Proteome Characterization of Glaucoma Aqueous Humor.

Glaucoma is the leading cause of irreversible blindness worldwide. The proteome characterization of glaucoma is not clearly understood. A total of 175 subjects, including 57 primary acute angle-closure glaucoma (PAACG), 50 primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG), and 33 cataract patients, were enrolled and comparison proteomic analysis was provided. The samples were randomly divided into discovery group or validation group, whose aqueous humor proteome was analyzed by data-independent acquisition or by parallel reaction monitoring. The common proteome features of three types of glaucoma were immune response, lipid metabolism, and cell death. Three proteins, VTN, SERPIND1, and CD14, showed significant upregulation in glaucoma and could discriminate glaucoma from cataract. Mutual differential proteomic analysis of PAACG, PCACG, and NVG showed different proteome characterization of the three types of glaucoma. NVG was characterized with activated angiogenesis. PAACG was characterized with activation of inflammation response. SERPIND1 was discovered to play vital role in glaucoma occurrences, which is associated with eye transparency decrease and glucose metabolism. This study would provide insights in understanding proteome characterization of glaucoma and benefit the clinical application of AH proteome.

Design of a high-power collimating optical system based on Fresnel lenses.

In light-emitting diode (LED) illumination (e.g., LED maritime lighting for ships), creating a uniform light environment for optical systems is an important challenge. In this study, we present a high-power collimating system based on Fresnel lenses, which allows high-brightness LED illumination in the earlier-mentioned remote distance. The work presented in this article focuses on improving the power, compacting the optical structure, and promoting the brightness of the spot. To prove the claims, the system with a total power of 1 kW is designed. The system consists of a 27 W LED array, a freeform surface lens array, and a confocal Fresnel lens array. In comparison with the traditional optical system, the optical structure shortens from 390 to 120 mm, and the divergent angle decreases from 3° to 2 ° $$ {}^{{}^{\circ}} $$ . Meanwhile, the illuminance of the system is obtained as high as 230 lx at the near field of 200 m and 3.0 lx at the far field of 1.5 nautical miles. This new method provides a practical and effective way to solve the problem of low power, insufficient illuminance, and long optical structure for LED array illumination, which is suitable for remote illumination and guidance of ships.

Sub-10†nm radial resolution achieved by cascading a graded structure outside a spherical hyperlens.

Due to the excellent ability to break the diffraction limit in the subwavelength range, metamaterial-based hyperlens has received extensive attention. Unfortunately, radial resolution of most current hyperlens is not high enough, which is a huge obstacle to the application in 3D super-resolution imaging. In this paper, we propose a theoretical solution to this issue by cascading a graded structure outside the conventional Ag-TiO2 spherical hyperlens. The product of the thickness and the refractive index (RI) of the dielectric layer in the graded structure is fixed to 19.8 while RI increases linearly from 1.38 to 3.54 along the radial direction. By reducing the asymptote slope of the dispersion curve, the coupling of the wave vectors to the hyperlens is enhanced and thus radial resolution is significantly improved to 5 nm while ensuring that the focus is still detectable in the far-field. This design paves the way to high-performance hyperlens for 3D imaging and biosensing in the future.

Topological inverse design of fabrication-constrained nanophotonic devices via an adaptive projection method.

Topology optimization has been widely adopted in the inverse design of nanophotonic devices due to low computation cost, which unfortunately produces intermediate relative permittivity values that fail to meet fabrication constraints. Additionally, the postprocessing required inevitably increases the complexity of the inverse design. In this Letter, we propose an adaptive projection method for topology optimization, in which a two-level hierarchical hyperbolic tangent projection function with linear increment and differentiation is constructed and applied to eliminate inherent defects of conventional topology optimization. Two binarized nanophotonic devices have been designed by our adaptive projection method, among which one ultra-compact dual 90°-bend waveguide reduces the average insertion loss to 20.3% of its similar counterpart and shows an 8.1% reduction for the average crosstalk in the O band, the other ultralow-loss waveguide crossing features an average insertion loss as low as 0.09 dB. With the significant advantages of excellent performance guarantee and fabrication-friendly geometry control fully demonstrated, our inverse design solution shows potential to contribute to nanophotonic devices and integrated chips.

Durably Self-Sustained Droplet on a Fully Miscible Liquid Film.

Droplets impacting onto a solid or liquid surface inducing wetting, floatation, splash, coalescence, etc. is ubiquitous in nature and industrial processes. Here, we report that liquid droplets exhibit spherical caps upon contact with a fully miscible liquid film of lower surface tension, despite the spontaneous mixing of the two liquids. Such a spherical cap on a continuous liquid surface sustains a long lifespan up to minutes before ultimately merging into the film. Benefiting from large viscous forces in a thin film as a result of spatial confinement, the surface flow is substantially suppressed. Therefore, the surface tension gradient responsible for this phenomenon is maintained because the normal diffusion of film liquid into the droplet can timely dilute film liquid supplied by uphill Marangoni flow at the droplet surface. The present finding removes the conventional cognition that droplet coalescence is prompt on fully miscible continuous liquid surfaces, thus benefiting design of new types of microfluidic devices.

Nucleation and dissociation of methane clathrate embryo at the gas-water interface.

Among natural energy resources, methane clathrate has attracted tremendous attention because of its strong relevance to current energy and environment issues. Yet little is known about how the clathrate starts to nucleate and disintegrate at the molecular level, because such microscopic processes are difficult to probe experimentally. Using surface-specific sum-frequency vibrational spectroscopy, we have studied in situ the nucleation and disintegration of methane clathrate embryos at the methane-gas-water interface under high pressure and different temperatures. Before appearance of macroscopic methane clathrate, the interfacial structure undergoes 3 stages as temperature varies, namely, dissolution of methane molecules into water interface, formation of cage-like methane-water complexes, and appearance of microscopic methane clathrate, while the bulk water structure remains unchanged. We find spectral features associated with methane-water complexes emerging in the induction time. The complexes are present over a wide temperature window and act as nuclei for clathrate growth. Their existence in the melt of clathrates explains why melted clathrates can be more readily recrystallized at higher temperature, the so-called "memory effect." Our findings here on the nucleation mechanism of clathrates could provide guidance for rational control of formation and disintegration of clathrates.

Nonadiabatic Dynamics of Photocatalytic Water Splitting on A Polymeric Semiconductor.

To elucidate the nature of light-driven photocatalytic water splitting, a polymeric semiconductor-graphitic carbon nitride (g-C3N4)-has been chosen as a prototype substrate for studying atomistic water spitting processes in realistic environments. Our nonadiabatic quantum dynamics simulations based on real-time time-dependent density functional theory reveal explicitly the transport channel of photogenerated charge carriers at the g-C3N4/water interface, which shows a strong correlation to bond re-forming. A three-step photoreaction mechanism is proposed, whereas the key roles of hole-driven hydrogen transfer and interfacial water configurations were identified. Immediately following photocatalytic water splitting, atomic pathways for the two dissociated hydrogen atoms approaching each other and forming the H2 gas molecule are demonstrated, while the remanent OH radicals may form intermediate products (e.g., H2O2). These results provide critical new insights for the characterization and further development of efficient water-splitting photocatalysts from a dynamic perspective.

Probing Laser-Induced Plasma Generation in Liquid Water.

Understanding photoexcitation dynamics in liquid water is of crucial significance for both fundamental scientific exploration and technological applications. Despite the observations of photoinduced macroscopic phenomena, the initial atomistic movements and associated energy transfer pathways immediately following laser irradiation are hard to track due to the extreme complexity of laser-water interaction and its ultrafast time scale. We explore the femtosecond evolution of liquid water upon intense photoexcitation based on nonadiabatic quantum dynamics simulations. Separate ionic and electronic dynamics were explicitly monitored with tremendous details unveiled on an unprecedented microscopic level. Water was found to undergo the two-step heating processes. The strong-field effects and electronic excitations dominate the first-stage heating and pressurization. Subsequent relaxation of ionic and electronic subsystems further increases the ionic temperature but releases the large internal pressure. The water molecules are stretched during the laser pulses, and the electronic excitations result in the proton transfers after laser pulses. Intense laser pulses violently excite liquid water, giving rise to severe molecular dissociation and plasma generation during the laser pulses. The laser-induced water plasma is characterized by a high fraction of free protons (∼50%), nonequilibrium ionic and electronic distributions, and a metallic electronic density of states.

Two insulin receptors determine alternative wing morphs in planthoppers.

Wing polyphenism is an evolutionarily successful feature found in a wide range of insects. Long-winged morphs can fly, which allows them to escape adverse habitats and track changing resources, whereas short-winged morphs are flightless, but usually possess higher fecundity than the winged morphs. Studies on aphids, crickets and planthoppers have revealed that alternative wing morphs develop in response to various environmental cues, and that the response to these cues may be mediated by developmental hormones, although research in this area has yielded equivocal and conflicting results about exactly which hormones are involved. As it stands, the molecular mechanism underlying wing morph determination in insects has remained elusive. Here we show that two insulin receptors in the migratory brown planthopper Nilaparvata lugens, InR1 and InR2, have opposing roles in controlling long wing versus short wing development by regulating the activity of the forkhead transcription factor Foxo. InR1, acting via the phosphatidylinositol-3-OH kinase (PI(3)K)-protein kinase B (Akt) signalling cascade, leads to the long-winged morph if active and the short-winged morph if inactive. InR2, by contrast, functions as a negative regulator of the InR1-PI(3)K-Akt pathway: suppression of InR2 results in development of the long-winged morph. The brain-secreted ligand Ilp3 triggers development of long-winged morphs. Our findings provide the first evidence of a molecular basis for the regulation of wing polyphenism in insects, and they are also the first demonstration--to our knowledge--of binary control over alternative developmental outcomes, and thus deepen our understanding of the development and evolution of phenotypic plasticity.

Atomically Precise Engineering of Single-Molecule Stereoelectronic Effect.

Charge transport in a single-molecule junction is extraordinarily sensitive to both the internal electronic structure of a molecule and its microscopic environment. Two distinct conductance states of a prototype terphenyl molecule are observed, which correspond to the bistability of outer phenyl rings at each end. An azobenzene unit is intentionally introduced through atomically precise side-functionalization at the central ring of the terphenyl, which is reversibly isomerized between trans and cis forms by either electric or optical stimuli. Both experiment and theory demonstrate that the azobenzene side-group delicately modulates charge transport in the backbone via a single-molecule stereoelectronic effect. We reveal that the dihedral angle between the central and outer phenyl ring, as well as the corresponding rotation barrier, is subtly controlled by isomerization, while the behaviors of the phenyl ring away from the azobenzene are hardly affected. This tunability offers a new route to precisely engineer multiconfigurational single-molecule memories, switches, and sensors.

Calhex231 Alleviates High Glucose-Induced Myocardial Fibrosis via Inhibiting Itch-Ubiquitin Proteasome Pathway in Vitro.

Diabetic cardiomyopathy (DCM) is a major complication of diabetes, and features myocardial fibrosis as its main pathological feature. Calcium sensing receptor (CaSR) is a G protein-coupled receptor, which involves in myocardial fibrosis by regulation of calcium homeostasis. Calhex231, the CaSR inhibitor, is not clear whether it regulates myocardial fibrosis in DCM. In the present study, type 1 diabetic (T1D) rats and primary neonatal rat cardiac fibroblasts were used to observe the role of Calhex231. In vivo experiments showed that in the T1D group, contractile dysfunction and the deposition of collagen I and III were obvious after 12 weeks. In vitro experiments, we found that high glucose (HG) could increase the expression of CaSR, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) collagen I/III, matrix metalloproteinase-2 (MMP-2), MMP9, along with cardiac fibroblast migration and proliferation. We further demonstrated that CaSR activation increased intracellular Ca2+ concentration and upregulated the expression of Itch (atrophin-1 interacting protein 4), which resulted in increasing the ubiquitination levels of Smad7 and upregulating the expression of p-Smad2, p-Smad3. However, treatment with Calhex231 clearly inhibited the above-mentioned changes. Collectively these results suggest that Calhex231 could inhibit Itch-ubiquitin proteasome and TGF-ß1/Smads pathways, and then depress the proliferation of cardiac fibroblasts, along with the reduction deposition of collagen, alleviate glucose-induced myocardial fibrosis. Our findings indicate an important new mechanism for myocardial fibrosis, and suggest Calhex231 would be a new therapeutic agent for the treatment of DCM.

Thickness-Dependent Resistive Switching Behavior of KCu7S4/CuxO/Au Device.

We report the fabrication of KCu7S4/CuxO/Au devices with interfacial CuxO layers of different thicknesses through the spontaneous oxidation of Cu film during deposition. Deposition was conducted with an electron-beam evaporation system under the deposition rate and the chamber pressure of 0.1 Å s-1 and 9.8×10-3 Pa, respectively. X-ray diffraction and X-ray photoelectron spectroscopy characterizations reveal that the interfacial CuxO layers mostly comprise Cu2O and CuO. Electrical characterization reveals that the devices exhibit remarkably thickness-dependent resistive switching behavior. After undergoing an electroforming process under a high compliant current of 1000 µA, the KCu7S4/16 nm CuxO/Au device exhibits stable bipolar resistive switching behavior with the set voltage of 0.58 V and reset voltage of -0.21 V, whereas the KCu7S4/32 nm CuxO/Au device only shows a hysteresis loop in the forward voltage regime. These findings are ascribed to the existence of high-insulation CuO, which is difficult to be softly broken down. Therefore, the depositional condition of Cu film and the thickness of the interfacial layer should be appropriately controlled for the effective performance of devices with Cu electrodes. The results may also provide guidance for the improvement of the performance and stability of Cu-based nonvolatile memory devices.

Hexagonal Monolayer Ice without Shared Edges.

When adsorbed on solids, water molecules are usually arranged into a honeycomb hydrogen-bond network. Here we report the discovery of a novel monolayer ice built exclusively from water hexamers but without shared edges, distinct from all conventional ice phases. Water grown on graphite crystalizes into a robust monolayer ice after annealing, attaining an exceedingly high density of 0.134 Å^{-2}. Unlike chemisorbed ice on metal surfaces, the ice monolayer can translate and rotate on graphite terraces and grow across steps, confirming its two-dimensional nature. First-principles calculations identify the monolayer ice structure as a robust self-assembly of closely packed water hexamers without edge sharing, whose stability is maintained by maximizing the number of intralayer hydrogen bonds on inert surfaces.

Monitoring Local Strain Vector in Atomic-Layered MoSe2 by Second-Harmonic Generation.

Strain serves as a powerful freedom to effectively, reversibly, and continuously engineer the physical and chemical properties of two-dimensional (2D) materials, such as bandgap, phase diagram, and reaction activity. Although there is a high demand for full characterization of the strain vector at local points, it is still very challenging to measure the local strain amplitude and its direction. Here, we report a novel approach to monitor the local strain vector in 2D molybdenum diselenide (MoSe2) by polarization-dependent optical second-harmonic generation (SHG). The strain amplitude can be evaluated from the SHG intensity in a sensitive way (-49% relative change per 1% strain); while the strain direction can be directly indicated by the evolution of polarization-dependent SHG pattern. In addition, we employ this technique to investigate the interlayer locking effect in 2H MoSe2 bilayers when the bottom layer is under stretching but the top layer is free. Our observation, combined with ab initio calculations, demonstrates that the noncovalent interlayer interaction in 2H MoSe2 bilayers is strong enough to transfer the strain of at least 1.4% between the bottom and top layers to prevent interlayer sliding. Our results establish that SHG is an effective approach for in situ, sensitive, and noninvasive measurement of local strain vector in noncentrosymmetric 2D materials.

Brown planthopper nudivirus DNA integrated in its host genome.

UNLABELLED: The brown planthopper (BPH), Nilaparvata lugens (Hemiptera:Delphacidae), is one of the most destructive insect pests of rice crops in Asia. Nudivirus-like sequences were identified during the whole-genome sequencing of BPH. PCR examination showed that the virus sequences were present in all of the 22 BPH populations collected from East, Southeast, and South Asia. Thirty-two of the 33 nudivirus core genes were identified, including 20 homologues of baculovirus core genes. In addition, several gene clusters that were arranged collinearly with those of other nudiviruses were found in the partial virus genome. In a phylogenetic tree constructed using the supermatrix method, the original virus was grouped with other nudiviruses and was closely related to polydnavirus. Taken together, these data indicated that the virus sequences belong to a new member of the family Nudiviridae. More specifically, the virus sequences were integrated into the chromosome of its insect host during coevolution. This study is the first report of a large double-stranded circular DNA virus genome in a sap-sucking hemipteran insect. IMPORTANCE: This is the first report of a large double-stranded DNA virus integrated genome in the planthopper, a plant sap-sucking hemipteran insect. It is an exciting addition to the evolutionary story of bracoviruses (polydnaviruses), nudiviruses, and baculoviruses. The results on the virus sequences integrated in the chromosomes of its insect host also represent a story of successful coevolution of an invertebrate virus and a plant sap-sucking insect.

Preventive mechanisms of Chinese Tibetan medicine Triphala against nonalcoholic fatty liver disease.

BACKGROUND: Triphala (TLP), as a Chinese Tibetan medicine composing of Emblica officinalis, Terminalia chebula and Terminalia bellirica (1.2:1.5:1), exhibited hepatoprotective, hypolipidemic and gut microbiota modulatory effects. Nonetheless, its roles in prevention of high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and the related mechanistic insights involving the interplay of gut microbiota and hepatic inflammation are not known. PURPOSE: The present study seeks to determine if TLP would prevent HFD-induced NAFLD in vivo and its underlying mechanisms from the perspectives of gut microbiota, metabolites, and hepatic inflammation. METHODS: TLP was subjected to extraction and chemo-profiling, and in vivo evaluation in HFD-fed rats on hepatic lipid and inflammation, intestinal microbiota, short-chain fatty acids (SCFAs) and permeability, and body weight and fat content profiles. RESULTS: The TLP was primarily constituted of gallic acid, corilagin and chebulagic acid. Orally administered HFD-fed rats with TLP were characterized by the growth of Ligilactobacillus and Akkermansia, and SCFAs (acetic/propionic/butyric acid) secretion which led to increased claudin-1 and zonula occludens-1 expression that reduced the mucosal permeability to migration of lipopolysaccharides (LPS) into blood and liver. Coupling with hepatic cholesterol and triglyceride lowering actions, the TLP mitigated both inflammatory (ALT, AST, IL-1ß, IL-6 and TNF-α) and pro-inflammatory (TLR4, MYD88 and NF-κB P65) activities of liver, and sequel to histopathological development of NAFLD in a dose-dependent fashion. CONCLUSION: TLP is promisingly an effective therapy to prevent NAFLD through modulating gut microbiota, mucosal permeability and SCFAs secretion with liver fat and inflammatory responses.

Demonstration of a 3D-Assembled Dual-Mode Photodetector Based on Tubular Graphene/III-V Semiconductors Heterostructure and Coplanar Three Electrodes.

3D assembly technology is a cutting-edge methodology for constructing high-performance and multifunctional photodetectors since some attractive photodetection features such as light trapping effect, omnidirectional ability, and high spatial resolution can be introduced. However, there has not been any report of 3D-assembled multimode photodetectors owing to the lack of design and fabrication guideline of electrodes serving for 3D heterostructures. In this study, a 3D-assembled dual-mode photodetector (3DdmPD) was realized successfully via the clever electrical contact between the rolled-up tubular graphene/GaAs/InGaAs heterostructure and planar metal electrode. Arbitrary switching of three coplanar electrodes makes the as-fabricated tubular 3D photodetector work at the unbiased photodiode mode, which is suitable for energy conservation high-speed photodetection, or the biased photoconductive mode, which favors extremely weak light photodetection, fully showing the advantages of multifunctional detection. In more detail, the Ilight/Idark ratio reached as high as 2 × 104, and a responsivity of 42.3 mA/W, a detectivity of 1.5 × 1010 Jones, as well as a rising/falling time (τr/τf) of 360/370 µs were achieved under the self-driven photodiode mode. Excitingly, 3DdmPD shows omnidirectional photodetection ability at the same time. When 3DdmPD works at the photoconductive mode with 5 V bias, its responsivity is extremely high as 7.9 × 104 A/W and corresponding detectivity is increased to 1.0 × 1011 Jones. Benefiting from the totally independent coplanar electrodes, 3DdmPD is much more easily integrated as arrays that are expected to offer the function of high-speed omnidirectional image-sensing with ultralow power consumption than the planar counterparts which share communal bottom electrodes. We believe that our work can contribute to the progress of 3D-assembled optoelectronic devices.

Characterization of alkaloids and phenolics in Nitraria roborowskii Kom. fruit by UHPLC-triple-TOF-MS/MS and its sucrase and maltase inhibitory effects.

Nitraria roborowskii Kom (NRK), with high economic and ecological value, is mainly distributed in the Qaidam Basin, China. However, research on its chemical components and bioactivities is still rare. In this study, its chemical constituents (52) including 10 ß-carboline alkaloids, nine cyclic peptides, three indole alkaloids, five pyrrole alkaloids, eight phenolic acids and 17 flavonoids were identified tentatively using UPLC-triple-TOF-MS/MS. Notablely, one new ß-carboline alkaloid and five new cyclic peptides were confirmed using MS/MS fragmentation pathways. In addition, experiments in vitro indicated that NRK-C had strong maltase and sucrase inhibitory activities (IC50 of 0.202 and 0.103 mg/mL, respectively). Polysaccharide tolerance experiments confirmed NRK-C (400 mg/kg) was associated with decreased postprandial blood glucose (PBG) in diabetic mice. These results suggested that NRK fruit might be used as a functional ingredient in food products.

Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally, the incidence rate and number of patients with nonalcoholic fatty liver disease are increasing, which has become one of the greatest threats to human health. However, there is still no effective therapy and medicine so far. Silphium perfoliatum L. is a perennial herb native to North America, which is used to improve physical fitness and treat liver and spleen related diseases in the traditional medicinal herbs of Indian tribes. This herb is rich in chlorogenic acids, which have the functions of reducing blood lipids, losing weight and protecting liver. However, the effect of these compounds on nonalcoholic fatty liver disease remains unclear. AIM OF THE STUDY: Clarify the therapeutic effects and mechanism of the extract (CY-10) rich in chlorogenic acid and its analogues from Silphium perfoliatum L. on non-alcoholic fatty liver disease, and to determine the active compounds. MATERIALS AND METHODS: A free fatty acid-induced steatosis model of HepG2 cells was established to evaluate the in vitro activity of CY-10 in promoting lipid metabolism. Further, a high-fat diet-induced NAFLD model in C57BL/6 mice was established to detect the effects of CY-10 on various physiological and biochemical indexes in mice, and to elucidate the in vivo effects of the extract on regulating lipid metabolism, anti-inflammation and hepatoprotection, and nontarget lipid metabolomics was performed to analyze differential metabolites of fatty acids in the liver. Subsequently, western blotting and immunohistochemistry were used to analyze the target of the extract and elucidate its mechanism of action. Finally, the active compounds in CY-10 were elucidated through in vitro activity screening. RESULTS: The results indicated that CY-10 significantly attenuated lipid droplet deposition in HepG2 cells. The results of in vivo experiments showed that CY-10 significantly reduce HFD-induced mouse body weight and organ index, improve biochemical indexes, oxidation levels and inflammatory responses in the liver and serum, thereby protecting the liver tissue. It can promote the metabolism of unsaturated fatty acids in the liver and reduce the generation of saturated fatty acids. Furthermore, it is clarified that CY-10 can promote lipid metabolism balance by regulating AMPK/FXR/SREPB-1c/PPAR-γ signal pathway. Ultimately, the main active compound was proved to be cryptochlorogenic acid, which has a strong promoting effect on the metabolism of fatty acids in cells. Impressively, the activities of CY-10 and cryptochlorogenic acid were stronger than simvastatin in vitro and in vivo. CONCLUSION: For the first time, it is clarified that the extract rich in chlorogenic acids and its analogues in Silphium perfoliatum L. have good therapeutic effects on non-alcoholic fatty liver disease. It is confirmed that cryptochlorogenic acid is the main active compound and has good potential for medicine.

Relationship between serum uric acid in early pregnancy and gestational diabetes mellitus: a prospective cohort study.

PURPOSE: The association between serum uric acid (UA) and gestational diabetes mellitus (GDM) was still unclear. Serum UA levels in pregnancy differed from that in non-pregnancy. This study aimed to investigate the changes of serum UA in early pregnancy, and to explore the association of serum UA with the risk of GDM. METHODS: A prospective double-center study including 873 singleton pregnant women was conducted in Beijing, China since 2019 (clinical trial number: NCT03246295). Seventy-eight healthy non-pregnant women were selected to compare the changes of biomarkers in pregnancy. Spearman correlation and logistic regression analysis were performed to measure the relationship between serum UA in early pregnancy and GDM. RESULTS: The incidence of GDM in our cohort was 20.27%(177/873). Compared with non-pregnant women, serum UA and creatinine decreased significantly during early pregnancy. Serum UA concentration in early pregnancy was significantly higher in GDM women than that in normal glucose tolerance (NGT) women [217.0(192.9, 272.0) µmol/l vs. 201.9(176.0, 232.0) µmol/l, p < 0.001]. After adjusted for confounding factors, elevated serum UA remained as an independent risk factor for GDM. The risk of GDM increased when serum UA was above 240 µmol/l (adjusted OR 1.964, 95% CI 1.296-2.977, p < 0.001), and stronger relationships between serum UA and GDM were observed in pregnant women aged over 35 years old and preBMI ≥ 24 kg/m2. CONCLUSION: The normal range of serum UA and creatinine in pregnant women were lower than those in non-pregnant women. It is essential to monitor serum UA concentrations since early pregnancy to alert and prevent GDM, especially in older and heavier pregnant women. CLINICAL TRIAL NUMBER: NCT03246295.