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Background: The optimal treatment for some symptomatic, benign osteopathy lesions is yet to be identified. Purpose: To investigate the clinical efficiency of cementoplasty in managing symptomatic, benign osteopathy. Material and Methods: Between June 2006 and January 2020, we retrospectively enrolled 31 patients (10 men, 21 women; mean age = 46.5 ± 16.6 years; age range = 20–85 years), accounting for 34 treatment sites, who underwent percutaneous osteoplasty (14 treatment sites) and percutaneous vertebroplasty (20 treatment sites) with digital subtraction angiography (DSA) or DSA combined with computed tomography (CT). All the participants experienced different degrees of clinical symptoms with benign osteopathy lesions. The technical success of the procedure and occurrence of complications were recorded. Follow-up examinations were conducted to assess the treatment outcome using the MacNab criteria. Results: All the participants had a diagnosis of benign osteopathy lesions before or after the cementoplasty. Surgery was successfully completed in all patients. Cement distributions were diffuse and homogeneous, with the complication of cement leakage occurring in 17.6% (6 of 34) of the lesions. The leakage occurred in the intervertebral disc (n = 1), the intra-articular space (n = 1), and the surrounding soft tissue (n = 4). Analysis of the treatment outcome using the MacNab criteria revealed that all patients showed improvement in their clinical symptoms to some extent and in the quality of life. Conclusion: Cementoplasty is an effective treatment for symptomatic, benign osteopathy, with the advantage of favorable clinical outcomes, and low complication rate. [ABSTRACT FROM AUTHOR]

The multiconfiguration Dirac–Hartree–Fock (MCDHF) method is employed to calculate excitation energies, transition rates, lifetimes and Land e ́ g factors for the lowest 700 levels belonging to the 22 configurations 3 s 2 3 p { 3 l , 4 l ′ } , 3 s 3 p 2 { 3 l , 4 l ′ } , 3 s 2 3 d { 3 d , 4 s , 4 p } , 3 s { 3 p 3 d 2 , 3 d 3 } , 3 p { 3 p 3 , 3 p 2 3 d , 3 p 3 d 2 , 3 d 3 } , 3 d 4 with l = 1, 2 and l ′ = 0, 1, 2, 3 in Kr XXIII. The present excitation energies are compared with available experimental and theoretical values. The mean relative difference between our results and the values provided by the National Institute of Standards and Technology (NIST) is only 0.05%, which suggests a good agreement. The uncertainties of the transition rates are estimated based on quantitative and qualitative evaluation method which analyzes the dependencies of the line strength S on the gauge parameter G. It is observed that 49.6% of E1 S values have uncertainties of ≤ 1% (AA) and over 82% have uncertainties of ≤ 3% (A). The present wavelengths and transition rates are compared with the experimental values and generally good agreements have been achieved. For lifetime, the present MCDHF values fall well within the range of experimental error. Comparison of the computed Land e ́ g factors is also made with the Land e ́ g factors in pure L S -coupling. These accurate data can be useful for fusion plasma research and astrophysical applications. • Energies, transition data and landé g factors for lowest 700 levels are provided. • The MCDHF method is used to perform the calculations. • The most accurate and complete atomic data of Si-like Kr XXIII are provided. [ABSTRACT FROM AUTHOR]

• Patients with AKI occurrence were more likely than those without AKI to have higher serum hepcidin and uNGAL levels. • Higher levels of serum hepcidin and uNGAL are each independent predictor of sepsis-induced AKI. • Serum hepcidin predicts the development of AKI similarly to uNGAL in septic patients. • Hepcidin adds significant accuracy to AKI prediction in combination with uNGAL alone. The early prediction of the development of acute kidney injury (AKI) in critically ill patients with sepsis would facilitate early effective intervention. Recently, interest has focused on the biomarkers for AKI-linked iron metabolism. This study aimed to assess the early predictive values of hepcidin, neutrophil gelatinase-associated lipocalin (NGAL), and their combination for secondary AKI in patients with sepsis. A prospective cohort study was performed in septic patients. Serum and urine hepcidin, and urine NGAL were analyzed at admission. The primary outcome measure was occurrence of sepsis-induced AKI based on 2011 Kidney Disease: Improving Global Outcomes (KDIGO) criteria during the first week of ICU stay. Of the 90 patients analyzed finally in the study, 44 (48.9%) patients developed AKI. Patients with AKI occurrence were more likely than those without AKI to have higher serum hepcidin and urine NGAL levels at admission (P < 0.01). Higher concentrations of these biomarkers were each independent predictor of the development of AKI in critically septic patients within the first week of their ICU stay. Serum hepcidin and urine NGAL (AUROC 0.787, 95% CI 0.688 to 0.8660 and AUROC 0.729, 95% CI 0.625 to 0.818, respectively) were comparable predictive indicators of AKI occurrence (P = 0.43 for DeLong's test). Combining both biomarkers increased the AUROC to 0.828(95% CI 0.733 to 0.899), and this performance was statistically significantly better than urine NGAL alone (P = 0.03 for DeLong's test). Serum hepcidin measured at admission predicts the development of AKI similarly to urine NGAL. However, serum hepcidin adds significant accuracy to this prediction in combination with urine NGAL alone and has a good predictive value in patients with sepsis. Larger studies are needed to validate and explain these findings. [ABSTRACT FROM AUTHOR]

Objective: To construct a MRI radiomics model and help radiologists to improve the assessments of pelvic lymph node metastasis (PLNM) in endometrial cancer (EC) preoperatively.Methods: During January 2014 and May 2019, 622 EC patients (age 56.6 ± 8.8 years; range 27-85 years) from five different centers (A to E) were divided into training set, validation set 1 (351 cases from center A), and validation set 2 (271 cases from centers B-E). The radiomics features were extracted basing on T2WI, DWI, ADC, and CE-T1WI images, and most related radiomics features were selected using the random forest classifier to build a radiomics model. The ROC curve was used to evaluate the performance of training set and validation sets, radiologists based on MRI findings alone, and with the aid of the radiomics model. The clinical decisive curve (CDC), net reclassification index (NRI), and total integrated discrimination index (IDI) were used to assess the clinical benefit of using the radiomics model.Results: The AUC values were 0.935 for the training set, 0.909 and 0.885 for validation sets 1 and 2, 0.623 and 0.643 for the radiologists 1 and 2 alone, and 0.814 and 0.842 for the radiomics-aided radiologists 1 and 2, respectively. The AUC, CDC, NRI, and IDI showed higher diagnostic performance and clinical net benefits for the radiomics-aided radiologists than for the radiologists alone.Conclusions: The MRI-based radiomics model could be used to assess the status of pelvic lymph node and help radiologists improve their performance in predicting PLNM in EC.Key Points: • A total of 358 radiomics features were extracted. The 37 most important features were selected using the random forest classifier. • The reclassification measures of discrimination confirmed that the radiomics-aided radiologists performed better than the radiologists alone, with an NRI of 1.26 and an IDI of 0.21 for radiologist 1 and an NRI of 1.37 and an IDI of 0.24 for radiologist 2. [ABSTRACT FROM AUTHOR]

The tin β-γ-liquid triple point and the melting curve at high pressure have been controversial for a long time. Apart from being of fundamental importance, the sound velocity at high pressure and high temperature also provides a practical approach for determining melting curves and phase boundaries. We investigated the sound velocities and phase diagram of tin up to 5GPa and 800K by ultrasonic measurements on a multi-anvil apparatus. The β-γ-liquid triple point obtained in this work is 3.02±0.05GPa and 562±2K. The experimental data and the extrapolated melting curve of the c phase using the Simon-type equation are in good agreement with the theoretical and most of the experimental results at high pressure. These results indicate that sound velocity measurements based on multi-anvil apparatus can be a convenient and reliable approach to determine the high-pressure melting curve and phase boundaries of materials. [ABSTRACT FROM AUTHOR]

Background: Disputes exist regarding whether the apparent diffusion coefficient (ADC) can differentiate the tumor grade, deep myometrial invasion and lymphovascular space invasion (LVSI) in endometrial cancer. The aim of this review was to assess the diagnostic performance of the ADC value in endometrial cancer. Material and Methods: The PubMed, Web of Science, Embase and Cochrane Library databases were searched for studies that used the ADC value to assess tumor grade, deep myometrial invasion and LVSI in endometrial cancer. We used forest plots to analyze the heterogeneity and generate the pooled sensitivity (SEN) and specificity (SPE). We used summary receiver operating characteristic (SROC) curves to work out the area under the SROC curve (AUC). Likelihood ratios (LRs) were also obtained. Results: Of the 460 identified studies, 11 studies met our inclusion criteria and were included. Overall, nine studies (491 patients) aimed at differentiating high tumor grade had a pooled SEN, SPE and AUC of 77%, 73% and 81%, respectively; three studies (181 patients) for differentiating deep myometrial invasion had a pooled SEN, SPE and AUC of 71%, 67% and 77%, respectively; and two studies (106 patients) for differentiating LVSI had a pooled SEN and SPE of 66% and 74%, respectively. The positive and negative LRs were 2.77 and 0.35 for the tumor grade, 2.08 and 0.45 for deep myometrial invasion, and 2.48 and 0.45 for LVSI. Conclusion: This meta-analysis showed that the ADC value had a moderate diagnostic performance for the tumor grade, deep myometrial invasion and LVSI in endometrial cancer. [ABSTRACT FROM AUTHOR]

Implied motion can enhance the consumer's judgment of food freshness. However, this enhancing effect has only been investigated for a few products. Furthermore, researchers have not conclusively determined whether the effects of the low-level visual sensory processing and high-level conceptual processing on food evaluation differ. In Experiment 1, using different fruits in static water (fruit_IS), fruit with implied moving water (fruit_IM), or only fruits as stimuli, we initially generalized the effect of implied motion on the broader category of fruit, and implied motion improved the perceived freshness of the fruit. In Experiment 2, we recorded event-related potentials (ERPs) and measured the temporal processes involved in the mechanism by which implied motion improved perceived fruit freshness. The behavioral results further supported the findings from Experiment 1. The ERP data revealed a pronounced positive difference between fruit_IM and fruit-only conditions recorded from posterior electrodes at approximately 200-300 ms (P2). This difference reflected the low-level visual implied motion sensory processing involved in the effect of implied motion on improving food freshness. Additionally, an early frontocentral negativity difference of approximately 300-500 ms between fruit_IM and fruit-only conditions was recorded, which reflected the high-level visual conceptual processing involved in the effect of implied motion on improving food freshness. These results strengthen and extend previous behavioral findings indicating that implied motion enhances the consumer's judgment of food freshness across various food categories, and improves our understanding of the cognitive processes involved in the mechanism by which implied motion influences food judgments. [ABSTRACT FROM AUTHOR]

Four new compounds, aneglycoside A-C (1-3) and timosaponin U (4), were isolated from the rhizomes of Anemarrhena asphodeloides. Their structures were determined through extensive spectroscopic analysis, chemical characteristics, and high-resolution mass spectrometry (HRMS). All the isolations were evaluated for cytotoxicity against HepG2, Hela, and SGC7901 human cancer lines. Compounds 1, 2, and 4 showed weak antiproliferative activities on HepG2, Hela, and SGC7901 cells. [ABSTRACT FROM AUTHOR]

The CMOS (Complementary Metal-Oxide-Semiconductor) is a new type of solid image sensor device widely used in object tracking, object recognition, intelligent navigation fields, and so on. However, images captured by outdoor CMOS sensor devices are usually affected by suspended atmospheric particles (such as haze), causing a reduction in image contrast, color distortion problems, and so on. In view of this, we propose a novel dehazing approach based on a local consistent Markov random field (MRF) framework. The neighboring clique in traditional MRF is extended to the non-neighboring clique, which is defined on local consistent blocks based on two clues, where both the atmospheric light and transmission map satisfy the character of local consistency. In this framework, our model can strengthen the restriction of the whole image while incorporating more sophisticated statistical priors, resulting in more expressive power of modeling, thus, solving inadequate detail recovery effectively and alleviating color distortion. Moreover, the local consistent MRF framework can obtain details while maintaining better results for dehazing, which effectively improves the image quality captured by the CMOS image sensor. Experimental results verified that the method proposed has the combined advantages of detail recovery and color preservation. [ABSTRACT FROM AUTHOR]

In this paper, we propose a sparse coding tracking algorithm based on the Cartesian product of two sub-codebooks. The original sparse coding problem is decomposed into two sub sparse coding problems. And the dimension of sparse representation is intensively enlarged at a lower computational cost. Furthermore, in order to reduce the number of L 1 -norm minimization, ridge regression is employed to exclude the substantive outlying particles according to the reconstruction error. Finally the high-dimension sparse representation is put into the classifier and the candidate with the maximal response is considered as the target. Both qualitative and quantitative evaluations on challenging benchmark image sequences demonstrate that the proposed tracking algorithm performs favorably against several state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) generate matrix, which in turn may also regulate HSCs function during liver fibrosis. We hypothesized that HSCs may endocytose matrix proteins to sense and respond to changes in microenvironment. Primary human HSCs, LX2, or mouse embryonic fibroblasts (MEFs) [wild-type; c-abl/; or Yes, Src, and Fyn knockout mice (YSF/)] were incubated with fluorescent-labeled collagen or gelatin. Fluorescence-activated cell sorting analysis and confocal microscopy were used for measuring cellular internalization of matrix proteins. Targeted PCR array and quantitative real-time PCR were used to evaluate gene expression changes. HSCs and LX2 cells endocytose collagens in a concentration- and time-dependent manner. Endocytosed collagen colocalized with Dextran 10K, a marker of macropinocytosis, and 5-ethylisopropyl amiloride, an inhibitor of macropinocytosis, reduced collagen internalization by 46%. Cytochalasin D and ML7 blocked collagen internalization by 47% and 45%, respectively, indicating that actin and myosin are critical for collagen endocytosis. Wortmannin and AKT inhibitor blocked collagen internalization by 70% and 89%, respectively, indicating that matrix macropinocytosis requires phosphoinositide-3-kinase (PI3K)/AKT signaling. Overexpression of dominant-negative dynamin-2 K44A blocked matrix internalization by 77%, indicating a role for dynamin- 2 in matrix macropinocytosis. Whereas c-abl/ MEF showed impaired matrix endocytosis, YSF/ MEF surprisingly showed increased matrix endocytosis. It was also associated with complex gene regulations that related with matrix dynamics, including increased matrix metalloproteinase 9 (MMP-9) mRNA levels and zymographic activity. HSCs endocytose matrix proteins through macropinocytosis that requires a signaling network composed of PI3K/AKT, dynamin- 2, and c-abl. Interaction with extracellular matrix regulates matrix dynamics through modulating multiple gene expressions including MMP-9. [ABSTRACT FROM AUTHOR]

Background Malaria remains a public health problem in the remote and poor area of Yunnan Province, China. Yunnan faces an increasing risk of imported malaria infections from Mekong river neighboring countries. This study aimed to identify the high risk area of malaria transmission in Yunnan Province, and to estimate the effects of climatic variability on the transmission of Plasmodium vivax and Plasmodium falciparum in the identified area. Methods We identified spatial clusters of malaria cases using spatial cluster analysis at a county level in Yunnan Province, 2005-2010, and estimated the weekly effects of climatic factors on P. vivax and P. falciparum based on a dataset of daily malaria cases and climatic variables. A distributed lag nonlinear model was used to estimate the impact of temperature, relative humidity and rainfall up to 10-week lags on both types of malaria parasite after adjusting for seasonal and long-term effects. Results The primary cluster area was identified along the China-Myanmar border in western Yunnan. A 1°C increase in minimum temperature was associated with a lag 4 to 9 weeks relative risk (RR), with the highest effect at lag 7 weeks for P. vivax (RR = 1.03; 95% CI, 1.01, 1.05) and 6 weeks for P. falciparum (RR = 1.07; 95% CI, 1.04, 1.11); a 10-mm increment in rainfall was associated with RRs of lags 2-4 weeks and 9-10 weeks, with the highest effect at 3 weeks for both P. vivax (RR = 1.03; 95% CI, 1.01, 1.04) and P. falciparum (RR = 1.04; 95% CI, 1.01, 1.06); and the RRs with a 10% rise in relative humidity were significant from lag 3 to 8 weeks with the highest RR of 1.24 (95% CI, 1.10, 1.41) for P. vivax at 5-week lag. Conclusions Our findings suggest that the China-Myanmar border is a high risk area for malaria transmission. Climatic factors appeared to be among major determinants of malaria transmission in this area. The estimated lag effects for the association between temperature and malaria are consistent with the life cycles of both mosquito vector and malaria parasite. These findings will be useful for malaria surveillance-response systems in the Mekong river region. [ABSTRACT FROM AUTHOR]

Background: Malaria is a significant threat to population health in the border areas of Yunnan Province, China. How to accurately measure malaria transmission is an important issue. This study aimed to examine the role of slide positivity rates (SPR) in malaria transmission in Mengla County, Yunnan Province, China. Methods: Data on annual malaria cases, SPR and socio-economic factors for the period of 1993 to 2008 were obtained from the Center for Disease Control and Prevention (CDC) and the Bureau of Statistics, Mengla, China. Multiple linear regression models were conducted to evaluate the relationship between socio-ecologic factors and malaria incidence. Results: The results show that SPR was significantly positively associated with the malaria incidence rates. The SPR (β = 1.244, p = 0.000) alone and combination (SPR, β = 1.326, p<0.001) with other predictors can explain about 85% and 95% of variation in malaria transmission, respectively. Every 1% increase in SPR corresponded to an increase of 1.76/100,000 in malaria incidence rates. Conclusion: SPR is a strong predictor of malaria transmission, and can be used to improve the planning and implementation of malaria elimination programmes in Mengla and other similar locations. SPR might also be a useful indicator of malaria early warning systems in China. [ABSTRACT FROM AUTHOR]

In this study, one new species and one new variety are described and illustrated. Elatostema intanondense Q. Lin (Urticaceae), collected from Doi Intanond of Chiang Mai in Thailand, is morphologically similar to E. subincisum Weddell, but differs by having obscure stipules (vs. conspicuous, linear-lanceolate, 5-6 mm long in E. subincisum), and elliptic to lanceolate nanophylls, 3-7 × 1.5-3.0 mm (vs. absent in E. subincisum). Elatostema ranongense Yahara var. glabroum Q. Lin, a new variety collected from Khasi Hills in Mawhplong of Meghalaya, India. This new variety has glabrous stems and glabrous leaves that differs from var. ranongense that having densely hirtellous stems, densely strigillose leaf blade on abaxial surface along veins. [ABSTRACT FROM AUTHOR]

It has been suggested that developmental dyslexia involves various literacy, sensory, motor skill, and processing speed deficits. Some recent studies have shown that individuals with developmental dyslexia exhibit implicit motor learning deficits, which may be related to cerebellar functioning. However, previous studies on implicit motor learning in developmental dyslexics have produced conflicting results. Findings from cerebellar lesion patients have shown that patients' implicit motor learning performance varied when different hands were used to complete tasks. This suggests that dyslexia may have different effects on implicit motor learning between the two hands if cerebellar dysfunction is involved. To specify this question, we used a one-handed version of a serial reaction time task to compare the performance of 27 Chinese children with developmental dyslexics with another 27 age-matched children without reading difficulties. All the subjects were students from two primary schools, Grades 4 to 6. The results showed that children with developmental dyslexic responded more slowly than nondyslexic children, and exhibited no implicit motor learning in the condition of left-hand response. In contrast, there was no significant difference in reaction time between two groups of children when they used the right hand to respond. This finding indicates that children with developmental dyslexia exhibited normal motor skill and implicit motor learning ability provided the right hand was used. Taken together, these results suggested that Chinese children with developmental dyslexia exhibit unilateral deficits in motor skill and implicit motor learning in the left hand. Our findings lend partial support to the cerebellar deficit theory of developmental dyslexia. [ABSTRACT FROM AUTHOR]

Impatiens pingxiangensis H. Y. Bi & S. X. Yu (Balsaminaceae), a new species from the limestone areas in Guangxi, China, is described and illustrated. The new species is similar to I. obesa in having succulent stems, subsessile peduncle, tufted pedicel and the lower petal in each pair of lateral united petals being connate, but differs from the latter by having perennial stems, leaf blades with 7-9 pairs of lateral veins, 1-2-flowered racemes, ovate inner lateral sepals, and elliptic capsule. Moreover, the pollen and seed coat characters also support the recognition of the new species. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major public health burden in the tropics with the potential to significantly increase in response to climate change. Analyses of data from the recent past can elucidate how short-term variations in weather factors affect malaria transmission. This study explored the impact of climate variability on the transmission of malaria in the tropical rain forest area of Mengla County, south-west China. Methods: Ecological time-series analysis was performed on data collected between 1971 and 1999. Auto-regressive integrated moving average (ARIMA) models were used to evaluate the relationship between weather factors and malaria incidence. Results: At the time scale of months, the predictors for malaria incidence included: minimum temperature, maximum temperature, and fog day frequency. The effect of minimum temperature on malaria incidence was greater in the cool months than in the hot months. The fog day frequency in October had a positive effect on malaria incidence in May of the following year. At the time scale of years, the annual fog day frequency was the only weather predictor of the annual incidence of malaria. Conclusion: Fog day frequency was for the first time found to be a predictor of malaria incidence in a rain forest area. The one-year delayed effect of fog on malaria transmission may involve providing water input and maintaining aquatic breeding sites for mosquitoes in vulnerable times when there is little rainfall in the 6-month dry seasons. These findings should be considered in the prediction of future patterns of malaria for similar tropical rain forest areas worldwide. [ABSTRACT FROM AUTHOR]

The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions. Although E2Fs have been widely studied in mammals, there have been few studies performed in insects. Here, we determined the function of E2F4 in the silkworm, Bombyx mori. We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals. Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase, whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase. These results indicate that BmE2F4 is important in cell cycle regulation. We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN‐SWU1 cells and DNA synthesis in the silk gland. Furthermore, we identified a protein called Bm14‐3‐3ζ that can interact with BmE2F4 and allow it to localize in the nucleus. Overexpression of the Bm14‐3‐3ζ gene led to cell cycle arrest in the G1 phase, while knocking down the gene increased the proportion of cells in S phase. These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation. [ABSTRACT FROM AUTHOR]

The article presents a study on the immobilization of UDP-galactose 4-epimerase from Escherichia coli on the yeast cell surface. UDP-galactose 4-epimerase from Escherichia coli catalyzes the reversible reaction between UDP-galactose and UDP-glucose. Enzyme activity analyses with EBY100 cells showed that the enzyme displayed on the yeast cell surface was very active in the conversion between UDP-Glc and UDP-Gal.

The actin cytoskeleton has long been implicated in protein secretion. We investigated whether Rho and Rac, known regulators of the cytoskeleton, are involved in amylase secretion by mouse pancreatic acini. Secretagogues, including cholecystokinin (CCK) and the acetylcholine analog carbachol, increased the amount of GTP-bound RhoA and Racl and induced translocation from cytosol to a membrane fraction. Immunocytochemistry revealed the translocation of Rho and Rac within the apical region of the cell. Expression by means of adenoviral vectors of dominant-negative Rho (RhoNl9), dominant-negative Rac (RacN17), and Clostridium Botulinum C3 exotoxin, which ADP ribosylates and inactivates Rho, significantly inhibited amylase secretion by CCK and carbachol; inhibiting both Rho and Rac resulted in a greater reduction. This inhibitory effect of RhoN19 on CCK-induced amylase secretion was apparent in both the early and late phases of secretion, whereas RacN17 was more potent on the late phase of secretion. None of these three affected the basal Ca2+ or the peak intracellular Ca2+ concentration stimulated by CCK. Latrunculin, a marine toxin that sequesters actin monomers, time-dependently decreased the total amount of filamentous actin (F-actin) and dose-dependently decreased secretion by secretagogues without affecting Ca2+ signaling. These data suggest that Rho and Rac are both involved in CCK-induced amylase release in pancreatic acinar cell possibly through an effect on the actin cytoskeleton. [ABSTRACT FROM AUTHOR]

Cholecystokinin (CCK) is a major regulator of pancreatic acinar cells and was shown previously to be capable of inducing cytoskeletal changes in these cells. In the present study, using NIH3T3 cells stably transfected with CCK-A receptors as a model cell, we demonstrate that CCK can induce actin stress fibers through a G[sub 13]- and RhoA-dependent mechanism. CCK induced stress fibers within minutes similar to those induced by lysophosphatidic acid (LPA), the active component of serum. The effects of CCK were mimicked by active RhoV14 and blocked by dominant-negative RhoN19, Clostridium botulinum C3 transferase, and the Rho-kinase inhibitor Y-27632. CCK rapidly induced active Rho in cells as shown with a pull-down assay using the Rho binding domain of rhotekin and by a serum response element (SRE)-luciferase reporter assay. To evaluate the G protein mediating the action of CCK, cells were transfected with active α-subunits; Gα[sub 13] and Gα[sub 12] but not Gα[sub q] induced stress fibers and in some cases cell rounding. A p115 Rho guanine nucleotide exchange factor (GEF) regulator of G protein signaling (RGS) domain known to interact with G[sub 12/13] inhibited active α[sub 12/13]and CCK-induced stress fibers, whereas RGS2 and RGS4, which are known to inhibit G[sub q], had no effect. Cotransfection with plasmids coding for the G protein α-subunit carboxy-terminal peptide from α[sub 13] and, to a lesser extent α[sub 12], also inhibited the effect of CCK, whereas the peptide from α[sub q] did not. These results show that in NIH3T3 cells bearing CCK-A receptors, CCK activates Rho primarily through G[sub 13], leading to rearrangement of the actin cytoskeleton. [ABSTRACT FROM AUTHOR]

Pancreatic secretion can be influenced by cholecystokinin (CCK) either directly via actions on acinar cells or indirectly via actions on nerves. The presence and functional roles of CCK receptors on human pancreatic acinar cells remains unclear. In the current study human pancreatic acini were isolated and then treated with CCK-8, gastrin and/or carbachol. Functional parameters were measured including intracellular [Ca2+] and amylase secretion. It was observed that human acini did not respond to CCK agonists but did respond to carbachol with robust increases in functional parameters. Adenoviral-mediated gene transfer of CCK1 or CCK2 receptors to the human cells resulted in cell responses to CCK agonists. In order to determine the reason for the lack of responsiveness of the human acini, expression of receptor mRNAs was determined using quantitative RT-PCR and localized by in situ hybridization, mRNA levels for CCK1 receptors were ∼30 times lower than those of CCK2 receptors, which were ∼10 times lower than those of m3 Ach receptors as measured by quantitative PCR. Neither CCK1 nor CCK2 receptors were localized in adult human pancreas by in situ hybridization. These results indicate that human pancreatic acinar cells do not respond directly to CCK receptor activation and this is likely due to an insufficient level of receptor expression. [ABSTRACT FROM AUTHOR]

Genetically engineered mouse models play a pivotal role in the modeling of diseases, exploration of gene functions, and the development of novel therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated genome editing technology has revolutionized the process of developing such models by enabling precise genome modifications of the multiple interested genes simultaneously. Following genome editing, an efficient genotyping methodology is crucial for subsequent characterization. However, current genotyping methods are laborious, timeconsuming, and costly. Here, using targeting the mouse trypsinogen genes as an example, we introduced common applications of CRISPR-Cas9 editing and a streamlined cost-effective genotyping workflow for CRISPR-edited mouse models, in which Sanger sequencing is required only at the initial steps. In the F0 mice, we focused on identifying the presence of positive editing by PCR followed by Sanger sequencing without the need to know the exact sequences, simplifying the initial screening. In the F1 mice, Sanger sequencing and algorithms decoding were used to identify the precise editing. Once the edited sequence was established, a simple and effective genotyping strategy was established to distinguish homozygous and heterozygous status by PCR from tail DNA. The genotyping workflow applies to deletions as small as one nucleotide, multiple-gene knockout, and knockin studies. This simplified, efficient, and cost-effective genotyping shall be instructive to new investigators who are unfamiliar with characterizing CRISPR-Cas9-edited mouse strains. [ABSTRACT FROM AUTHOR]

Circadian disorder such as light exposure at night are risk factors for NAFLD Prolactin (PRL), a pituitary derived hormone, is recently shown to improve fatty liver. Noteworthy, PRL is secreted in an oscillating pattern. We aimed to explore the role of PRL rhythm in hepatic lipid metabolism. Serum PRL levels in 8:00, 16:00, and 24:00 of subjects without or with NAFLD were evaluated. A cosine model was fitted to the curve of dynamic PRL levels. Luciferase report assay, ChIP and EMSA were used to examine the mechanism of PRL rhythm. Hight fat diet (HFD) C57BL/6 mice were categorized into HFD, HFD+jet-lag group for 16 weeks and serum PRL levels at ZT0, ZT4, ZT8, ZT12, ZT16, ZT20 were determined. Then mice in HFD+jet-lag group were randomly assigned to HFD+ jet lag and HFD+jet-lag+PRL for 14 days. Hepatic lipid content, clock genes and lipid metabolic genes in liver were detected. PRL in 8:00, 16:00 and 24:00 were all significantly lower in NAFLD group than in controls. Cosine curve analysis showed that NAFLD patients had reduced amplitude and delayed phase shift of PRL levels. After adjusted for confounders, light exposure at night is a risk factor for NAFLD, yet this association was dampened after adjusted for PRL rhythm. Luciferase report assay in 293T cell and EMSA assay in human pituitary tissue showed that Prl can be transactivated by core clock gene Rorα via RORα response element RORE. In mice, dynamic PRL attained highest levels at ZT12 in HFD mice but remained low in HFD+jet-lag mice. ChIP analysis showed that binding of Rorα and Prl promoter in HFD mouse pituitary at ZT12 was inhibited under HFD+jet-lag. Furthermore, hepatic lipid content was significantly higher in HFD+jet-lag group than that in HFD, and can be mitigated after 14 days PRL intervention at ZT12. We also found that PRL injection reversed changes of clock and lipid metabolic gene rhythm caused by jet-lag. PRL can serve as an endocrine sensor that transmits rhythmic signals from central nervous system to liver and thus regulating hepatic lipid metabolism. Disclosure: B. Yan: None. P. Zhang: None. D. Zhu: None. Funding: National Natural Science Foundation of China (81900787, 81770819) [ABSTRACT FROM AUTHOR]

Disturbance of innate and adaptive immune systems is responsible for β-cell destruction in type 1 diabetes (T1D). Although increasing evidence indicated a crucial role for B cells in disease pathogenesis, exactly how B-cell subsets contribute to T1D remains unclear. This study aimed to evaluate the potential role of B-cell subset in the development of T1D. We enrolled 56 people with T1D, including 8 people receiving mesenchymal stromal cell (MSC) treatment, 22 people with T2D, and 26 healthy controls. ELISPOT assay was used to assess the role of B-cell subset in activation of diabetogenic T cells. NOD mice and adoptive transfer assays were utilized to study the role of B-cell subset in T1D in vivo. Plasmablasts, but not naïve, unswitched or switched memory B cells, were increased in patients with recent-onset T1D, compared with those with long-term T1D, T2D and healthy controls. In patients with recent-onset T1D, plasmablast number negatively correlated with fasting C-peptide and area under the curve of C-peptide. Plasmablasts decreased in line with an improvement of residual β-cell function 3 months after MSC treatment. Compared with other B-cell subsets, plasmablasts expressed a high level of CD86, which negatively correlated with the residual β-cell function while positively correlated with the number of islet autoantibodies. ELISPOT assay further showed that plasmablasts isolated from participants with T1D induced a dramatic increase of interferon-γ secretion in GAD65 stimulated T cells. Compared with euglycemic NOD mice, the number of plasmablasts was increased in the spleen, pancreatic lymph nodes, and islets of diabetic NOD mice. Moreover, adoptive transfer of plasmablasts mixed with T cells from diabetic NOD mice into NOD/SCID mice accelerated the development of T1D. These data firstly demonstrated that plasmablasts play a vital role in immune disturbance, further expanding the knowledge of T1D pathogenesis. Plasmablasts may serve as a novel therapeutic target in T1D. Disclosure: B. Yan: None. Q. Ling: None. J. Lu: None. D. Zhu: None. [ABSTRACT FROM AUTHOR]

C14H9Cl2F3N4S, monoclinic, P21/c (no. 14), a = 11.6567(3) Å, b = 4.80480(10) Å, c = 28.1051(7) Å, β = 101.336(2)°, V = 1543.40(6) Å3, Z = 4, Rgt(F) = 0.0358, wRref(F2) = 0.1014, T = 250 K. [ABSTRACT FROM AUTHOR]

A metal-free method for synthesis of N-(2-hydroxyaryl)benzotriazoles via O-arylation of N-hydroxybenzotriazoles with readily available diaryliodonium salts and sequential N-O bond cleavage under mild conditions has been developed. The [3,3]-rearrangement of N-O bond cleavage could take place on the N instead of C atom. The reaction was compatible with diverse functional groups and a new type of P,N-ligand was synthesized in three steps. [ABSTRACT FROM AUTHOR]

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. [ABSTRACT FROM AUTHOR]

Cholesterol crystals participate in cholesterol nucleation; however, the role of cholesterol crystals in gallstone development is unknown. Mucin secretion contributes to increased size of gallstones. Cholesterol crystals activate inflammasomes and participate in many sterile inflammation related human diseases. We investigated the role of cholesterol crystals and mucins in sterile inflammation and gallstone enlargement. We found that expression of mucin 5AC (MUC5AC), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and interleukin-1b (IL-1b) was increased significantly in tissues adjacent to gallstones. Experiments in vitro showed that cholesterol crystals promote MUC5AC secretion; they also increase expression of NLRP3, NLR family CARD domain-containing 4 (NLRC4), apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and cleaved caspase-1 in biliary epithelial cells. Inhibition of Inflammasomes by NLRP3, ASC or caspase-1 small interfering RNAs reduced MUC5AC secretion. Also, the IL-1 receptor antagonist, IL1RA, and caspase-1 inhibitor, Ac-YVAD, both inhibited MUC5AC secretion induced by cholesterol crystals. We found that inflammasome activation participates in cholesterol crystal induced mucin secretion and gallstone development. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and challenging management. The present study aimed to investigate the expression of programmed death ligand-1 (PD-L1) and V-domain Ig-containing suppressor of T cell activation (VISTA) in ACC and their associations with clinicopathological features and survival outcomes. Immunohistochemistry was performed on formalin-fixed paraffin-embedded specimens from 54 ACC patients. Chi-square/Fisher's exact tests or independent samples t/Mann--Whitney U tests were performed to assess correlations between immunoscores and clinicopathological parameters. The Kaplan--Meier method and Cox regression were conducted for survival analysis and to identify independent predictors of overall (OS) and disease-free (DFS) survival. Results showed that VISTA was expressed in tumor cells (TCs) and tumor-infiltrating immune cells (TICs) in 81.5% (44/54) and 40.7% (22/54) of the patients, respectively. PD-L1 positivity was found in either TCs or TICs in 11.1% (6/54) of the patients. Patients with positive VI STA expression in TCs had a higher tumor stage (56.9% vs 20%, P = 0.036) and Ki-67 index (30.50 ± 23.51% vs 14.76 ± 11.75%, P = 0.006). However, PD-L1 positivity in either TCs or TICs had no association with patient clinicopathological features. A higher VISTA expression intensity, a larger area and a higher immunoscore were associated with increased risks of disease progression and overall mortality, but PD-L1 expression in TCs or TICs was not associated with OS or DFS. In conclusion, positive TC VISTA expression was correlated with pathological parameters related to malignancy in ACC patients. This finding provides novel evidence of the value of VISTA, in addition to PD-L1, as an immunotherapeutic target in ACC. [ABSTRACT FROM AUTHOR]

The visual magnocellular-dorsal (M-D) deficit theory of developmental dyslexia (DD) is still highly debated. Many researchers have made great efforts to investigate the relationship between M-D dysfunction and reading disability. Given that visual analysis plays an important role in Chinese reading, the present study tried to examine how the M-D dysfunction affected Chinese character recognition in Chinese children with DD. Sixteen DD children with M-D deficit, fifteen DD children with normal M-D function and twenty-seven age-matched typically developing children participated in this study. A global/local decision task was adopted, in which we manipulated the spatial frequency of target characters to separate an M-D condition from an unfiltered condition. Results of reaction times and error rates showed that in the M-D condition both M-D normal dyslexics and controls exhibited a significant global precedence effect, with faster responses and lower error rates in global decision than in local decision. In contrast, this global advantage was absent for the M-D impaired dyslexics. Accordingly, we propose that the M-D impairment present in some but not all dyslexics might influence global recognition of Chinese characters in this subgroup of children with DD, which might be implicated in their difficulties in learning to read. [ABSTRACT FROM AUTHOR]

Based on examination of specimens of Elatostema J. R. Forster & G. Forster (Urticaceae) from Vietnam, Elatostema albopilosum W.T. Wang var. vicinum L. D. Duan & Y. Lin, a new variety collected from Bac Can Province and Tuyen Quang Province, Vietnam, is described and photographed. This new variety has glabrous stems, glabrous leaves and glabrous peduncles which differs from var. albopilosum that having sparsely puberulent leaf blade on abaxial surface along veins and sparsely strigillose leaf blade on adaxial surface, and short pilose peduncles. E. integrifolium (D. Don) Wedd. and E. pseudodissectum W. T. Wang, two species previously known from Vietnamese adjacent countries, are newly recorded from Ninh Binh Province and Tam Dao National Park, Vietnam, respectively. The vouchers are kept in the Herbarium (PE) of Institute of Botany, Chinese Academy of Sciences, Beijing, China, and their descriptions and photographs are also provided. [ABSTRACT FROM AUTHOR]

Diamond is the hardest known material in nature and features a wide spectrum of industrial and scientific applications. The key to diamond's outstanding properties is its elasticity, which is associated with its exceptional hardness, shear strength, and incompressibility. Despite many theoretical works, direct measurements of elastic properties are limited to only ~1.4 kilobar (kb) pressure. Here, we report ultrasonic interferometry measurements of elasticity of void-free diamond powder in a multianvil press from 1 atmosphere up to 12.1 gigapascal (GPa). We obtained high-accuracy bulk modulus of diamond as K0 = 439.2(9) GPa, K0' = 3.6(1), and shear modulus as G0 = 533(3) GPa, G0' = 2.3(3), which are consistent with our first-principles simulation. In contrast to the previous experiment of isothermal equation of state, the K0' obtained in this work is evidently greater, indicating that the diamond is not fully described by the "n-m" Mie-Grüneisen model. The structural and elastic properties measured in this work may provide a robust primary pressure scale in extensive pressure ranges. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO) has multiple biological functions, including the modulation of glucose metabolism. However, the mechanisms underlying the action of EPO are still obscure. This study is aimed at investigating the potential mechanisms by which EPO improves glucose tolerance in an animal model of type 2 diabetes. Male C57BL/6 mice were fed with high-fat diet (HFD) for 12 weeks and then treated with EPO (HFD-EPO) or vehicle saline (HFD-Con) for two week. The levels of fasting blood glucose, serum insulin and glucose tolerance were measured and the relative levels of insulin-related phosphatidylinositol 3-kinase (PI3K)/Akt, insulin receptor (IR) and IR substrate 1 (IRS1) phosphorylation were determined. The levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6- phosphatase (G6Pase), toll like receptor 4 (TLR4), tumor necrosis factor (TNF)-α and IL-6 expression and nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK) and p38 MAPK activation in the liver were examined. EPO treatment significantly reduced the body weights and the levels of fasting blood glucose and serum insulin and improved the HFD-induced glucose intolerance in mice. EPO treatment significantly enhanced the levels of Akt, but not IR and IRS1, phosphorylation, accompanied by inhibiting the PEPCK and G6Pase expression in the liver. Furthermore, EPO treatment mitigated the HFD-induced inflammatory TNF-α and IL-6 production, TLR4 expression, NF-κB and JNK, but not ERK and p38 MAPK, phosphorylation in the liver. Therefore, our data indicated that EPO treatment improved glucose intolerance by inhibiting gluconeogenesis and inflammation in the livers of HFD-fed mice. [ABSTRACT FROM AUTHOR]

Orthographic neighborhood size (N size) effect in Chinese character naming has been studied in adults. In the present study, we aimed to explore the developmental characteristics of Chinese N size effect. One hundred and seventeen students (40 from the 3rd grade with mean age of 9 years; 40 from the 5th grade with mean age of 11 years; 37 from the 7th grade with mean age of 13 years) were recruited in the study. A naming task of Chinese characters was adopted to elucidate Nsize- effect development. Reaction times and error rates were recorded. Results showed that children in the 3rd grade named characters from large neighborhoods faster than named those from small neighborhoods, revealing a facilitatory N size effect; the 5th graders showed null N size effect; while the 7th graders showed an inhibitory N size effect, with longer reaction times for the characters from large neighborhoods than for those from small neighborhoods. The change from facilitation to inhibition of neighborhood size effect across grades suggested the transition from broadly tuned to finely tuned lexical representation in reading development, and the possible inhibition from higher frequency neighbors for higher graders. [ABSTRACT FROM AUTHOR]

We investigated the effects of apocynin on high-fat diet- (HFD-) induced insulin resistance in C57BL/6 mice. After 12 weeks of HFD, the mice that exhibited insulin resistance then received 5 weeks of apocynin (2.4 g/L, in water). Following apocynin treatment, fasting glucose, insulin, and glucose tolerance test showed significant improvement in insulin sensitivity in HFD-fed mice. We demonstrated that serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and leptin were remarkably reduced with apocynin treatment. We also found that mRNA expression of TNF-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in the liver and mRNA expression of TNF-α, IL-6, MCP-1, and leptin in adipose tissue were suppressed by apocynin. Furthermore, the activity of transcription factor NF-κB in the liver was significantly suppressed with apocynin treatment. These results suggest that apocynin may reduce inflammatory factors in the blood, liver, and adipose tissue, resulting in amelioration of insulin resistance in HFD-fed mice. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is a systemic microvasculitis predominantly involving the capillaries. We investigated the expression of thrombomodulin (TM) and endothelial cell nitric oxide synthase (eNOS) in microvessels of DM patients. Twelve patients with acute or subacute onset of proximal muscle weakness and erythematous rash over their faces and shoulders were included in this study. Serum creatine phosphokinase was elevated in almost all patients. Electromyograph showed a myopathic pattern in all patients. Muscle biopsies were performed in all patients and 10 non-DM controls and studied with histological, enzyme histochemical and immunohistochemical staining. von Willebrand factor, TM and eNOS antibodies were used as the primary antibodies. Perifascicular degeneration and inflammatory cell infiltration in the perimysium were noted in almost all patients. Non-special esterase staining was markedly positive in capillary and microvascular endothelium. Marked reduction in TM and eNOS staining was noted in DM patients in perimysium microvessels and perifascicular area capillaries. Vascular lesions in DM were not only limited to capillaries. The low expression of TM and eNOS in microvessels suggests the anticoagulation and vasodilation functions of vascular endothelium is reduced. DM is an inflammatory vascular endothelial disease. [ABSTRACT FROM AUTHOR]

The pressure dependence of the yield strength of tantalum was investigated experimentally up to 101 GPa at room temperature using a diamond anvil cell. A yield strength softening is observed between 52 and 84 GPa, whereas a normal trend is observed below 52 GPa and above 84 GPa. The onset pressure of the softening is in agreement with previous results obtained by the pressure gradient method and shock wave experiments. This unusual strength softening in tantalum is not related with structural transformation, preferred orientation, or material damage. Our measurements indicate that microscopic deviatoric strain is the major reason for the observed strength softening in tantalum. [ABSTRACT FROM AUTHOR]

A large amount of waste biomass is produced during agricultural processes, which is a promising renewable energy source, but, to date, there are no effective ways of realizing industrial application of such waste biomass. In the present study, the biomass briquettes produced by waste biomass, which were used as fuel in the curing of flue-cured tobacco, were analyzed. Compared with coal, the average fuel consumption and labor cost of biomass briquettes were down 3.53 and 39.50%, respectively. As for the quality of flue-cured tobacco processed using biomass briquettes, the proportion of superior tobacco leaves increased by 1.23% and the proportion of inferior tobacco leaves decreased by 1.21% compared with those processed using coal. By monitoring the exhaust gases, the emissions of CO2, CO, and SO2 from biomass briquettes were decreased by 57.28, 95.45, and 98.06%, respectively, compared with coal. The results indicated that the biomass briquette is an excellent renewable industrially useful fuel with potential for future application and is an environmentally-friendly fuel, which can be widely used in the drying of agricultural products. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is difficult to manage due to the lack of effective treatments. Increased oxygen consumption caused by ove rnutrition, along with reduced oxygen delivery to liver cells induces hepatic steatosi s. Here, we investigated the efficacy of oxygen therapy (OT) to alleviate hepatic steatosi s. The effect of OT on hepatic steatosis was evaluated in high-fat-diet (HFD)-fed mice and palmitic acid (PA)- treated primary hepatocytes. Liver biopsy tissue samples were u sed to determine the relationship between the expression of hypoxia-inducible fa ctor-2α (HIF-2α) and the progression of NAFLD. The role of HIF-2α in the OT group was determined based on the overexpression of HIF-2α in vitro. OT safely alleviated hepatic hypoxia and improved hepatic steatosis by inhibiting hepatic de novo lipogenesis in HFD-fed mice and PA-treated primary hepatocytes, and this was accompanied by red uced expression of HIF-2α and hepatic de novo lipogenesis. The analysis of liver tissues from individuals wi th or without NAFLD revealed a positive correlation between hepati c HIF-2α expression and NAFLD progression. Overexpression of HIF-2α in vitro inhibited the beneficial effect of OT against hepatic lipogenesis and steatosis. OT might be a via ble treatment option for NAFLD and functions by alleviating hypoxia and inhibiting the l iver HIF-2α signaling pathway. [ABSTRACT FROM AUTHOR]

Brillouin scattering measurements were performed on liquid argon in a diamond anvil cell at various solidification points up to 503 K. With the measured results from the 60° platelet-and 180° back-scattering geometries, the sound velocity, refractive index, experimental equation of state, and adiabatic bulk modulus of liquid argon as a function of pressure were determined. The discrepancy between experimental and previous calculated equation of state indicates that the many-body contribution to the density of liquid argon increases with increasing pressure and decreases with increasing temperature. By analyzing the Brillouin spectra in the coexistence of liquid and solid phase regions, the volume change and latent heat of solid-liquid transformation along the equilibrium curve have been also obtained for the first time. [ABSTRACT FROM AUTHOR]

Objective: Large numbers of people with type 2 diabetes are obese. However, changes in cognition and related brain function in obese people with diabetes have not been characterized. Here, we investigated cognition, olfactory function, and odor-induced brain alterations in these patients and therapeutic effects of glucagon-like peptide 1 receptor agonists (GLP-1Ras) on their psychological behavior and olfactory networks.Research Design and Methods: Cognitive, olfactory, and odor-induced brain activation assessments were administered to 35 obese and 35 nonobese people with type 2 diabetes and 35 control subjects matched for age, sex, and education. Among them, 20 obese individuals with diabetes with inadequate glycemic control and metformin monotherapy received GLP-1Ra treatment for 3 months and were reassessed for metabolic, cognitive, olfactory, and neuroimaging changes.Results: Obese subjects with diabetes demonstrated lower general cognition and olfactory threshold scores, decreased left hippocampal activation, and disrupted seed-based functional connectivity with right insula compared with nonobese subjects with diabetes. Negative associations were found between adiposity and episodic memory and between fasting insulin and processing speed test time in diabetes. Mediation analyses showed that olfactory function and left hippocampus activation mediated these correlations. With 3-month GLP-1Ra treatment, obese subjects with diabetes exhibited improved Montreal Cognitive Assessment (MoCA) score, olfactory test total score, and enhanced odor-induced right parahippocampus activation.Conclusions: Obese subjects with type 2 diabetes showed impaired cognition and dysfunctional olfaction and brain networks, the latter of which mediated adiposity in cognitive impairment of diabetes. GLP-1Ras ameliorated cognitive and olfactory abnormalities in obese subjects with diabetes, providing new perspectives for early diagnosis and therapeutic approaches for cognitive decrements in these patients. [ABSTRACT FROM AUTHOR]

The flutter stability of wind turbine blades is one of the important contents in the research of wind turbines. The bending stiffness of blades has decreased with the development of large-sized wind turbines. To achieve damping flutter-suppressing on the long spanwise blades, perforated damping blade was proposed under the consideration of the structural damping factor and the structural stiffness in this paper. Through the study of the unit cell, the deformation model was established and the structural loss factor of the perforated damping blade was derived. The undamped blade and the perforated damping blade, combined with the relevant parameters of a 1500 kW wind turbine blade, were established to simulate the flutter-suppressing abilities and the structural stability. The dynamic response analysis was accomplished with the large deformation theory, and the MPC algorithm was used to realize grid mobile and data delivery, according to the Newmark time integration method. The comparison results show that the perforated damping blade has both a higher structural damping factor and a better structural stiffness. [ABSTRACT FROM AUTHOR]

Replacement of the exocrine parenchyma by fibrous tissue is a main characteristic of chronic pancreatitis. Understanding the mechanisms of pancreatic fibrogenesis is critical for the development of preventive and therapeutic interventions. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin synthesis, is expressed in patients with chronic pancreatitis. However, it is unknown whether COX-2 can cause chronic pancreatitis. To investigate the roles of pancreatic acinar COX-2 in fibrogenesis and the development of chronic pancreatitis, COX-2 was ectopically expressed specifically in pancreatic acinar cells in transgenic mice. Histopathological changes and expression levels of several profibrogenic factors related to chronic pancreatitis were evaluated. COX-2 was expressed in the pancreas of the transgenic mice, as detected by Western blot analysis. Immunohistochemical staining showed COX-2 was specifically expressed in pancreatic acinar cells. COX-2 expression led to progressive changes in the pancreas, including pancreas megaly, persistent inflammation, collagen deposition, and acinar-to-ductal metaplasia. Quantitative RT-PCR and immunostaining showed that profibrogenic factors were upregulated and pancreatic stellate cells were activated in the COX-2 transgenic mice. Expression of COX-2 in pancreatic acinar cells is sufficient to induce chronic pancreatitis. Targeting this pathway may be valuable in the prevention of chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Purpose Diabetic peripheral neuropathies are the common chronic complications of diabetes, but the diagnosis is insensitive by physical examination in busy outpatients. Here we evaluated the performance of SUDOSCAN in screening diabetic peripheral neuropathies in Chinese type 2 diabetic patients. Methods The study enrolled 180 patients for annually screening. All patients underwent neurological symptoms assessment, clinical examination, nerve conduction studies and cardiovascular autonomic reflex tests. SUDOSCAN was tested and evaluated with electrochemical skin conductance in hands and feet, asymmetry ratio in hands and feet and predicted cardiac neuropathy. Results Patients enrolled had an average age of 56.1 years, 9.8 years of diabetic duration. Patients with diabetic sensorimotor polyneuropathy showed significantly lower electrochemical skin conductance in feet and higher asymmetry ratio in feet compared with those without. Sensitivity and specificity of asymmetry ratio in feet for diagnosing diabetic sensorimotor polyneuropathy were 88.2 % and 46.9 % and area under ROC curve was 0.713. Patients with cardiovascular autonomic neuropathy showed significantly lower electrochemical skin conductance in hands and feet, and higher asymmetry ratio in feet and predicted cardiac neuropathy compared with those without. Sensitivity and specificity of electrochemical skin conductance in feet in diagnosing cardiovascular autonomic neuropathy were 85.6 % and 76.1 % with an area under ROC curve of 0.859. Conclusions SUDOSCAN is a sensitive test to detect diabetic peripheral neuropathy in China and could be an effective screening tool in in busy outpatients and primary health care. [ABSTRACT FROM AUTHOR]

Background Previous national survey suggested that dyslipidemia is an increasing burden in China and more severe in urban population. In this study, we retrospectively analyzed the gender and age differences in lipids and lipoproteins in a large Chinese urban population in Nanjing city. Methods A total of 236, 945 adults (age ≥ 20 years old) who undertook a health check between 2009 and 2015 in our medical examination center were involved in the analysis. Fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride (TG) were measured by standard methods. Results The age-standardized estimates of serum total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride were 4.77 (4.76-4.79), 1.19 (1.18-1.19), 2.53 (2.52-2.54) and 1.74 (1.72-1.76) mmol/L in males (n = 130954), and 4.79 (4.78-4.80), 1.46 (1.45-1.46), 2.44 (2.43-2.45) and 1.21 (1.19-1.22) mmol/L in females (n = 105991), respectively. The prevalence of dyslipidemia was significantly elevated in females above 50 years old, and the peak prevalence of dyslipidemia in males was in the age group of 40-59 years, earlier as compared to females (peaked at 60-69 years old). In addition, an increasing secular trend was observed in LDL cholesterol levels from 2009 to 2015 in both males and females. Conclusions Dyslipidemia is an increasing epidemic in China, characterized by a rising trend of LDL cholesterol. The gender and age differences in serum levels of lipid profile as well as prevalence of dyslipidemia suggested that the middle-age men and postmenopausal women should be the prioritized target for better control of dyslipidemia and early prevention of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. [ABSTRACT FROM AUTHOR]

NTRODUCTION: In Asia, patients with type 2 diabetes mellitus (T2DM) often have suboptimal glycemic control for many years prior to initiating basal insulin. Active titration of basal insulin is also required to improve glycemic outcomes. This pooled analysis was conducted to determine the impact of patient baseline covariates on the required dose of basal insulin and treatment response, for the improved management of Asian patients with T2DM. METHODS: Data on insulin-naïve Asian patients with T2DM who initiated and fully titrated insulin glargine 100 U/mL (Gla-100) for ≥ 20 weeks were pooled from seven randomized, controlled, treat-to-target trials. Covariance and multivariate linear/logistic regression analyses were applied to determine the impact of the baseline covariates on Gla-100 dose (primary outcome) and treatment response (secondary outcomes) at week 24 for patients from Asia (N = 724) and from China alone (n = 249). Based on the multivariate analysis for the primary outcome in the Asian population, a nomogram was developed. RESULTS: The dose of Gla-100 at week 24 was negatively correlated with age and positively correlated with body mass index (BMI) and fasting plasma glucose (FPG) at baseline in both Asian and Chinese populations. In both populations, higher baseline glycated hemoglobin (HbA1c) was associated with a lower reduction in HbA1c from baseline, higher HbA1c at week 24, and a lower chance of achieving HbA1c < 7% at week 24. The constructed nomogram enables calculation of the likely dose of Gla-100 required by Asian patients with T2DM to achieve HbA1c < 7% at week 24. CONCLUSIONS: Higher doses of Gla-100 are likely to be required in younger patients or patients with higher baseline BMI or FPG. The nomogram developed in this study can aid clinicians to titrate the dose of Gla-100 appropriately. Evidence in this pooled analysis also indicates that initiating basal insulin at a lower HbA1c can lead to greater glycemic control. [ABSTRACT FROM AUTHOR]

Derivation of human naïve cells in the ground state of pluripotency provides promising avenues for developmental biology studies and therapeutic manipulations. However, the molecular mechanisms involved in the establishment and maintenance of human naïve pluripotency remain poorly understood. Using the human inducible reprogramming system together with the 5iLAF naïve induction strategy, integrative analysis of transcriptional and epigenetic dynamics across the transition from human fibroblasts to naïve iPSCs revealed ordered waves of gene network activation sharing signatures with those found during embryonic development from late embryogenesis to pre-implantation stages. More importantly, Transcriptional analysis showed a significant transient reactivation of transcripts with 8-cell-stage-like characteristics in the late stage of reprogramming, suggesting transient activation of gene network with human zygotic genome activation (ZGA)-like signatures during the establishment of naïve pluripotency. Together, Dissecting the naïve reprogramming dynamics by integrative analysis improves the understanding of the molecular features involved in the generation of naïve pluripotency directly from somatic cells. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO) contributes to insulin resistance in fat and muscle. In the present study, the role and mechanism of EPO in hepatic insulin resistance were investigated in HepG2 cells. Hepatic insulin resistance was induced by palmitic acid (PA) in the HepG2 cells, which were then treated with EPO (5 or 10 U/ml) or specific phosphoinositide 3-kinase (PI3K) inhibitors, wortmannin or LY294002. EPO treatment significantly increased glycogen levels and reduced the protein expression of phosphoenolpyruvate carboxykinase in the PA-induced HepG2 cells. EPO also inhibited the serine phosphorylation of insulin receptor substrate (IRS)-1 (Ser307) and IRS-2 (Ser473), and increased the protein expression levels of PI3K, phosphorylated (p)-protein kinase B (AKT), p-forkhead box O1 (FOXO1) and p-glycogen synthase kinase 3 (GSK-3) β. In agreement with these result, the expression of p-FOXO1 (Ser256) and p-GSK-3β (Ser9), downstream molecules of AKT, were enhanced by EPO treatment (P<0.05). The specific PI3K inhibitors, LY294002 and wortmannin, markedly inhibited the EPO-mediated increases in p-AKT (Ser473), p-FOXO1 (Ser256) and p-GSK-3β (Ser9) in the PA-induced HepG2 cells (P<0.05). The gene expression levels of tumor necrosis factor-a, interleukin-1β and monocyte chemoattractant protein-1, and the p-c-Jun N-terminal kinase (JNK)/total-JNK ratio were markedly suppressed by EPO treatment. These findings suggested that EPO treatment improved hepatic glucose metabolism, potentially through the IRS/AKT/FOXO1 and GSK-3β signaling pathway, which may be associated with its inhibitory effect on the inflammation-associated response. [ABSTRACT FROM AUTHOR]