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.

The Association of Hematological Parameters in Early and Middle Pregnancy with the Risk of Gestational Diabetes Mellitus.

Objective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6-12 weeks of gestation) to the second trimester (24-28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM. Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM. Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy. Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.

Multi-omics analyses reveal bacteria and catalase associated with keloid disease.

BACKGROUND: The pathology of keloid and especially the roles of bacteria on it were not well understood. METHODS: In this study, multi-omics analyses including microbiome, metaproteomics, metabolomic, single-cell transcriptome and cell-derived xenograft (CDX) mice model were used to explore the roles of bacteria on keloid disease. FINDINGS: We found that the types of bacteria are significantly different between keloid and healthy skin. The 16S rRNA sequencing and metaproteomics showed that more catalase (CAT) negative bacteria, Clostridium and Roseburia existed in keloid compared with the adjacent healthy skin. In addition, protein mass spectrometry shows that CAT is one of the differentially expressed proteins (DEPs). Overexpression of CAT inhibited the proliferation, migration and invasion of keloid fibroblasts, and these characteristics were opposite when CAT was knocked down. Furthermore, the CDX model showed that Clostridium butyricum promote the growth of patient's keloid fibroblasts in BALB/c female nude mice, while CAT positive bacteria Bacillus subtilis inhibited it. Single-cell RNA sequencing verified that oxidative stress was up-regulated and CAT was down-regulated in mesenchymal-like fibroblasts of keloid. INTERPRETATION: In conclusion, our findings suggest that bacteria and CAT contribute to keloid disease. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

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.

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.

Free time-induced retroactive effects in working memory: Evidence from the single-gap paradigm.

Free time in a working memory task often improves the recall performances of the to-be-remembered items. It is still debated whether the free-time effect in working memory is purely proactive, purely retroactive, or both proactive and retroactive. In the present study, we used the single-gap paradigm to explore this question. In Experiment 1, we measured the gap-length effect (i.e., the difference in memory performance elicited by the gap-length difference) under three long-short-gap combinations (i.e., 2,500 ms/100 ms, 2,500 ms/500 ms, 2,500 ms/1,000 ms). Proactive effects have been observed in all the three combinations whereas retroactive effects have only been found in two of them (i.e., 2,500 ms/100 ms, 2,500 ms/500 ms). To rule out the possibility that the retroactive effects found in Experiment 1 were simply due to the temporal grouping caused by the gap, in Experiment 2, the 2,500 ms/500 ms combination was retested, with the memory materials being changed from letters (the material used in Experiment 1) to words. The results showed that the range of the retroactive effect (i.e., the number of affected memory items prior to the gap) increased when the memory material changed from letters to words, which cannot be explained by temporal grouping. Taken together, the two experiments provided solid evidence that free time in working memory could produce both retroactive and proactive effects that cannot be explained by temporal grouping. These findings also provide insight into the underlying mechanism of working memory, for example, whether rehearsal would occur during the free time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

A Simplified Screening Model to Predict the Risk of Gestational Diabetes Mellitus in Pregnant Chinese Women.

INTRODUCTION: This study aimed to develop a simplified screening model to identify pregnant Chinese women at risk of gestational diabetes mellitus (GDM) in the first trimester. METHODS: This prospective study included 1289 pregnant women in their first trimester (6-12 weeks of gestation) with clinical parameters and laboratory data. Logistic regression was performed to extract coefficients and select predictors. The performance of the prediction model was assessed in terms of discrimination and calibration. Internal validation was performed through bootstrapping (1000 random samples). RESULTS: The prevalence of GDM in our study cohort was 21.1%. Maternal age, prepregnancy body mass index (BMI), a family history of diabetes, fasting blood glucose levels, the alanine transaminase to aspartate aminotransferase ratio (ALT/AST), and the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were selected for inclusion in the prediction model. The Hosmer-Lemeshow goodness-of-fit test showed good consistency between prediction and actual observation, and bootstrapping indicated good internal performance. The area under the receiver operating characteristic curve (ROC-AUC) of the multivariate logistic regression model and the simplified clinical screening model was 0.825 (95% confidence interval [CI] 0.797-0.853, P < 0.001) and 0.784 (95% CI 0.750-0.818, P < 0.001), respectively. The performance of our prediction model was superior to that of three other published models. CONCLUSION: We developed a simplified clinical screening model for predicting the risk of GDM in pregnant Chinese women. The model provides a feasible and convenient protocol to identify women at high risk of GDM in early pregnancy. Further validations are needed to evaluate the performance of the model in other populations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03246295.

Proteomic Study of Middle Ear Effusion and Its Clinical Application for Otitis Media with Effusion.

Background: Proteins found in middle ear effusion play crucial roles in the physiological and pathological processes of otitis media with effusion (OME), influencing the etiology and clinical characteristics of this disease. The qualitative and quantitative composition of these proteins depending on the underlying pathogenesis of middle ear effusion. Understanding their physiological and pathological functions is of great importance. Methods: We collected samples from 19 volunteers diagnosed with OME. After offline separation using high-pH reversed-phase liquid chromatography (RPLC), the pooled sample was subjected to LC-MS/MS analysis to obtain a comprehensive profile of the OME proteome. Functional analysis was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) annotations. Data-independent acquisition (DIA) technology was utilized to analyze samples and fix whether the OME proteome could replicate the pathophysiological features associated with this disease. We conducted a differential proteomic analysis between patients with simple OME and patients who had received radiotherapy. The radiotherapy-reduced group was further divided into two subgroups: nasopharyngeal carcinoma (NPC) and other types of carcinoma. Parallel reaction monitoring (PRM) technology was used for validation of 36 differentially expressed proteins (DEPs). Results: A number of 732 proteins were identified in the OME proteome database. Among them, 527 proteins were quantified using peak intensity-based semi-quantification (iBAQ), covering a wide dynamic range of approximately 8 orders of magnitude. Based on the functional analysis, we proposed a hypothetical mechanism of OME. Conclusion: This study managed to put up an inclusive analysis of the OME proteome, establishing the first human OME proteome database. We focused on differential proteomic analysis among different groups to gain a more comprehensive concept of the OME proteome and search for meaningful biomarkers.

Inhibitory activities and rules of plant gallotannins with different numbers of galloyl moieties on sucrase, maltase and α-amylase in vitro and in vivo.

BACKGROUND: α-Glucosidase inhibitors could effectively reduce postprandial blood glucose (PBG) levels and control the occurrence of complications of diabetes. Gallotannins (GTs) in plants have attracted much attention due to their significant α-glucosidase inhibitory activities in vitro. However, there is still a lack of systematic comparative studies to further elucidate inhibitory activities in vivo and in vitro of these compounds against α-glucosidase, especially for mammalian sucrase and maltase, and analyze their structure-activity relationship. PURPOSE: Determine the in vitro and in vivo inhibitory activities of five GTs with different number of galloyl moieties (GMs) on sucrase, maltase and α-amylase, and elucidate the relationship between α-glucosidase inhibitory activities and the number and connection mode of GMs. METHODS: Molecular docking and dynamics were used to study the binding mode and binding ability of five GTs against sucrase, maltase and α-amylase. Then, the inhibitory activities and inhibitory mechanisms of these compounds on sucrase, maltase and α-amylase in vitro were studied using inhibitory assay and enzyme inhibition kinetics. Further, the hypoglycemic effects in vivo of these compounds were demonstrated by three polysaccharides tolerance experiments on diabetes model mice. RESULTS: The results of molecular docking showed that these compounds could bind to enzymes through hydrogen bonds, hydrophobic interactions, etc. In addition, the α-glucosidase inhibition comparative studies in vitro and in vivo demonstrated that the inhibitory activities of these compounds on all three sucrase, maltase and α-amylase were ranked as TA ≈ PGG > TeGG > TGG > 1GG, and their inhibitory activities increases with the increase in the number of GMs. Moreover, the hypoglycemic effects of 1,2,3,4,6-pentagalloylglucose (PGG) and tannic acid (TA) in vitro and in vivo were also confirmed to be equivalent to or even stronger than that of acarbose. CONCLUSION: α-Glucosidase inhibitory activities in vitro and in vivo of GTs were positively correlated with the number of GTs, and the more the number, the stronger the activity. However, PGG with five GTs and TA with ten GTs showed almost identical α-glucosidase inhibitory activities, possibly due to the reduced binding force with the enzyme caused by spatial hindrance.

Identification of a common ice nucleus on hydrophilic and hydrophobic close-packed metal surfaces.

Establishing a general model of heterogeneous ice nucleation has long been challenging because of the surface water structures found on different substrates. Identifying common water clusters, regardless of the underlying substrate, is one of the key steps toward solving this problem. Here, we demonstrate the presence of a common water cluster found on both hydrophilic Pt(111) and hydrophobic Cu(111) surfaces using scanning tunneling microscopy and non-contact atomic force microscopy. Water molecules self-assemble into a structure with a central flat-lying hexagon and three fused pentagonal rings, forming a cluster consisting of 15 individual water molecules. This cluster serves as a critical nucleus during ice nucleation on both surfaces: ice growth beyond this cluster bifurcates to form two-dimensional (three-dimensional) layers on hydrophilic (hydrophobic) surfaces. Our results reveal the inherent similarity and distinction at the initial stage of ice growth on hydrophilic and hydrophobic close-packed metal surfaces; thus, these observations provide initial evidence toward a general model for water-substrate interaction.

Exogenous Spermidine Alleviates Diabetic Myocardial Fibrosis Via Suppressing Inflammation and Pyroptosis in db/db Mice

Background: The main pathological feature of diabetic cardiomyopathy (DCM) caused by diabetes mellitus is myocardial fibrosis. According to recent studies in cardiology, it has been suggested that spermidine (SPD) has cardioprotective properties. Aims: To explore the role and mechanism of SPD in alleviating myocardial fibrosis of DCM. Study Design: In vivo and in vitro study. Methods: Type 2 diabetic mice and primary neonatal mouse cardiac fibroblasts (CFs) were selected. Measurements of serum-related markers, echocardiographic analysis, and immunohistochemistry were used to evaluate myocardial fibrosis injury and the effects of SPD. The proliferation and migration of CFs undergoing different treatments were studied. Immunoblotting and real-time quantitative reverse transcription polymerase chain reaction were used to demonstrate molecular mechanisms. Results: In vivo immunoblotting analysis indicated a downregulation of ornithine decarboxylase and an upregulation of SPD/spermine N1-acetyltransferase. We observed cardiac dysfunction in diabetic mice after 12 weeks. However, the administration of exogenous SPD improved cardiac function, decreased collagen deposition, and reduced myocardial tissue damage. mRNA expression levels of NLRP3, Caspase-1, GSDMD-N, interleukin (IL)-1ß, IL-17A, and IL-18 were increased and suppressed in the myocardium of db/db mice upon treatment with SPD. SPD inhibited the proliferation, migration, and collagen secretion of high-glucose-treated fibroblasts in vitro. SPD inhibits the activation of the TGF-ß1/Smad signaling pathway and decreases collagen deposition by reducing pyroptosis and Smad-7 ubiquitination levels. Conclusion: Based on our findings, SPD may have potential applications in protecting against the deterioration of cardiac function in patients with DCM due to a significant new mechanism for diabetic myocardial fibrosis that we discovered.

Serum metabolomics profiling of improved metabolic syndrome is characterized by decreased pro-inflammatory biomarkers: A longitudinal study in Chinese male adults.

Metabolic syndrome (MetS) is a serious global health concern. The objective of this study is to dynamically investigate the changes of metabolic profiles and metabolites in Chinese male MetS subjects after an 18 months diet and exercise intervention. Fifty male MetS patients defined according to International Diabetes Federation 2005 guidelines were subjected to diet and exercise counseling for 18 months. Serum samples were taken at baseline, 12 months, and 18 months, respectively, for clinical evaluation and metabolomics analyses. Diet and exercise intervention for 18 months achieved significant improvements in the metabolic profiles of all participants. Nineteen subjects (38.0%) exhibited MetS remission at the end of the study. A total of 812 relative features were characterized and 61 were successfully identified. Furthermore, 17 differential metabolites were of significance at both time points (baseline-12 months, baseline-18 months) and presented nonlinear trends through time. Eight metabolites (47.1%) were predominantly converged to inflammation and oxidative stress. Pro-inflammatory biomarkers were remarkably decreased after 18 months of intervention, and prostaglandin E2, neuroprotectin D1, and taxiphyllin in combination were firstly found to demonstrate a fair discriminative power (area under curve = 0.911) to predict the improvement of MetS undergone diet and exercise intervention. The significant shift of metabolomic profiling after 18 months of lifestyle counseling provide a novel insight and reveal that earlier inflammation control may be of potential benefit in MetS management.

Exogenous spermidine alleviates diabetic cardiomyopathy via suppressing reactive oxygen species, endoplasmic reticulum stress, and Pannexin-1-mediated ferroptosis.

Diabetic cardiomyopathy (DCM) is a serious complication and death cause of diabetes mellitus (DM). Recent cardiology studies suggest that spermidine (SPD) has cardioprotective effects. Here, we verified the hypothesis of SPD's protective effects on DCM. Therefore, db/db mice and primary neonatal mouse cardiomyocytes were used to observe the effects of SPD. 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 SPD 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 to activate ERK1/2 signaling pathway in cardiomyocytes and activated NCOA4-mediated ferroptinophagy to promote lipid peroxidation and ferroptosis. Interestingly, SPD could reverse these molecular processes. Our findings indicate an important new mechanism for DCM and suggest that SPD has potential applicability to protect against deterioration of cardiac function with DCM.

UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment.

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis. Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms. Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism. Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.

Decoupled ultrafast electronic and structural phase transitions in photoexcited monoclinic VO2.

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 (M1-) to rutile (R-) VO2 and its association with electronic insulator-metal transitions (IMTs). Here, we illustrate the underlying atomistic processes and decoupling nature of photoinduced SPT and IMT in nonequilibrium states. The photoinduced SPT proceeds in the order of dilation of V-V pairs and increase of twisting angles after a small delay of ~40 fs. Dynamic simulations with hybrid functionals confirm the existence of isostructural IMT. The photoinduced SPT and IMT exhibit the same thresholds of electronic excitations, indicating similar fluence thresholds in experiments. The IMT is quasi-instantaneously (<10 fs) generated, while the SPT takes place with time a constant of 100 to 300 fs. These findings clarify some key controversies in the literature and provide insights into nonequilibrium phase transitions in correlated materials.

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.

Proteomic and metabolomic analyses reveal the novel targets of spermine for alleviating diabetic cardiomyopathy in type II diabetic mice.

Diabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes. Recent cardiology studies suggest that spermine has a cardioprotective effect. Here, we used proteomic and metabolomic analyses to reveal the underlying research targets in a type II diabetic (T2D) mouse model treated with spermine. Left ventricular tissues from nine mice (Control group, three; T2D group, three; T2D+SP group, three) were excised and analyzed. Quantitative analysis of the global proteome and metabolome was performed using the 4D label-free technique and untargeted metabolomics, respectively, and differentially expressed proteins (DEPs) and metabolites were used to perform bioinformatic analyses. A total of 169 DEPs were identified in T2D/Control group, including 115 upregulated and 54 downregulated proteins. Furthermore, 16 DEPs were identified in T2D+SP/T2D group, where these DEPs were found highly enriched in the cellular, metabolic processes, biological regulation, response to stimulus, and immune system process. The results of association analysis between proteomics and metabolomics showed that SP could affect the production of 51 metabolites by regulating the expression of 16 DEPs in the T2D+SP/T2D group. We also found that PRKG1 was closely related to the expressions of 10 overlapping metabolites between db/db and SP-treated mice. Our findings provide insights into the underlying mechanisms for DCM and suggest the potential applicability of utilizing spermine on protecting against DCM-associated cardiac function deterioration.

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.