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The pronounced exciton binding energy (Eb) in covalent organic frameworks (COFs) results in significant energy loss, thereby constraining the photocatalytic efficiency of COFs. Herein, triphenylamine is employed as an electron donor, while triphenyltriazine served as an acceptor; benzene, naphthalene, and anthracene are utilized as π‐bridges with progressively increasing conjugation to synthesize a series of D‐π‐A structured COFs photocatalysts (COF‐1, COF‐2, and COF‐3). The correlation between π‐bridge structures and Eb is systematically examined through the removal of hexavalent uranium U(VI) from tailings wastewater under visible light irradiation as a model reaction. Notably, an increase in π‐bridge conjugation initially enhanced and then diminished the photocatalytic properties of these three catalysts. This phenomenon can be attributed to the fact that coplanarity within the COFs frameworks does not consistently improve with greater π‐bridge conjugations; specifically, COF‐2 featuring a naphthalene π‐bridge exhibited the smallest dihedral angle. The reduced dihedral angle facilitated a more planar and delocalized electron transport pathway between donor and acceptor moieties, leading to decreased Eb and inhibited exciton recombination. Consequently, COF‐2 demonstrated exceptional photocatalytic reduction of U(VI), achieving efficiencies 1.8 times and 1.5 times greater than those of COF‐1 and COF‐3, respectively. This approach offers novel insights into mitigating Eb in COFs‐based photocatalysts. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) is a new well‐structured emerging technology with communication of smart devices using the 5G technology, infrastructures of roads, vehicles, smart cities, traffic systems and user applications. The IoT applications facilitate providing prompt emergency responses, and improved quality of vehicles, and road services, with cost‐effective activities in the intelligent transportation systems. Federated Learning (FL) enhances privacy and security in intelligent transportation systems and the Internet of Vehicles (IoV), using advanced prediction methods. Integrating blockchain with IoT, particularly in FL for transportation systems and IoV, bolsters security and data integrity. This approach keeps data local while only sharing model updates, enhancing privacy. Blockchain's transparency aids in efficient IoT collaboration, crucial for accountability. Its consensus algorithms further ensure network integrity, validating transactions and updates across devices, protecting against attacks, and fostering a transparent, collaborative environment. This comprehensive review paper delves into the innovative integration of blockchain technology with federated learning and the dynamic domain of IoV. It extensively analyzes the primary concepts, methodologies, and challenges associated with the deployment of FL in IoVs. This review presents a novel categorization examining three main types of blockchain‐based FL approaches vertical, horizontal, and decentralized each tailored to specific IoV communication scenarios like Vehicle‐to‐Vehicle (V2V), Vehicle‐to‐Infrastructure (V2I), and Vehicle‐to‐Cloud (V2C). It highlights FL applications in cyber‐attack detection, data sharing, traffic prediction, and privacy, considering Quality of Service factors. Finally, some main challenges and new open issues are discussed and assessed for federated machine learning approaches in the IoV. [ABSTRACT FROM AUTHOR]

Climate data collected through Internet of Things (IoT) devices often contain high‐dimensional, nonlinear, and auto‐correlated characteristics, and general causality analysis methods obtain quantitative causality analysis results between variables based on conditional independence tests or Granger causality, and so forth. However, it is difficult to capture dynamic properties between variables of temporal distribution, which can obtain information that cannot be obtained by the mean detection method. Therefore, this paper proposed a new causality analysis method based on Peter‐Clark (PC) algorithm and modified local Granger causality (MLGC) analysis method, called PC‐MLGC, to reveal the causal relationships between variables and explore the dynamic properties on temporal distribution. First, the PC algorithm is applied to compute the relevant variables of each variable. Then, the results obtained in the previous stage are fed into the modified local Granger causality analysis model to explore causalities between variables. Finally, combined with the quantitative causality analysis results, the dynamic characteristic curves between variables can be obtained, and the accuracy of the causal relationship between variables can be further verified. The effectiveness of the proposed method is further demonstrated by comparing it with standard Granger causality analysis and a two‐stage causal network learning method on one benchmark dataset and two real‐world datasets. [ABSTRACT FROM AUTHOR]

Background: AGEs accumulate in the skin as a result of a high‐sugar diet and play an important role in the skin aging process. Objectives: The aim of this study was to characterize the mechanism underlying the effect of a high‐sugar diet on skin aging damage at a holistic level. Methods: We established a high‐sugar diet mouse model to compare and analyze differences in physiological indexes. The effect of a high‐sugar diet on skin aging damage was analyzed by means of a transcriptome study and staining of pathological sections. Furthermore, the differences in the protein expression of AGEs and ECM components between the HSD and control groups were further verified by immunohistochemistry. Results: The skin in the HSD group mice tended toward a red, yellow, dark, and deep color. In addition, the epidermis was irregular with anomalous phenomena, the epidermis was thinned, and the dermis lost its normal structure and showed vacuolated changes. Transcriptomics results revealed significant downregulation of the ECM–receptor interaction pathway, significant upregulation of the expression of AGEs and significant downregulation of the expression levels of COLI, FN1, LM5, and TNC, among others ECM proteins and ECM receptors. Conclusions: High‐sugar diets cause skin aging damage by inducing the accumulation of AGEs, disrupting the expression of ECM proteins and their receptors, and downregulating the ECM–receptor interaction pathway, which affects cellular behavioral functions such as cell proliferation, migration, and adhesion, as well as normal skin tissue structure. [ABSTRACT FROM AUTHOR]

Stress‐induced hair loss is a prevalent health concern, with mechanisms that remain unclear, and effective treatment options are not yet available. In this study, we investigated whether stress‐induced hair loss was related to an imbalanced immune microenvironment. Screening the skin‐infiltrated immune cells in a stressed mouse model, we discovered a significant increase in macrophages upon stress induction. Clearance of macrophages rescues mice from stress‐induced hair shedding and depletion of hair follicle stem cells (HFSCs) in the skin, demonstrating the role of macrophages in triggering hair loss in response to stress. Further flow cytometry analysis revealed a significant increase in M1 phenotype macrophages in mice under stressed conditions. In searching for humoral factors mediating stress‐induced macrophage polarization, we found that the hormone Norepinephrine (NE) was elevated in the blood of stressed mice. In addition, in‐vivo and in‐vitro studies confirm that NE can induce macrophage polarization toward M1 through the β‐adrenergic receptor, Adrb2. Transcriptome, enzyme‐linked immunosorbent assay (ELISA), and western blot analyses reveal that the NLRP3/caspase‐1 inflammasome signaling and its downstream effector interleukin 18 (IL‐18) and interleukin 1 beta (IL‐1β) were significantly upregulated in the NE‐treated macrophages. However, inhibition of the NE receptor Adrb2 with ICI118551 reversed the upregulation of NLRP3/caspase‐1, IL‐18, and IL‐1β. Indeed, IL‐18 and IL‐1β treatments lead to apoptosis of HFSCs. More importantly, blocking IL‐18 and IL‐1β signals reversed HFSCs depletion in skin organoid models and attenuated stress‐induced hair shedding in mice. Taken together, this study demonstrates the role of the neural (stress)‐endocrine (NE)‐immune (M1 macrophages) axis in stress‐induced hair shedding and suggestes that IL‐18 or IL‐1β may be promising therapeutic targets. [ABSTRACT FROM AUTHOR]

With outstanding advantages of chemical synthesis, structural diversity, and mechanical flexibility, molecular ferroelectrics have attracted increasing attention, demonstrating themselves as promising candidates for next‐generation wearable electronics and flexible devices in the film form. However, it remains a challenge to grow high‐quality thin films of molecular ferroelectrics. To address the above issue, a volume‐confined method is utilized to achieve ultrasmooth single‐crystal molecular ferroelectric thin films at the sub‐centimeter scale, with the thickness controlled in the range of 100–1000 nm. More importantly, the preparation method is applicable to most molecular ferroelectrics and has no dependency on substrates, showing excellent reproducibility and universality. To demonstrate the application potential, two‐dimensional (2D) transitional metal dichalcogenide semiconductor/molecular ferroelectric heterostructures are prepared and investigated by optical spectroscopic method, proving the possibility of integrating molecular ferroelectrics with 2D layered materials. These results may unlock the potential for preparing and developing high‐performance devices based on molecular ferroelectric thin films. [ABSTRACT FROM AUTHOR]

To explore the role of PDE4D in diabetic nephropathy (DN) and investigate whether resveratrol protects against DN via inhibiting PDE4D. Diabetic db/db mouse and glomerular mesangial cell line (GMCs) were used to investigate the role of PDE4D and the protective effect of resveratrol on renal fibrosis under high glucose (HG) environment. Resveratrol alleviated the progress of DN via inhibiting mitochondrial fragmentation and restoring the expression of PDE4D, PKA, phosphorylated Drp1‐Ser637 and Drp1 in kidney of db/db mice. In HG‐exposed GMCs, resveratrol treatment decreased the expression of PDE4D, increased PKA level, and inhibited Drp1‐mediated mitochondrial fission. In contrast, PDE4D over‐expression blunted the inhibitory effects of resveratrol on Drp1 expression and mitochondrial fission. Moreover, PKA inhibitor H89 blunted the effects of resveratrol on phosphorylated Drp1‐Ser637 expression and mitochondrial fission in HG‐treated GMCs. Inhibition of mitochondrial fission with Drp1 inhibitor Mdivi‐1 alleviated mitochondrial dysfunction in GMCs under HG. These findings indicate PDE4D plays an important role in the process of DN. Resveratrol attenuates the development of DN by preventing mitochondrial fission through inhibiting PDE4D, which regulates the expression of phosphorylated Drp1‐Ser637 directly. [ABSTRACT FROM AUTHOR]

Background: For decades, video game‐related behaviors have been investigated in different psychologic research, much of whose attention has been paid to video game addiction (VGA), while the differences between VGA and social media addiction (SMA) should have deserved more attention. In addition to detecting common risk factors of VGA, one core question is whether social inclination (individualism or collectivism) matters. Object: The objectives of this study were to clarify the prevalence of VGA and SMA,, identify the influencing factors of VGA, and clarify the relationships between VGA and adolescents' individualism–collectivism inclination. Method: The survey was conducted among 110 adolescent psychiatric patients. For each interviewee, psychological scales were filled face to face. Path analysis was used to examine the causation structure of the childhood trauma‐related symptoms. Result: The prevalence of VGA was 40.9% (45 out of 110), and it was 41.8% for SMA (46 out of 110); childhood trauma, social media addiction, the individualistic inclination, and the rate of homosexuality were observed to be independent indicators for video game addiction (r2 = 0.46). Conclusion: Psychological counseling on patients' internet‐related behaviors may focus on the individualistic personality and possible childhood trauma, which are two important risk factors of video game addiction. It is recommended to distinguish between video game addiction and social addiction in clinical practice. [ABSTRACT FROM AUTHOR]

The breakthrough of energy storage technology will enable energy distribution and adaptation across space‐time, which is revolutionary for the generation of energy. Optimizing the energy storage performance of polymer dielectrics remains challenging via the physical process of electrical breakdown in solid dielectrics is hard to be intuitively obtained. In this review article, the application of computational simulation technologies is summarized in energy‐storage polymer dielectrics and the effect of control variables and design structures on the material properties with an emphasis on dielectric breakdown and energy storage performance are highlighted. The prediction and evaluation of material properties by combining various data analysis methods are reviewed. Finally, the outlook and challenges are discussed based on their current developments. This article covers not only an overview of the state‐of‐the‐art advances of breakdown modeling in energy‐storage polymer dielectrics but also the prospects that provide a new knob to synthesize high energy‐storage polymer dielectrics via computational simulation and a new research paradigm. [ABSTRACT FROM AUTHOR]

Aim: The functions of the interlaminar astrocytes in layer I of the human cortex are currently unknown. Here, we aimed to explore whether there is any morphological remodelling of interlaminar astrocytes in layer I of the temporal cortex in epilepsy. Methods: Tissues were obtained from 17 epilepsy surgery patients and 17 post‐mortem age‐matched controls. In addition, 10 Alzheimer's disease (AD) patients and 10 age‐matched controls were used as the disease control group. Paraffin sections (6 μm) and frozen sections (35 or 150 μm) of inferior temporal gyrus tissue were used for immunohistochemistry. With the use of tissue transparency, 3D reconstruction and hierarchical clustering, we performed a quantitative morphological analysis of astrocytes. Results: Upper and lower zones were identified in layer I of the human cortex. Compared with the astrocytes in layers IV–V, layer I interlaminar astrocytes occupied a significantly smaller volume and exhibited shorter and fewer process intersections. Increased Chaslin's gliosis (consisting of types I and II subpial interlaminar astrocytes) and number of glial fibrillary acidic protein (GFAP)‐immunoreactive interlaminar astrocytes in layer I of the temporal cortex were confirmed in patients with epilepsy. There was no difference in the number of interlaminar astrocytes in layer I between AD and age‐matched control groups. Using tissue transparency and 3D reconstruction technology, the astrocyte domain in the human temporal cortex was classified into four clusters, among which the interlaminar astrocytes in cluster II were more abundant in epilepsy, showing specific topological structures in patients with epilepsy. Furthermore, there was a significant increase in the astrocyte domain of interlaminar cells in layer I of the temporal cortex in patients with epilepsy. Conclusion: The observed significant astrocytic structural remodelling in the temporal cortex of epilepsy patients showed that the astrocyte domain in layer I may play an important role in temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Since the initial discovery of quantum teleportation, it is devoted to transferring unknown quantum states from one party to another distant partner. However, in the scenarios of remote sensing, what people truly care about is the information carried by certain parameters. The problem of multiparameter estimation in the framework of qutrit teleportation under amplitude damping (AD) noise is studied. Particularly, two schemes are proposed to battle against AD noise and enhance the precision of multiparameter estimation by utilizing weak measurement (WM) and environment‐assisted measurement (EAM). For two‐phase parameters encoded in a qutrit state, the analytical formulas of the quantum Fisher information matrix can be obtained. The results prove that the scheme of EAM outperforms the WM one in the improvements of both independent and simultaneous estimation precision. Remarkably, the EAM scheme can completely ensure the estimation precision against the contamination by AD noise. The reason should be attributed to the fact that EAM is carried out after the AD noise. Thus, it extracts information from both the system and the environment. The findings show that the techniques of WM and EAM are helpful for remote quantum sensing and can be generalized to other qutrit‐based quantum information tasks under AD decoherence. [ABSTRACT FROM AUTHOR]

Codonopsis radix was commonly used as food materials or herbal medicines in many countries. However, the comprehensive analysis of chemical constituents, and in vivo xenobiotics of Codonopsis radix remain unclear. In the present study, an integrated strategy with feature‐based molecular networking using ultra‐high‐performance liquid chromatography coupled with mass spectrometry was established to systematically screen the chemical constituents and the in vivo xenobiotics of Codonopsis radix. A step‐by‐step manner based on a composition database, visual structure classification, discriminant ions, and metabolite software prediction was proposed to overcome the complexities due to the similar structure of chemical constituents and metabolites of Codonopsis radix. As a result, 103 compounds were tentatively characterized, 20 of which were identified by reference standards. Besides, a total of 50 xenobiotics were detected in vivo, including 26 prototypes and 24 metabolites, while the metabolic features of the pyrrolidine alkaloids were elucidated for the first time. The metabolism reactions of pyrrolidine alkaloids and sesquiterpene lactones included oxidation, methylation, hydration, hydrogenation, demethylation, glucuronidation, and sulfation. This study provided a generally applicable approach to the comprehensive investigation of the chemical and metabolic profile of traditional Chinese medicine and offered reasonable guidelines for further screening of quality control indicators and pharmacodynamics mechanism of Codonopsis radix. [ABSTRACT FROM AUTHOR]

Postretrieval extinction procedures are effective nonpharmacological interventions for disrupting drug-associated memories. Nonetheless, the conditioned stimulus (CS) memory retrieval-extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval-extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1 hour before the extinction sessions decreased the heroin-priming-induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28 days of withdrawal (ie, remote heroin-associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval-extinction procedure on heroin-priming-induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval-extinction procedure resembled the inhibitory effect of UCS retrieval-extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval-extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin-associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug-associated memories. [ABSTRACT FROM AUTHOR]

Objectives: There are significant clinical challenges associated with alopecia treatment, including poor efficiency of related drugs and insufficient hair follicles (HFs) for transplantation. Skin‐derived precursors (SKPs) exhibit great potential as stem cell‐based therapies for hair regeneration; however, the proliferation and hair‐inducing capacity of SKPs gradually decrease during culturing. Materials and Methods: We describe a 3D co‐culture system accompanied by kyoto encyclopaedia of genes and genomes and gene ontology enrichment analyses to determine the key factors and pathways that enhance SKP stemness and verified using alkaline phosphatase assays, Ki‐67 staining, HF reconstitution, Western blot and immunofluorescence staining. The upregulated genes were confirmed utilizing corresponding recombinant protein or small‐interfering RNA silencing in vitro, as well as the evaluation of telogen‐to‐anagen transition and HF reconstitution in vivo. Results: The 3D co‐culture system revealed that epidermal stem cells and adipose‐derived stem cells enhanced SKP proliferation and HF regeneration capacity by amphiregulin (AREG), with the promoted stemness allowing SKPs to gain an earlier telogen‐to‐anagen transition and high‐efficiency HF reconstitution. By contrast, inhibitors of the phosphoinositide 3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) pathways downstream of AREG signalling resulted in diametrically opposite activities. Conclusions: By exploiting a 3D co‐culture model, we determined that AREG promoted SKP stemness by enhancing both proliferation and hair‐inducing capacity through the PI3K and MAPK pathways. These findings suggest AREG therapy as a potentially promising approach for treating alopecia. [ABSTRACT FROM AUTHOR]

Background and Aims. Magnifying chromoendoscopy (ME-CE) through the observation of pit patterns is a productive way to distinguish between neoplastic and nonneoplastic polyps. Magnifying optical enhancement technology (ME-OE) is an emerging virtual chromoendoscopy imaging technology and appeared to be a promising approach. However, this information is currently not available. This study is aimed at comparing the differential diagnostic value of ME-CE and OE for neoplastic and nonneoplastic polyps. Patients and Methods. Consecutive patients undergoing colonoscopy were randomized (1 : 1) into examination by ME-OE or ME-CE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of two endoscopy methods were compared using ME-OE (were classified according to the JNET classification) and ME-CE (were classified according to the Kudo pit pattern classification), respectively, and the time to predict the histological polyp type was compared. And the agreements between the pathological and clinical diagnosis by ME-OE or ME-CE were analyzed. Results. A total of 365 polyps were found in the 220 patients included (ME-OE: 185; ME-CE: 180.202 had nonneoplastic polyps, 163 had neoplastic polyps). The diagnostic accuracy of ME-OE was higher than that of ME-CE (93% vs. 92%, p > 0.05). The average diagnosis time was lower in ME-OE than ME-CE (83 ± 26.4 s vs. 194 ± 17.7 s , p < 0.001). The agreements between the pathological and clinical diagnosis were at least substantial in both groups. Conclusion. ME-OE was superlative to ME-CE in predicting the histology of polyps. OE devoted classification would possibly similarly enhance the endoscopist performance. The trial is registered with ChiCT2000032075. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) and non‐TIPS therapy (endoscopy and/or nonselective beta‐blockers [NSBB]) in patients with cirrhosis and active variceal hemorrhage who did not respond to high‐dose vasoactive drugs and required balloon tamponade for hemostasis. Methods: Medical records of cirrhotic patients who did not respond to high‐dose vasoactive drugs and required balloon tamponade for hemostasis at five university hospitals in China between January 2011 and December 2018 were reviewed. Treatment outcomes were compared between the TIPS and the non‐TIPS groups. Results: Treatment failure of variceal hemorrhage within 5 days was reported in six patients of the non‐TIPS group (N = 70) and none of the TIPS group (N = 66) (P =.028). The TIPS group had a higher 1‐year variceal rebleeding‐free rate compared with the non‐TIPS group (95.5% vs 60.0%, P <.001). One patient treated with TIPS and nine with non‐TIPS therapy experienced rebleeding within 5 days and 6 weeks after the intervention (P =.009). The cumulative 1‐year survival rate was higher in the TIPS group than in the non‐TIPS group (93.9% vs 78.6%, P =.01). The TIPS group had a higher incidence of hepatic encephalopathy within one year compared with the non‐TIPS group (18.2% vs 4.3%, P =.026). Conclusion: For patients with cirrhosis and active variceal bleeding who do not respond to high‐dose vasoactive agents and require a balloon tamponade for hemostasis, TIPS may be an appropriate treatment choice. [ABSTRACT FROM AUTHOR]

The effect of genistein (GEN) on the gene expression level of stromal cell‐derived factor‐1/CXCL‐12 and early growth response gene‐1 was studied in ovarian tissue of young and initially ageing (early stages in the ageing process) female rats. Forty, young female Sprague Dawley (SD) rats of 2–3 months old (200 ±20 g) and forty, initially ageing female SD rats of 10–12 months (490 ± 20 g) old were selected. According to the weight, rats were divided into control group, low‐dose group (L), medium‐dose group (M) and a high‐dose group (H) and were given 15, 30 and 60 mg/kg GEN respectively. The positive control (Oestrogen) group was given 0.5 mg/kg diethylstilbestrol. The treatment lasted for 30 days. The mRNA expression of C‐X‐C motif chemokine ligand 12 (CXCL‐12) and early growth response factor‐1 (EGR‐1) was measured by real‐time PCR, and protein expression of EGR‐1 was detected by Western blot. When compared to the negative control group (NC), the ovary/body weight ratio in the young rats decreased in the GEN group, but the difference was not significant. Similarly, compared with NC, the ovary/body weight ratio in the initially ageing rats also decreased with the increase in GEN concentration, but the decrease was significant in M and H groups (p <.01). The administration of GEN enhanced both the gene and protein expression levels of CXCL‐12 and EGR‐1 in the ovary. Pearson's correlation analysis showed a synergistic effect between CXCL‐12 and EGR‐1. Thus, we conclude that the effect of GEN on CXCL‐12 and EGR‐1 in the initially ageing group was obvious than that in the younger group. [ABSTRACT FROM AUTHOR]

Salt‐inducible kinase 2 (SIK2) is an important regulator in various intracellular signaling pathways related to apoptosis, tumorigenesis and metastasis. However, the involvement of SIK2 in gastric tumorigenesis and the functional linkage with gastric cancer (GC) progression remain to be defined. Here, we report that SIK2 was significantly downregulated in human GC tissues, and reduced SIK2 expression was associated with poor prognosis of patients. Overexpression of SIK2 suppressed the migration and invasion of GC cells, whereas knockdown of SIK2 enhanced cell migratory and invasive capability as well as metastatic potential. These changes in the malignant phenotype resulted from the ability of SIK2 to suppress epithelial–mesenchymal transition via inhibition of AKT/GSK3β/β‐catenin signaling. The inhibitory effect of SIK2 on AKT/GSK3β/β‐catenin signaling was mediated primarily through inactivation of AKT, due to its enhanced dephosphorylation by the upregulated protein phosphatases PHLPP2 and PP2A. The upregulation of PHLPP2 and PP2A was attributable to SIK2 phosphorylation and activation of mTORC1, which inhibited autophagic degradation of these two phosphatases. These results suggest that SIK2 acts as a tumor suppressor in GC and may serve as a novel prognostic biomarker and therapeutic target for this tumor. [ABSTRACT FROM AUTHOR]

This study explores the cost of security regulations in China, where firms are required to meet a certain profitability benchmark before applying for permission to raise more equity via secondary equity offerings (SEOs). Using a difference‐in‐differences setting, we show that firms affected by the regulation (i.e., firms with high external financing demands (EFD) but profitability lower than the regulatory requirement) significantly underperform their counterparts, while unaffected firms do not. The affected firms' performance decline increases (decreases) when the requirement of profitability is more (less) restricted. Consistently, the three‐day cumulative abnormal return (CAR) of firms with high EFD is significantly negative (positive) when the regulation is tightened (loosened). Our study provides evidence on how the cost of regulation affects companies that have growth opportunities. [ABSTRACT FROM AUTHOR]

To reconstruct the ceRNA biological network of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and to select an appropriate mRNA as a biomarker that could be used for CESC early diagnosis and prognosis evaluation. We downloaded CESC data from the TCGA public database, and statistical analysis was conducted with the R software to find out differential expressed genes encoding for lncRNAs, miRNAs, and mRNAs. The differentially expressed mRNAs (DEmRNAs) screened in the ceRNA network were analyzed for survival to find the mRNAs with significantly linked to the survival prognosis. These mRNAs were searched in the Pathological Atlas to identify the final appropriate mRNAs. Differential expression analysis revealed 773 lncRNAs, 94 miRNAs, and 2466 mRNAs. Survival analysis of DEmRNAs in the ceRNA network indicated that ADGRF4, ANXA8L1, HCAR3, IRF6, and PDE2A (P < 0.05) were negatively correlated with survival time. Verification of these six DEmRNAs in the Pathology Atlas indicated that PDE2A was a possible biomarker for CESC patients. PDE2A might be a biomarker for early diagnosis and prognosis evaluation of CESC patients, but due to the lack of available data, further studies may be needed for confirmation. [ABSTRACT FROM AUTHOR]

In order to investigate the mechanism of genistein (Gen) in the treatment of climacteric syndrome, an in vivo study was performed to investigate the beneficial effects of genistein on the expression of P450 aromatase (P450 arom) and follicle‐stimulating hormone receptor (FSHR) in the mouse ovary and uterus. Fifty female ICR mice (45 ± 5g, n = 50), aged 12 months, were divided into the following five groups with 10 animals in each: blank control group (CG), low‐dose genistein group (L‐Gen), middle‐dose genistein group (M‐Gen) and high‐dose genistein group (H‐Gen) (received 15, 30 and 60 mg/kg of genistein, respectively), and oestrogen group (EG; received 0.5 mg/kg diethylstilbestrol). The expression levels of the FSHR protein were determined by an immunohistochemical staining method. The expression of P450 arom, Cytochrome P450 19 (CYP19) and FSHR was quantified by real‐time PCR. Immunohistochemical results showed that the expression levels of the FSHR protein in the M‐Gen (average stained area: 20.79) and the H‐Gen (average stained area: 21.21) groups were significantly stronger than in the CG (average area was 17.24) group (p <.05). The expression levels of CYP19 mRNA and P450 arom were positively correlated with the dose of genistein. Specifically, the relative expression levels in the H‐Gen and EG groups were more than 1.5 times higher than in the CG group (p <.05). Genistein played a significant role in regulating aromatase and FSHR gene expression to improve perimenopausal ovarian and uterine function. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the effects of genistein (GEN) on expression of insulin‐like growth factor 1 (IGF‐1) and insulin‐like growth factor binding protein 1 (IGFBP‐1) in young and aged rat ovary. Forty young female Sprague Dawley (SD) rats (200 ± 20 g) and forty aged female SD rats (490 ± 20 g) were selected and according to weight, they were divided into the following five groups with eight animals in each: negative control group (NC), low‐dose group (L), middle‐dose group (M), high‐dose group (H) and positive control group (PC). GEN group received GEN of 15, 30, 60 mg/kg respectively. It lasted 30 days. Concentrations of serum hormones, IGF‐1 and IGFBP‐1 were determined by enzyme‐linked immunosorbent assay (ELISA). Gene and protein expressions of IGF‐1 and IGFBP‐1 were determined by real‐time PCR and Western blot respectively. Compared with NC, GEN significantly increased oestradiol‐17β(E2) level in aged rat, reduced luteinizing hormone (LH) level in young and aged rat. Serum levels of IGFBP‐1 in young rats were significantly higher in GEN groups (p < 0.05). mRNA and protein expression levels of IGF‐1 and IGFBP‐1 were positively correlated with GEN dose. GEN could significantly reduce the ratio of IGF‐1/IGFBP‐1 of aged rats. Multivariate Cox regression analysis result showed IGF‐1 and IGFBP‐1 levels significantly correlated with GEN dose. We speculate that there is an association between the addition of GEN and expression of IGF‐1 and IGFBP‐1, and the relationship between them is different in young and aged rat. [ABSTRACT FROM AUTHOR]

A top‐gate self‐aligned a‐IGZO TFT backplate with white OLED and color filter was demonstrated in this paper. Three kind of PV (passivation) hole etching sequences noted as case 1~3, were studied to verify the contact between ITO and Source/Drain electrode. For case 3, PV hole etching process after PLN patterning shows smooth metal surface and excellent panel performance. In contrast, Sourse and Drain metal corrosion occurred due to non‐uniform PV film deposition in other two cases , resulting in bad contact between ITO and S/D metal and poor panel performance. [ABSTRACT FROM AUTHOR]

Obesity is considered a chronic inflammatory disease, the inflammatory factors, such as interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and small inducible cytokine A5 (RANTES), are elevated in obese individuals. Pituitary adenylate cyclase‐activating polypeptide (PACAP) suppresses anti‐inflammatory cytokines and ameliorates glucose and lipid metabolism. Our previous study showed that Fas apoptosis inhibitory molecule (FAIM) is a new mediator of Akt2 signalling, increases the insulin signalling pathway and lipid metabolism. In this study, we found that PACAP promoted the expression of FAIM protein in a human hepatocyte cell line (L02). Overexpression of FAIM with lentivirus suppressed the expression of the inflammatory factor interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and tumour necrosis factor alpha (TNF‐α). Following treatment of obese mice with FAIM or PACAP for 2 weeks, inflammation was alleviated and the bodyweight and blood glucose levels were decreased. Overexpression of FAIM down‐regulated the expression of adipogenesis proteins, including SREBP1, SCD1, FAS, SREBP2 and HMGCR, and up‐regulated glycogen synthesis proteins, including Akt2 (Ser474) phosphorylation, GLUT2 and GSK‐3β, in the liver of obese mice. However, down‐regulation of FAIM with shRNA promotes obesity. Altogether, our data identified that FAIM mediates the function of PACAP in anti‐inflammation, glucose regulation and lipid metabolism in obese liver. [ABSTRACT FROM AUTHOR]

Background. Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet β cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of β cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in β-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods. Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3′-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. Results. miR-29a overexpression inhibited proliferation (P<0.01) and GSIS under high-glucose stimulation (P<0.01). Cdc42 overexpression promoted proliferation (P<0.05) and GSIS under high-glucose stimulation (P<0.05). miR-29a overexpression decreased Cdc42 expression (P<0.01), whereas miR-29a downregulation increased Cdc42 expression (P<0.01). The results showed that the Cdc42 mRNA 3′-UTR is a direct target of miR-29a in vitro. Additionally, Cdc42 reversed miR-29a-mediated inhibition of proliferation and GSIS (P<0.01). Furthermore, miR-29a inhibited β-catenin expression (P<0.01), whereas Cdc42 promoted β-catenin expression (P<0.01). Conclusion. By negatively regulating Cdc42 and the downstream molecule β-catenin, miR-29a inhibits MIN6 proliferation and insulin secretion. [ABSTRACT FROM AUTHOR]

Metal halide perovskite single crystals are emerging candidates for X‐ray detection, however, it is challenging for growth of thickness‐controlled single‐crystal wafer on commercial backplanes, limiting their practical imaging application. Herein, integration of micrometer‐thick methylammonium lead triiodide (MAPbI3) single‐crystal wafer on indium tin oxide (ITO) substrates by methylamine (MA)‐induced interface recrystallization is reported. Through selection of hole transport material with rich functional group, intimate interface contact with low trap density can be achieved, leading to superior carrier transport properties and homogeneous photoresponse. The as‐fabricated X‐ray detectors exhibit high sensitivity of 1.4 × 104 µC Gyair−1 cm−2 and low detection limit of 177 nGyair s−1, which are comparable to previous reports based on free‐standing MAPbI3 bulk crystals. This work provides a feasible strategy for constructing substrate‐integrated single‐crystal perovskite wafers with controlled thickness, which may promote practical imaging application of perovskite X‐ray detectors. [ABSTRACT FROM AUTHOR]

Objectives: Temporomandibular joint osteoarthritis (TMJOA) is approximately twice as prevalent in women than in men. Synoviocytes are believed to play a critical role in joint inflammation. However, it is unknown whether synoviocytes from different genders possess sexual dimorphisms that contribute to female‐predominant TMJOA. Materials and Methods: Freund's complete adjuvant combined with monosodium iodoacetate was used to induce TMJOA in female and male rats. Histologic and radiographic features were used to evaluate TMJOA. The expression of CD68, MCP‐1, iNOS, and IL‐1β was detected by immunohistochemistry and real‐time PCR. Primary fibroblast‐like synoviocytes (FLSs) isolated from the synovial membrane of female and male rats were used for in vitro experiments. Results: Female rats showed aggravated TMJOA features as compared to male rats. Increased expression of iNOS and IL‐1β was detected in synovial membrane from female TMJOA rats as compared to male rats. Furthermore, greater amounts of CD68‐positive macrophage infiltration and increased MCP‐1 expression around the synovial membrane were detected in female TMJOA rats compared to males. Primary cultured FLSs from female rats showed higher sensitivity to TNF‐α treatment and recruited increased macrophage migration than male FLSs. More important, ovariectomy (OVX) by ablation in female rats repressed the sensitivity of female FLSs to TNF‐α treatment due to the loss of estrogen production. Blockage of the estrogen receptor repressed estrogen‐potentiated TNF‐α‐induced pro‐inflammatory cytokine expression in OVX‐FLSs. Moreover, the injection of estrogen receptor antagonists relieved the cartilage destruction and bone deterioration of TMJOA in female rats. Conclusion: Estrogen‐sensitized synoviocytes in female rats may contribute to gender differences in the incidence and progression of TMJOA. [ABSTRACT FROM AUTHOR]

Abstract: Erasable electrical conductive domain walls in an insulating ferroelectric matrix provide novel functionalities for applications in logic and memory devices. The crux of such success requires sufficiently high wall currents to drive high‐speed and high‐power nanodevices. This work provides an appealing strategy to increase the current by two orders of magnitude through the careful selection of current flowing paths along the charged walls. The dense walls come into form through the hierarchical evolution of the 71°, 109°, and 180° domains of epitaxial BiFeO3 films in a planar‐geometry ferroelectric resistance‐switching memory cell. The engineered films grown on SrTiO3 and GdScO3 substrates allow the observation of detailed local configurations and the evolution of the different domain types using vector piezo‐force microscopy. The higher local electrical conductivity near the charged domain walls is identified by conductive atomic‐force microscopy. It is shown that 180° domain reversal proceeds by three‐step 71° rotations of the pristine domains. Surprisingly, a maximum current of ≈300 nA is observed for current paths along charge‐uncompensated head‐to‐head hierarchical domain walls connecting the two electrodes on the film surface. Furthermore, the achievable current level can be conveniently controlled by varying the relative directions of the initial polarization and the applied field. [ABSTRACT FROM AUTHOR]

In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26-composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of 'death signal', thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid peroxide-mediated stress signaling pathways. The work presents the ability of Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that maintenance or increase of Cx26-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency. Picture: The survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed) and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density condition. [ABSTRACT FROM AUTHOR]

The bromodomain ( BRD) and extra-terminal domain ( BET) protein family bind to acetylated histones on lysine residues and act as epigenetic readers. Recently, the role of this protein family in bone loss has been gaining attention. Earlier studies have reported that benzotriazepine (Bzt) derivatives could be effective inhibitors of BET proteins. In this study, using in silico tools we designed three Bzt analogs (W49, W51, and W52). By docking, molecular simulations, and chemiluminescent Alpha Screen binding assay, we show that the studied analogs were selective at inhibiting BRD4 when compared to BRD2. Furthermore, we tested the effectiveness of these analogs on osteoclast formation and function. Among the examined analogs, Bzt-W49 and Bzt-W52 were found to be the most potent inhibitors of osteoclastogenesis without cytotoxicity in murine RAW264.7 osteoclast progenitors. Both the compounds also inhibited osteoclast formation without affecting cell viability in human CD14+ monocytes. Moreover, owing to attenuated osteoclastogenesis, actin ring formation and bone resorptive function of osteoclasts were severely perturbed. In conclusion, these results suggest that the novel BRD4-selective Bzt analogs designed in this study could be explored further for developing therapeutics against bone loss diseases characterized by excessive osteoclast activity. [ABSTRACT FROM AUTHOR]

Hydrophilic interaction chromatography (HILIC) is an emerging separation mode of liquid chromatography (LC). Using highly hydrophilic stationary phases capable of retaining polar/ionic metabolites, and accompany with high organic content mobile phase that offer readily compatibility with mass spectrometry (MS) has made HILIC an attractive complementary tool to the widely used reverse-phase (RP) chromatographic separations in metabolomic studies. The combination of HILIC and RPLC coupled with an MS detector expands the number of detected analytes and provides more comprehensive metabolite coverage than use of only RP chromatography. This review describes the recent applications of HILIC-MS/MS in metabolomic studies, ranging from amino acids, lipids, nucleotides, organic acids, pharmaceuticals, and metabolites of specific nature. The biological systems investigated include microbials, cultured cell line, plants, herbal medicine, urine, and serum as well as tissues from animals and humans. Owing to its unique capability to measure more-polar biomolecules, the HILIC separation technique would no doubt enhance the comprehensiveness of metabolite detection, and add significant value for metabolomic investigations. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:574-600, 2016 [ABSTRACT FROM AUTHOR]

A time-domain method for calculating the band structure of one-dimensional periodic structures is proposed. During the time-stepping of the method, the column vector containing the spatially sampled field data is updated by multiplying with an iteration matrix. The iteration matrix is first obtained by using the matrix-exponential decomposition technique. Then, the small nonzero elements of the matrix are pruned to improve its sparse structure, so that the efficiency of the matrix-vector multiplication involved in each time-step is enhanced. The numerical results show that the method is conditionally stable but is much more stable than the conventional finite-difference time-domain (FDTD) method. The time-step with which the method runs stably can be much larger than the Courant-Friedrichs-Lewy (CFL) limit. And moreover, the method is found to be particularly efficient for the band structure calculation of large-scale structures containing a defect with a very high wave speed, where the conventional FDTD method may generally lose its efficiency severely. For this kind of structures, not only the stability requirement can be significantly relaxed, but also the matrix-pruning operation can be very effectively performed. In the numerical experiments for large-scale quasi-periodic phononic crystal structures containing a defect layer, significantly higher efficiency than the conventional FDTD method can be achieved by the proposed method without an evident accuracy deterioration if the wave speed of the defect layer is relatively high. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Shortening time from biopsy to graft preparation is crucial for the coverage of extensive burn wound in major burn patients. This study was aimed to shorten the culture time of keratinocytes by means of one modified cell culture method. Three factors (temperature of dispase, area of skin, and age of patient) that might have impacts on cell behavior were evaluated. The results showed that cells isolated with dispase at 37°C exhibited an improved cell activity than being isolated at 4°C. The time that cells reached subconfluence with various skin areas was in order of 3 cm2 < 2 cm2 < 1 cm2 (120.07 ± 5.03 h, 141.33 ± 4.16 h, and 193.33 ± 6.11 h, respectively). Furthermore, compared with the young and middle-aged groups, proliferation of keratinocytes isolated from children skin tissue was better. These results indicated that 3 cm2 skin biopsy from a young patient, isolated with dispase at 37°C, was a promising strategy to shorten the cultivation of keratinocytes. [ABSTRACT FROM AUTHOR]

The separation and determination of proteins in food is an important aspect in food industry. Inspired by the self-polymerization of dopamine under alkaline conditions and the natural adhesive properties of polydopamine, in this paper, a simple and economical method was developed for the preparation of polydopamine-coated open tubular column, in which ammonium persulfate was used as the source of oxygen to induce and facilitate the polymerization of dopamine to form polydopamine. In comparison with a naked fused-silica capillary, the direction and magnitude of the electro-osmotic flow of the as-prepared polydopamine-coated open tubular column could be manipulated by varying the pH values of background solutions due to the existence of amine and phenolic hydroxyl groups on polydopamine coating. The surface morphology of the polydopamine-coated open tubular column was studied by scanning electron microscopy, and the thickness of polydopamine coating was 106 nm. The performance of the polydopamine-coated open tubular column was validated by analysis of proteins. The relative standard deviations of migration times of proteins representing run-to-run, day-to-day, and column-to-column were less than 3.5%. In addition, the feasibility of the polydopamine-coated open tubular column for real samples was verified by the separation of proteins in chicken egg white and pure milk. [ABSTRACT FROM AUTHOR]

Tuning the lattice degree of freedom in nanoscale functional crystals is critical to exploit the emerging functionalities such as piezoelectricity, shape-memory effect, or piezomagnetism, which are attributed to the intrinsic lattice-polar or lattice-spin coupling. Here it is reported that a mechanical probe can be a dynamic tool to switch the ferroic orders at the nanoscale multiferroic phase boundaries in BiFeO3 with a phase mixture, where the material can be reversibly transformed between the 'soft' tetragonal-like and the 'hard' rhombohedral-like structures. The microscopic origin of the nonvolatile mechanical switching of the multiferroic phase boundaries, coupled with a reversible 180° rotation of the in-plane ferroelectric polarization, is the nanoscale pressure-induced elastic deformation and reconstruction of the spontaneous strain gradient across the multiferroic phase boundaries. The reversible control of the room-temperature multiple ferroic orders using a pure mechanical stimulus may bring us a new pathway to achieve the potential energy conversion and sensing applications. [ABSTRACT FROM AUTHOR]

The alcohol dehydrogenase promoter PadhE and mixed acid fermentation pathway deficient mutants of Escherichia coli were employed to produce poly(3-hydroxybutyrate) (P3HB) under microaerobic condition. The E. coli mutant with ackA-pta, poxB, ldhA, and adhE deletions accumulated 0.67 g/L P3HB, up to 78.84% of cell dry weight in tube cultivation. The deletion of pyruvate formate-lyase gene pflB drastically decreased P3HB production and P3HB content to 0.09 g/L and 24.44%, respectively. Overexpressing pflB via the plasmid in its knocked out mutant restored cell growth and P3HB accumulation, indicating the importance of the pyruvate formate-lyase in microaerobic carbon metabolism. The engineered E. coli BWapld (pWYC09) produced 5.00 g/L P3HB from 16.50 g/L glucose in 24 h batch fermentation, and P3HB production yield from glucose was 0.30 g/g, which reached up to 63% of maximal theoretical yield. [ABSTRACT FROM AUTHOR]

A new kind of pregnane-type alkaloid, 20α-dimethylamino-3β-senecioylamino-16β-hydroxy-pregn-5-ene (K-6), was isolated from Pachysandra terminalis Sieb. et Zucc., and its antibacterial activity against MRSA and MRSE was evaluated. We found that K-6 showed antibacterial effects against MRSA and MRSE with minimum inhibitory concentration values (25 mg/L), but did not induce antibiotic resistance in bacteria easily. The administration of K-6 dose-dependently improved the animal survival rate of mice infected with MRSA, with survival rates of 36.34% and 66.67% in the low-dose and high-dose groups, respectively. The protective effects were associated with the reduction of the bacterial titers in the blood and with the morphological amelioration of infected tissues. Scanning and transmission electron microscopy analyses indicated that the cytoplasm shrink of bacterial cells led to noticeable gaps between the cell membrane and cell cytoplasm, and the severely damaged cell membrane resulted in leakage of intracellular content, which ultimately caused the lethal effect of K-6 on bacteria. These findings demonstrated that K-6 is a potential agent against MRSA and MRSE. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A rapid and useful approach for screening potential bioactive components in Ginkgo biloba extract (GBE) with preventive effect against diabetic nephropathy (DN) was developed using mesangial cells extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Mesangial cells were first divided into two groups according to their treatments with high glucose or high glucose plus GBE. After incubation for 4, 8, 12, 16, 24 and 48 h, the cells were harvested and extracted with 40% acetic acid in water before LC-MS/MS analysis. Then, 19 compounds and five metabolites were found to selectively combine with mesangial cells. Notably, compounds including quercetin and rutin were identified or tentatively characterized according to the results of retention time and MS spectra, which is highly consistent with our previous reports that quercetin and rutin are potent protective agents against glomerulosclerosis in DN. Therefore, all these results indicate that target cell extraction coupled with LC-MS/MS analysis can be successfully applied for predicting the bioactive components in GBE with preventive effect against DN. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Repaglinide is a short-acting insulin secretagogue, which often results in considerable interindividual variability in therapeutic efficacy when widely used in a clinical setting. Among various reasons under discussion is genetic polymorphism, especially the genes related to insulin secretion and resistance. Recent studies have described the importance of PPARD in regulating the secretion and resistance of insulin. However, little is known about the impacts of PPARD genetic polymorphism on the efficacy of repaglinide. Therefore, the current study was designed to investigate the associations of PPARD rs2016520 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. A total of 338 T2DM patients and 200 healthy subjects were genotyped for PPARD rs2016520 polymorphism by polymerase chain reaction-restriction fragment length polymorphism assay. A total of 84 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take repaglinide for 8 weeks. Then the pharmacodynamic parameters of repaglinide and biochemical indicators were determined before and after repaglinide treatment. No significant difference was found in either allelic frequency ( P = 0.298) or genotype distribution ( P = 0.151) of PPARD rs2016520 between T2DM patients and healthy subjects. However, T2DM patients carrying genotype TC showed a significantly lower increase in postprandial serum insulin (mU/L) than those with wild-type TT ( P < 0.05). These findings suggest that PPARD rs2016520 polymorphism might influence the therapeutic effect of repaglinide rather than T2DM susceptibility in Chinese Han T2DM patients. [ABSTRACT FROM AUTHOR]

A simple, easy and economical approach for the preparation of a hybrid carbon/silica monolithic capillary column was described for the first time by using silica monolith as framework in combination with hydrothermal carbonization at 180°C. During the preparation process, formamide was introduced to the reaction solutions to reduce the dissolution rate of monolithic silica skeleton and its optimal concentration was 1.5 M. Fourier transform infrared spectrometry, scanning electron microscopy, energy dispersive X-ray spectrometry, and inverse size exclusion chromatography were carried out to characterize the as-prepared column. The results demonstrated that carbon spheres ranging from 150 to 1000 nm were successfully attached to the surface of silica skeleton. The prepared hybrid carbon/silica column had a permeability of 4.4 × 10−14 m2. Chromatographic performance of the column was evaluated by separation of various compounds including alkylbenzenes, nucleosides and bases, and aromatic acids. The column exhibited an efficiency of 75 000 plates/m for butylbenzene at the optimal linear velocity of 0.23 mm/s. The successful separation of these compounds and the study on mechanism indicated that the column can be applied in mixed-mode chromatography. [ABSTRACT FROM AUTHOR]

Study Objective To investigate the associations of NOS1 AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2 DM) and repaglinide therapeutic efficacy in Chinese patients with T2 DM. Design Prospective case-control study. Setting Academic medical center. Patients A total of 300 patients with T2 DM and 200 healthy volunteers were enrolled to identify NOS1 AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks. Measurements and Main Results Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c, fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS ( mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers. Conclusion The NOS1 AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2 DM patients. [ABSTRACT FROM AUTHOR]

Aims Stroke causes both brain inflammation and immunodepression. Mild-to-moderate hypothermia is known to attenuate brain inflammation, but its role in stroke-induced immunodepression ( SIID) of the peripheral immune system remains unknown. This study investigated the effects in rats of moderate intra-ischemic hypothermia on SIID and brain inflammation. Methods Stroke was induced in rats by permanent distal middle cerebral artery occlusion combined with transient bilateral common carotid artery occlusion, while body temperature was reduced to 30°C. Real-time PCR, flow cytometry, in vitro T-cell proliferation assays, in vivo delayed-type hypersensitivity (DTH) reaction and confocal microscopy were used to study SIID and brain inflammation. Results Brief intra-ischemic hypothermia helped maintain certain leukocytes in the peripheral blood and spleen and enhanced T-cell proliferation in vitro and delayed-type hypersensitivity in vivo, suggesting that hypothermia reduces SIID. In contrast, in the brain, brief intra-Ischemic hypothermia inhibited m RNA expression of anti-inflammatory cytokine IL-10 and proinflammatory mediators INF-γ, TNF-α, IL-2, IL-1β and MIP-2. Brief intra-Ischemic hypothermia also attenuated the infiltration of lymphocytes, neutrophils ( MPO+ cells) and macrophages ( CD68+ cells) into the ischemic brain, suggesting that hypothermia inhibited brain inflammation. Conclusions Brief intra-ischemic hypothermia attenuated SIID and protected against acute brain inflammation. [ABSTRACT FROM AUTHOR]