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Diabetic cardiomyopathy (DCM) is a serious complication and death cause of diabetes mellitus (DM). Recent cardiology studies suggest that spermidine has cardioprotective effects. Here, we verified the hypothesis of spermidine's protective effects on DCM. Therefore, db/db mice and primary neonatal mouse cardiomyocytes were used to observe the effects of spermidine. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated in the myocardium of db/db mice, respectively. We found that diabetic mice showed cardiac dysfunction in 12 weeks. Conversely, exogenous spermidine could improve cardiac functions and reduce the deposition of collagens, myocardial damage, reactive oxygen species (ROS) levels and endoplasmic reticulum stress (ERS) in diabetic mouse hearts. Our results also demonstrated that cardiomyocytes displayed ferroptosis and then activated Pannexin-1 expression, which resulted in the increase of the extracellular adenosine triphosphate (ATP). Subsequently, increased ATP as a paracrine molecule combined to purinergic receptor P2X7 (P2X7) to activate ERK1/2 signaling pathway in cardiomyocytes and activated NCOA4-mediated ferroptinophagy to promote lipid peroxidation and ferroptosis. Interestingly, spermidine could reverse these molecular processes. Our findings indicate an important new mechanism for DCM, and suggest spermidine have potential applicability to protect against deterioration of cardiac function with DCM.

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.

Photoexcitation has emerged as an efficient way to trigger phase transitions in strongly correlated materials. There are great controversies about the atomistic mechanisms of structural phase transitions (SPTs) from monoclinic (

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.

Diabetic cardiomyopathy (DCM) is a serious complication and death cause of diabetes mellitus (DM). Recent cardiology studies suggest that spermidine has cardioprotective effects. Here, the hypothesis was tested the spermidine effects of DCM. Therefore, db/db mice and primary neonatal mouse cardiomyocytes were used to observe the effects of spermidine. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated in the myocardium of db/db mice, respectively. We found that diabetic mice showed cardiac dysfunction in 12 weeks. Conversely, exogenous spermidine could improve cardiac functions and reduce the deposition of collagens, myocardial damage, ROS levels and endoplasmic reticulum stress in diabetic mouse hearts. Our results also demonstrated that cardiomyocytes appeared ferroptosis and then activated Pannexin-1 expression, which resulted in increasing the extracellular ATP. Subsequently, increased ATP as a paracrine molecule combined to P2X7 receptors to activate ERK1/2 signaling pathway in cardiomyocytes, and activated NCOA4-mediated ferroptinophagy to promote lipid peroxidation and ferroptosis. Interestingly, spermidine could reverse these molecular processes. Our findings indicate an important new mechanism for DCM, and suggest spermidine have potential applicability to protect against deterioration of cardiac function with DCM.

Tuberous sclerosis complex (TSC) is a rare disease that threatens multiple organs in the human body. TSC‑associated renal angiomyolipoma (TSC‑RAML) has potentially life‑threatening complications and a generally poor prognosis. The present study aimed to find plasma proteomic diagnostics and disease‑associated markers, and explore the tumor microenvironment using multi‑omics. To achieve this goal, the plasma proteomics as well as tissue proteomics, bulk and single‑cell RNA transcriptome from patients with TSC‑RAML were examined and analyzed. The results suggested that plasma proteins such as MMP9 and C‑C motif chemokine ligand 5 were able to differentiate TSC‑RAML from sporadic angiomyolipoma and renal cyst. A correlation analysis revealed that plasma proteomics were associated with lymphangioleiomyomatosis, TSC‑RAML grading and whole‑body disease burden. Tissue proteomics of participants with TSC‑RAML revealed disturbed small molecule catabolic process, mitochondrial matrix component and actin binding function. Bulk and single‑cell RNA sequencing suggested a greater number of tumor‑like cells, fibroblasts and mononuclear macrophages within the tumor microenvironment. The above results indicated that TSC‑RAML exhibited a characteristic and disease‑associated plasma proteomic profile. The unique microenvironment, made up of fibroblasts and mono‑macrophages, may promote tumorigenesis and TSC‑RAML progression.

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.

Determination and conceptualization of atomic structures of metallic glasses or amorphous alloys remain a grand challenge. Structural models proposed for bulk metallic glasses are still controversial owing to experimental difficulties in directly imaging the atom positions in three-dimensional structures. With the advanced atomic-resolution imaging, here we directly observed the atomic arrangements in atomically thin metallic glassy membranes obtained by vapor deposition. The atomic packing in the amorphous membrane is shown to have a fractal characteristic, with the fractal dimension depending on the atomic density. Locally, the atomic configuration for the metallic glass membrane is composed of many types of polygons with the bonding angles concentrated on 45°–55°. The fractal atomic structure is consistent with the analysis by the percolation theory, and may account for the enhanced relaxation dynamics and the easiness of glass transition as reported for the thin metallic glassy films or glassy surface.

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.

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.

Myocardial fibrosis is a major complication of diabetic cardiomyopathy (DCM) that is primarily caused by cardiac fibroblasts that are highly activated by persistent hyperglycemic stimulation, resulting in excessive collagen deposition. Calcium sensing receptor (CaSR) is a member of the G protein‑coupled receptor superfamily and regulates intracellular calcium concentrations, which are associated with numerous diseases, including myocardial infarction, tumors and pulmonary hypertension. However, whether CaSR participates in the pathological process of myocardial fibrosis in DCM remains unknown. The present study aimed to investigate the mechanism via which CaSR regulates high glucose (HG)‑induced cardiac fibrosis in vitro. HG treated‑cardiac fibroblast (CFs) were used and western blotting, immunoprecipitation, Cell Counting Kit‑8 assay, ELISA and transfection technology were performed to examine the role of CaSR. In the HG group, treatment with HG increased CaSR, α‑smooth muscle actin, collagen I/III and matrix metalloproteinase 2/9 expression and enhanced autophagosome generation and CF proliferation. Furthermore, CaSR activation upregulated the expression of Smad ubiquitin regulatory factor 2 (Smurf2), which led to increased intracellular Ca2+ concentrations, increased ubiquitination levels of SKI like proto‑oncogene and Smad7 and autophagy activation. Furthermore, the CaSR agonist (R568) or the CaSR inhibitor (Calhex231) and Smurf2‑small interfering RNA promoted or inhibited HG‑induced alterations, including the enhanced and weakened effects, respectively. Taken together, the results from the present study suggested that increased CaSR expression in CFs activated the Smurf2‑ubiquitin proteasome and autophagy, causing excessive CF proliferation and extensive collagen deposition, which resulted in HG‑induced myocardial fibrosis. These findings indicated a novel pathogenesis of DCM and may provide a novel strategy for the diagnosis and treatment of DCM.

Shuoning Song,1 Yuemei Zhang,2 Xiaolin Qiao,3 Yanbei Duo,1 Jiyu Xu,4 Zhenyao Peng,5 Jing Zhang,6 Yan Chen,3 Xiaorui Nie,3 Qiujin Sun,7 Xianchun Yang,7 Ailing Wang,8 Zechun Lu,8 Wei Sun,4 Yong Fu,1 Yingyue Dong,1 Tao Yuan,1 Weigang Zhao1 1Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Obstetrics, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 3Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 4Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Dean’s Office, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 6Department of Laboratory, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 7Department of Clinical Laboratory, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 8National Center for Women and Children’s Health, China CDC, Beijing, People’s Republic of ChinaCorrespondence: Tao Yuan; Weigang ZhaoDepartment of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86 1069155073Email t75y@sina.com; xiehezhaoweigang@163.comObjective: This study aimed to find the association between alanine transaminase-to-aspartate aminotransferase ratio (ALT/AST) and the incidence of gestational diabetes mellitus (GDM).Methods: A total of 1128 pregnant women were included in this prospective, double-center, observational cohort study. ALT, AST and total bilirubin (TBil) were tested during 6– 12 weeks of gestation and 75-g oral glucose tolerance test (OGTT) was conducted during 24– 28 weeks of gestation to screen GDM. The association between ALT/AST and glucose concentration during OGTT was analyzed by linear regression model. The OR with 95% CI for incidence of GDM associated with ALT/AST was estimated by binary logistic regression. The discriminatory values of ALT/AST and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) for GDM were calculated by the area under the receiver operating characteristic curve (ROC-AUC).Results: The incidence of GDM was 22.07% (249/1128). ALT/AST was higher in GDM group than in NGT group (0.92 [0.75, 1.18] vs 0.80[0.65, 1.02], P < 0.001). ALT/AST had positive correlations with fasting blood glucose, 1-hour and 2-hour blood glucose concentration during OGTT (0.089 [95% CI: 0.034, 0.163], 0.176 [95% CI: 0.052, 0.104], and 0.115 [95% CI: 0.199, 0.609], respectively). The OR of ALT/AST for incidence of GDM was 1.603 (95% CI:1.097, 2.344). The ROC-AUC of ALT/AST and TG/HDL-C reached 0.615 (95% CI: 0.575, 0.655) and 0.619 (95% CI: 0.580, 0.659), respectively.Conclusion: ALT/AST in early pregnancy was an independent risk factor of GDM. The predictive ability of ALT/AST was similar to TG/HDL-C for GDM.Keywords: gestational diabetes mellitus, type 2 diabetes mellitus, alanine transaminase, aspartate aminotransferase, triglyceride

Shuoning Song,1 Yanbei Duo,1 Yuemei Zhang,2 Xiaolin Qiao,3 Jiyu Xu,4 Jing Zhang,5 Zhenyao Peng,6 Yan Chen,3 Xiaorui Nie,3 Qiujin Sun,7 Xianchun Yang,7 Ailing Wang,8 Wei Sun,4 Yong Fu,1 Yingyue Dong,1 Zechun Lu,8 Tao Yuan,1 Weigang Zhao1 1Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Obstetrics, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 3Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 4Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Laboratory, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 6Department of Dean’s Office, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 7Department of Clinical Laboratory, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 8National Center for Women and Children’s Health, China CDC, Beijing, People’s Republic of ChinaCorrespondence: Tao Yuan; Weigang Zhao Email t75y@sina.com; xiehezhaoweigang@163.comObjective: To evaluate the association of hepatic steatosis index (HSI) in the first trimester and the risk of gestational diabetes mellitus (GDM) as well as large for gestational age (LGA) infant in Chinese women.Methods: A total of 1082 pregnant women were included in this study. Maternal basic laboratory data, including ALT, AST, FBG, insulin, TG, and HDL-C, were tested during 6– 12 weeks of gestation and anthropometric characteristics were monitored during gestation. A 75-g oral glucose tolerance test (OGTT) was conducted at 24– 28 weeks of gestation. HSI, nonalcoholic fatty liver disease (NAFLD) liver fat score, triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) and triglyceride-glucose (TyG) index were calculated. Odds ratio with 95% confidence interval for subsequent risk of GDM and LGA by HSI quartiles were assessed by binary logistic regression model. The predictive ability of HSI for GDM and LGA was evaluated by the receiver operating characteristic (ROC) curve analysis and was compared with other indices.Results: The incidence of GDM and LGA were 22.09% (239/1082) and 10.53% (87/826). HSI was higher in GDM group than in NGT group (median, interquartile range: 30.67, 27.20– 35.10 vs 27.98, 25.70– 30.82, P< 0.001). Incidence of GDM was gradually increased with increasing HSI values. Women in the highest HSI quartile had significantly higher risk of LGA delivery than those in the lowest HSI quartile (P< 0.05). The area under the ROC curves of HSI for GDM and LGA were higher than other indices, reaching 0.646 (95%CI: 0.605– 0.686) and 0.600 (95%CI: 0.541– 0.660), respectively.Conclusion: Higher HSI was independently associated with higher risk of GDM and LGA in Chinese women. HSI in the first trimester can predict the risk of GDM and LGA.Keywords: hepatic steatosis index, nonalcoholic fatty liver disease, gestational diabetes mellitus, large for gestational age infant

Objective: To investigate the ability of homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy for predicting gestational diabetes mellitus (GDM) in Chinese women with different first-trimester body mass index (FT-BMI) values. Methods: Baseline characteristics and laboratory tests were collected at the first prenatal visit (6–12 weeks of gestation). GDM was diagnosed by a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. Partial correlation analysis and binary logistic regression were applied to identify the association between HOMA-IR and GDM. The cutoff points for predicting GDM were estimated using receiver operating characteristic (ROC) curve analysis. Results: Of the total of 1343 women, 300 (22.34%) were diagnosed with GDM in the 24–28 weeks of gestation. Partial correlation analysis and binary logistic regression verified HOMA-IR as a significant risk factor for GDM in the normal weight subgroup (FT-BMI < 24 kg/m2) (adjusted OR 2.941 [95% CI 2.153, 4.016], P < 0.001), overweight subgroup (24.0 kg/m2 ≤ FT-BMI < 28.0 kg/m2) (adjusted OR 3.188 [95% CI 2.011, 5.055], P < 0.001), and obese subgroup (FT-BMI ≥ 28.0 kg/m2) (adjusted OR 9.415 [95% CI 1.712, 51.770], p = 0.01). The cutoff values of HOMA-IR were 1.52 (area under the curve (AUC) 0.733, 95% CI 0.701–0.765, p < 0.001) for all participants, 1.43 (AUC 0.691, 95% CI 0.651–0.730, p < 0.001) for normal weight women, 2.27 (AUC 0.760, 95% CI 0.703–0.818, p < 0.001) for overweight women, and 2.31 (AUC 0.801, 95% CI 0.696–0.907, p < 0.001) for obese women. Conclusions: Increased HOMA-IR in early pregnancy is a risk factor for GDM, and HOMA-IR can be affected by body weight. The cutoff value of HOMA-IR to predict GDM should be distinguished by different FT-BMI values.

BACKGROUND: Acute angle-closure glaucoma (AACG) is an ophthalmic emergency that occurs over the course of hours or days and may cause irreversible blindness if not treated immediately. In most cases, optic nerve damage is the cause of visual field (VF) loss in AACG. There has been no reliable biomarker found to evaluate optic nerve damage to date. Aqueous humor (AH) proteome analysis might reveal the proteomic alterations in AACG and provide helpful clues in the search for an AH biomarker of optic nerve damage and VF loss. METHODS: In this study, we used the AH proteome to explore the functions of differentially expressed proteins (DEPs) during disease progression. The AH proteins from the early-stage group and late-stage group were extracted and analyzed by the data-independent acquisition (DIA) method. The DEPs functions were annotated, and parallel reaction monitoring (PRM) was used to validate the key DEPs. RESULTS: A total of 87 DEPs were found. Gene Ontology analysis showed that most DEPs were enriched in immunology, hemodynamics, and apoptosis. Ingenuity pathway analysis found that vascular endothelial growth factor (VEGF) signaling, the production of reactive oxygen species (ROS) in macrophages, and the nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress response were active pathways in the late stage of AACG. The mechanism of retinal ganglion cell (RGC) death was hypothesized on the basis of DEP functional analysis. A total of 20 DEPs were validated by using PRM, and prostaglandin-H2 D-isomerase was found to have the potential to evaluate optic nerve damage. CONCLUSIONS: This study showed that AH proteomic analysis could reveal the proteomic alterations in the pathogenesis of VF loss in AACG and help to provide objective protein biomarkers to evaluate VF loss. These findings will benefit the application of the AH proteome to clinical research.

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.

Water on solid surfaces is essential for a wide range of scientific and technological processes. Previous studies reveal that water molecules on metal surfaces usually form layered structures with ...

Ab initio and classical molecular dynamics simulations show that water can flow through graphdiyne—an experimentally fabricated graphene-like membrane with highly dense (2.4 × 1018 pores/m2), uniformly ordered, subnanometer pores (incircle diameter 0.57 nm and van der Waals area 0.06 nm2). Water transports through subnanopores via a chemical-reaction-like activated process. The activated water flow can be precisely controlled through fine adjustment of working temperature and pressure. In contrast to a linear dependence on pressure for conventional membranes, here pressure directly modulates the activation energy, leading to a nonlinear water flow as a function of pressure. Consequently, high flux (1.6 L/Day/cm2/MPa) with 100% salt rejection efficiency is achieved at reasonable temperatures and pressures, suggesting graphdiyne can serve as an excellent membrane for water desalination. We further show that to get through subnanopores water molecule must break redundant hydrogen bonds to form a two-hydrogen-bond transient structure. Our study unveils the principles and atomistic mechanism for water transport through pores in ultimate size limit, and offers new insights on water permeation through nanochannels, design of molecule sieving and nanofluidic manipulation.

OBJECTIVE To assess the association between insulin resistance and gestational diabetes mellitus (GDM) in early pregnancy and find a simple surrogate index of the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS A total of 700 pregnant women were included in this prospective, double-center, observational cohort study. The glucose and lipid metabolic characterization was performed at 6-12 weeks of pregnancy. All participants underwent a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. Linear regression analysis was applied to find a novel surrogate index of HOMA-IR. Binary logistic analysis was applied to estimate possible associations of different indices with GDM and insulin resistance. RESULTS GDM was diagnosed in 145 of 700 women with singleton pregnancies (20.7%). HOMA-IR was higher in the GDM group than in the normal glucose tolerance (NGT) group and was an individual risk factor for GDM (adjusted risk ratio RR 1.371, 95% confidence interval [CI] 1.129-1.665, P

Two low-energy excitations of a single water molecule are observed via inelastic electron tunneling spectroscopy, where a significant enhancement is achieved by attaching the molecule to the tip apex in a scanning tunneling microscope. Density functional theory simulations and quantum mechanical calculations of an asymmetric top are carried out to reveal the origin of both excitations. Variations in tunneling junction separation give rise to the quantum confinement effect on the quantum state of a water molecule in the tunneling junction. Our results demonstrate a potential method for measuring the dynamic behavior of a single molecule confined in a tunneling junction, where the molecule–substrate interaction can be purposely tuned.

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. Above samples were randomly divided into discovery group or validation group, whose AH proteome were analyzed by data-independent acquisition method or by parallel reaction monitor method. The common proteome features of three types of glaucoma were immune response, lipid metabolism and cell death. Three proteins, VTN, SERPIND1 and CD14, showed significantly up-regulated 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. Funding Statement: This work was supported by the National Key Research and Development Program of China (No. 2016 YFC 1306300, 2018YFC0910202), National Natural Science Foundation of China (No. 30970650, 31200614, 31400669, 81371515, 81170665, 81560121, 81572082), Beijing Natural Science Foundation (No. 7173264, 7172076), Peking Union Medical College Hospital (No.2016-2.27), and Biologic Medicine Information Center of China, National Scientific Data Sharing Platform for Population and Health. Declaration of Interests: All authors have no conflict of interest. Ethics Approval Statement: The study was approved by the Institutional Review Board of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Informed consent was obtained from each participant before enrolment.

Hydrogen gas production from solar water splitting provides a renewable energy cycle to address the grand global energy challenge; however, its dynamics and fundamental mechanism remain elusive. We directly explore by first-principles the ultrafast electron–nuclear quantum dynamics on the time scale of ∼100 fs during water photosplitting on a plasmonic cluster embedded in liquid water. Water molecule splitting is assisted by rapid proton transport in liquid water in a Grotthuss-like mechanism. We identify that a plasmon-induced field enhancement effect dominates water splitting, while charge transfer from gold to the antibonding orbital of a water molecule also plays an important role. “Chain-reaction” like rapid H2 production is observed via the combination of two hydrogen atoms from different water molecules. These results provide a route toward a complete understanding of water photosplitting in the ultimate time and spatial limit.

Purpose The healthy human urine sediment proteome and metaproteome are investigated, to shed light on the variations of urine sediment proteins and metaproteins associated with sex and age. Experimental design Urine sediment samples are collected from 19 healthy subjects. Protein identification and quantification are performed by liquid chromatography coupled high-resolution mass spectrometry. Results A total of 2736 human proteins were identified, which were primarily associated with inflammatory response and energy metabolism. For the metaproteome, 65 genera were identified that were primarily involved in translation and carbohydrate metabolic processes. The median biological coefficient variation of the proteome/metaproteome of human urine sediment was 0.5/0.72, similar to the proteome of human urine supernatant. In addition, sex and age were observed to affect the proteome and metaproteome of healthy human urine sediment. Conclusion and clinical relevance The healthy human urine sediment were characterized, indicating that urine sediment might represent an alternative resource for disease research in addition to urine supernatant, but the influence of sex and age must be considered in the study design process. This article is protected by copyright. All rights reserved.

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 calculat...

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.

Molecular sieving is of great importance to proton exchange in fuel cells, water desalination, and gas separation. Two-dimensional crystals emerge as superior materials showing desirable molecular permeability and selectivity. Here we demonstrate that a graphdiyne membrane, an experimentally fabricated member in the graphyne family, shows superior proton conductivity and perfect selectivity thanks to its intrinsic nanomesh structure. The trans-membrane hydrogen bonds across graphdiyne serve as ideal channels for proton transport in Grotthuss mechanism. The free energy barrier for proton transfer across graphdiyne is ~2.4 kJ mol−1, nearly identical to that in bulk water (2.1 kJ mol−1), enabling “transparent” proton transport at room temperature. This results in a proton conductivity of 0.6 S cm−1 for graphdiyne, four orders of magnitude greater than graphene. Considering its ultimate pore size of 0.55 nm, graphdiyne membrane blocks soluble fuel molecules and exhibits superior proton selectivity. These advantages endow graphdiyne a great potential as proton exchange material., Molecular sieving is important for proton exchange fuel cells, water desalination and gas separation, but achieving optimal proton conductivity and selectivity is difficult. Here the authors use theory to show that a graphdiyne membrane is promising for proton transport in aqueous media at room temperature.

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. Calhex

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., Graphical Abstract, Highlights • Aqueous humor proteome of different glaucoma (PACG, NVG) was profiled. • Potential protein biomarkers for glaucoma were proposed. • Potential mechanism of glaucoma was described. • SERPIND1 was discovered to have potential value for glaucoma diagnosis., In Brief Liu et al. characterized the proteome of aqueous humor from three types of glaucoma. Fifty-seven primary acute angle-closure glaucoma (PAACG), 50 primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG), and 33 cataract patient samples were analyzed using data-independent analysis and parallel reaction monitoring. Lipid metabolism, immune response, and cell death pathways showed different degrees of activation among the three types of glaucoma but were all higher relative to cataract. SERPIND1 was discovered as a vital protein in glaucoma.

Increased nitrogen (N) deposition can affect ecosystem processes and thus influence plant eco-physiological processes in grasslands. However, how N deposition affects eco-physiological processes of leguminous and non-leguminous forbs in alpine grasslands is understudied. A long-term field experiment using a range of simulated N deposition rates (0, 8, 24, 40, 56, and 72 kg N ha−1 year−1) was established to examine the effects of N deposition on various eco-physiological parameters in leguminous and non-leguminous forbs in an alpine meadow of the Qinghai-Tibetan Plateau. We found that the responses of leguminous and non-leguminous forbs to simulated N deposition varied. Net photosynthetic rate of leguminous and non-leguminous forbs exhibited different response patterns, but chronic increases in simulated N deposition rates may lead to negative effects in both functional groups. Neither functional group responded differently in aboveground biomass under the highest N addition level (72 kg N ha−1 year−1) compared to the control. Differences in aboveground biomass of leguminous forbs were observed at intermediate N levels. Short-term simulated N deposition significantly promoted N uptake of both functional groups. In leguminous forbs, simulated N deposition affected net photosynthetic rates (PN) and aboveground biomass (AGB) mainly via stomatal conductance (gs), water use efficiency (WUE), and plant N uptake. In non-leguminous forbs, simulated N deposition affected PN and AGB mainly through WUE and plant N uptake. Our findings suggest that leguminous and non-leguminous forbs have differential response mechanisms to N deposition, and compared with non-leguminous forbs, leguminous forbs are more sensitive to continuing increased N deposition. The obvious decline trend in photosynthetic capacity in leguminous forbs is likely to exacerbate the already divergent ecological processes between leguminous and non-leguminous forbs. More importantly, these changes are likely to alter the future composition, function, and stability of alpine meadow ecosystems.

Water is ubiquitous and so is its presence in the proximity of surfaces. To determine and control the properties of interfacial water molecules at nanoscale is essential for its successful applications in environmental and energy-related fields. It is very challenging to explore the atomic structure and electronic properties of water under various conditions, especially at the surfaces. Here we review recent progress and open challenges in describing physicochemical properties of water on surfaces for solar water splitting, water corrosion, and desalination using first-principles approaches, and highlight the key role of these methods in understanding the complex electronic and dynamic interplay between water and surfaces. We aim at showing the importance of unraveling fundamental mechanisms and providing physical insights into the behavior of water on surfaces, in order to pave the way to water-related material design.