-inorganic cesium lead triiodide perovskites (CsPbI3) have attracted increasing attention due to their good thermal stability, remarkable optoelectronic properties, and adaptability in tandem solar cells. However, N2-filled glovebox is generally required to strictly control the humidity during film fabrication due to the moisture-induced black-to-yellow phase transition, which remains a great hinderance for further commercialization. Herein, we report an effective approach via incorporating multifunctional ethacridine lactate (EAL) to mitigate moisture invasion and enable the fabrication of efficient inverted (p-i-n) CsPbI3 perovskite solar cells (PSCs) under ambient condition. It is revealed that the lactate anions accelerate the crystallization of CsPbI3, shortening the exposure time to moisture during film fabrication. Meanwhile, the conjugated backbone and multiple functional groups in the ethacridine cations can interact with I- and Pb2+ to reduce the undesired defects, stabilize the perovskite structure and facilitate the charge transport in the film. Moreover, EAL incorporation also leads to better energy alignment, thus favoring charge extraction at both upper and bottom interfaces. Consequently, the device efficiency and stability are enormously enhanced, with the champion efficiency reaching 21.08 %. This even surpasses the highest value reported for the devices fabricated in glovebox, representing a record efficiency of inverted all-inorganic PSCs.

Distinct Roles of Dopamine Receptor Subtypes in the Nucleus Accumbens during Itch Signal Processing.

Ventral tegmental area (VTA) dopaminergic neurons, which are well known for their central roles in reward and motivation-related behaviors, have been shown to participate in itch processing via their projection to the nucleus accumbens (NAc). However, the functional roles of different dopamine receptor subtypes in subregions of the NAc during itch processing remain unknown. With pharmacological approaches, we found that the blockade of dopamine D1 receptors (D1R), but not dopamine D2 receptors (D2R), in the lateral shell (LaSh) of the NAc impaired pruritogen-induced scratching behavior in male mice. In contrast, pharmacological activation of D2R in both the LaSh and medial shell (MeSh) of the NAc attenuated the scratching behavior induced by pruritogens. Consistently, we found that dopamine release, as detected by a dopamine sensor, was elevated in the LaSh rather than the MeSh of the NAc at the onset of scratching behavior. Furthermore, the elevation of dopamine release in the LaSh of the NAc persisted even though itch-relieving behavior was blocked, suggesting that the dopamine signal in the NAc LaSh represents a motivational component of itch processing. Our study revealed different dynamics of dopamine release that target neurons expressing two dopamine receptors subtypes within different subregions of the NAc, and emphasized that D1R in the LaSh of the NAc is important in itch signal processing.SIGNIFICANCE STATEMENT Dopamine has been implicated in itch signal processing. However, the mechanism underlying the functional role of dopamine in itch processing remains largely unknown. Here, we examined the role of dopamine D1 receptor (D1R) and D2R in the nucleus accumbens (NAc) shell during pruritogen-induced scratching behavior. We demonstrated that D1R in the NAc lateral shell (LaSh) play an important role in motivating itch-induced scratching behavior, while activation of D2R would terminate scratching behavior. Our study revealed the diverse functional roles of dopamine signals in the NAc shell during itch processing.

Liquid-Liquid Phase Separation in Single Suspended Aerosol Microdroplets.

Liquid-liquid phase separation (LLPS) is ubiquitous in ambient aerosols. This specific morphology exerts substantial impacts on the physicochemical properties and atmospheric processes of aerosols, particularly on the gas-particle mass transfer, the interfacial heterogeneous reaction, and the surface albedo. Although there are many studies on the LLPS of aerosols, a clear picture of LLPS in individual aerosols is scarce due to the experimental difficulties of trapping a single particle and mimicking the suspended state of real aerosols. Here, we investigate the phase separation in individual contactless microdroplets by a self-constructed laser tweezer/Raman spectroscopy system. The dynamic transformation of the morphology of optically trapped droplets over the course of humidity cycles is detected by the time-resolved cavity-enhanced Raman spectra. The impacts of pH and inorganic components on LLPS in aerosols are discussed. The results show that the increasing acidity can enhance the miscibility between the hydrophilic and hydrophobic phases and decrease the separation relative humidity of aerosols. Moreover, the inorganic components also have various impacts on the aerosol phase state, whose influence depends on their different salting-out capabilities. It brings possible implications on the morphology of actual atmospheric particles, particularly for those dominated by internal mixtures of inorganic and organic components.

Saikosaponin A triggers cell ferroptosis in hepatocellular carcinoma by inducing endoplasmic reticulum stress-stimulated ATF3 expression.

Ferroptosis is a type of nonapoptotic necrotic cell death characterized by iron-dependent lipid peroxidation. Saikosaponin A (SsA), a natural bioactive triterpenoid saponin extracted from Radix Bupleuri, has shown potent antitumor activity against various tumors. However, the underlying mechanism of the antitumor activity of SsA remains unclear. Here, we discovered that SsA induced HCC cell ferroptosis in vitro and in vivo. Using RNA-sequence analysis, we found that SsA mainly affected the glutathione metabolic pathway and inhibited the expression of cystine transporter solute carrier family 7 member 11 (SLC7A11). Indeed, SsA increased intracellular malondialdehyde (MDA) and iron accumulation, while it decreased the levels of reduced glutathione (GSH) in HCC. Deferoxamine (DFO), ferrostatin-1 (Fer-1) and GSH could rescue SsA-induced cell death, whereas Z-VAD-FMK was found ineffective in inhibiting SsA-induced cell death in HCC. Importantly, our result indicated that SsA induced the expression of activation transcription factor 3 (ATF3). SsA-induced cell ferroptosis and suppression of SLC7A11 are dependent on ATF3 in HCC. Moreover, we revealed that SsA induced ATF3 upregulation via activation of endoplasmic reticulum (ER) stress. Taken together, our findings support that ATF3-dependent cell ferroptosis mediated the antitumor effects of SsA, opening the possibility to explore SsA as a ferroptosis inducer in HCC.

A composite single-nucleotide polymorphism prediction signature for extranodal natural killer/T-cell lymphoma.

Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing nonanthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision making. Data from 722 patients with ENKTL from international centers were analyzed. A 7-SNP-based classifier was constructed using LASSO Cox regression in the training cohort (n = 336) and further validated in the internal testing cohort (n = 144) and in 2 external validation cohorts (n = 142 and n = 100). The 7-SNP-based classifier showed good prognostic predictive efficacy in the training cohort and the 3 validation cohorts. Patients with high- and low-risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all P < .001). The 7-SNP-based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. Application of the 7-SNP-based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significantly improved PFS and OS vs radiotherapy alone in high-risk Ann Arbor stage I patients, whereas there was no statistical difference between the 2 therapeutic modalities among low-risk patients. A nomogram was constructed comprising the classifier and clinicopathological variables; it showed remarkably better predictive accuracy than either variable alone. The 7-SNP-based classifier is a complement to existing risk-stratification systems in ENKTL, which could have significant implications for clinical decision making for patients with ENKTL.

Learning Many-Body Hamiltonians with Heisenberg-Limited Scaling.

Learning a many-body Hamiltonian from its dynamics is a fundamental problem in physics. In this Letter, we propose the first algorithm to achieve the Heisenberg limit for learning an interacting N-qubit local Hamiltonian. After a total evolution time of O(ε^{-1}), the proposed algorithm can efficiently estimate any parameter in the N-qubit Hamiltonian to ε error with high probability. Our algorithm uses ideas from quantum simulation to decouple the unknown N-qubit Hamiltonian H into noninteracting patches and learns H using a quantum-enhanced divide-and-conquer approach. The proposed algorithm is robust against state preparation and measurement error, does not require eigenstates or thermal states, and only uses polylog(ε^{-1}) experiments. In contrast, the best existing algorithms require O(ε^{-2}) experiments and total evolution time. We prove a matching lower bound to establish the asymptotic optimality of our algorithm.

Advanced glycation end-products and its soluble receptor are not independent predictors of incident dysglycaemia or metabolic syndrome in women with polycystic ovary syndrome: a prospective observational study.

BACKGROUND: To evaluate the association of serum advanced glycation end-products (AGEs) and its soluble receptor of AGE (sRAGE) levels with dysglycaemia and metabolic syndrome in women with polycystic ovary syndrome (PCOS). METHODS: This was an analysis of a cohort of women with PCOS who were prospectively recruited for a longitudinal observational study on their endocrine and metabolic profile between January 2010 and December 2013. The association of serum AGEs and sRAGE levels with dysglycaemia and metabolic syndrome at the second-year visit (the index visit) and the sixth-year visit (the outcome visit) were determined. Comparisons of continuous variables between groups were made using the Mann-Whitney U-test. Spearman test was used for correlation analysis. Multivariate binary logistic regression analysis was employed to identify the factors independently associated with the outcome events. RESULTS: A total of 329 women were analysed at the index visit. Significantly lower serum levels of sRAGE (both p < 0.001), but no significant difference in AGEs, were observed in those with dysglycaemia or metabolic syndrome. At the outcome visit, those with incident metabolic syndrome had a significantly lower initial serum sRAGE levels (p = 0.008). The association of serum sRAGE with dysglycaemia and metabolic syndrome at the index visit was no longer significant in multivariate logistic regression after controlling for body mass index, free androgen index and homeostatic model assessment for insulin resistance (HOMA-IR). sRAGE was also not significantly associated with incident metabolic syndrome at the outcome visit on multivariate logistic regression. CONCLUSIONS: Serum sRAGE levels are significantly lower in women with PCOS who have dysglycaemia or metabolic syndrome, and in those developing incident metabolic syndrome in four years. However, it does not have a significant independent association with these outcome measures after adjusting for body mass index, free androgen index and HOMA-IR.