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Osteoporosis (OP), a metabolic disorder predominantly impacting postmenopausal women, has seen considerable progress in diagnosis and treatment over the past few decades. However, the intricate interplay between genetic factors and endocrine disruptors (EDCs) in the pathogenesis of OP remains inadequately elucidated. The objective of this research is to examine the environmental pollutants and their regulatory mechanisms that could potentially influence the pathogenesis of OP, in order to establish a theoretical foundation for the targeted prevention and medical management of individuals with OP. Utilizing CTD and GEO datasets, network toxicology and bioinformatics analyses were conducted to identify target genes from a pool of 98 co-associated genes. Subsequently, a novel prediction model was developed employing a multiple machine learning algorithm. The efficacy of the model was validated based on the area under the receiver operating characteristic curve. Finally, real-time quantitative polymerase chain reaction (qRT-PCR) was used to confirm the expression levels of key genes in clinical samples. We have identified significant genes (FOXO3 and LUM) associated with OP and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, immune infiltration analysis, and molecular docking analysis. Through the analysis of these key genes, we have identified 13 EDCs that have the potential to impact OP. Several endocrine disruptors, such as Dexamethasone, Perfluorononanoic acid, genistein, cadmium, and bisphenol A, have been identified as notable environmental pollutants that impact the OP. Molecular docking analysis revealed significant binding affinity of major EDCs to the post-translational protein structures of key genes. This study demonstrates that EDCs, including dexamethasone, perfluorononanoic acid, genistein, cadmium, and bisphenol A, can be identified as important environmental pollutants affecting OP, and that FOXO3 and LUM have the potential to be diagnostic markers for OP. These results elucidate a novel association between EDCs regulated by key genes and the onset of OP., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Many species of Salvia have excellent ornamental, culinary, and medicinal values. Salvia daiguii , is an ornamental and highly medicinal perennial herb endemic to the prefecture-level city of Zhangjiajie in Hunan Province, China, with a narrow geographical distribution. However, currently, it has only been assessed as a Critically Endangered species according to the IUCN classification criteria, but its conservation has not yet been studied. This study investigated the distribution and niche characteristics of S. daiguii , and compared the differences in growth, flowering characteristics, and soil nutrients between the wild and ex situ populations. We also analyzed the effects of soil nutrients on plant growth and flowering characteristics. During the survey, we found 274 individuals on a rock approximately 200 m from ZEFR1. Nevertheless, S. daiguii were still restricted in three populations, TNFP, TGM, and ZEFR in Zhangjiajie City, with a total of about 500 plants and less than 250 mature individuals. Our results show that aspects such as adverse environmental conditions, low seedling renewal rate, a lack of soil nutrients, and competition for the characteristic niche of this and other dominant plants in the natural community are the main ecological factors affecting the growth, flowering, and geographic distribution of S. daiguii . Based on the results of field surveys, we recommend that (1) S. daiguii be classified as Critically Endangered C2b and China's List of Plant Species with Extremely Small Populations. (2) Comprehensive conservation strategies were developed, such as the establishment of nature reserves, reintroduction, public education, and institutional development to provide management recommendations related to the conservation of S. daiguii and other endangered plants., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: Salvia L., representing the largest genus within the mint family, is noted for its global distribution of approximately 1000 species, with East Asia, and particularly China, recognized as a critical center of diversity for the genus., Methods: Our research was conducted through extensive fieldwork in Guidong County, Hunan Province, China, where we identified a previously undescribed species of Salvia . The identification process involved detailed morphological observations, phylogenetic analyses, and plastid genomics., Results: The newly discovered species, Salvia guidongensis , exhibits unique characteristics not commonly observed in the East Asian lineage of Salvia, including dual floral colors within natural populations-either pale purple or pale yellow. Morphologically, while it shares similarities with members of sect. Glutinaria , S. guidongensis is distinct in its floral morphology, stature, and specific foliar traits. Phylogenetic analysis places S. guidongensis in a unique clade within the East Asian lineage of Salvia , suggesting it may serve as an important evolutionary link. Additionally, we explored the plastome features of S. guidongensis , comparing them with those of closely related species., Discussion: The discovery of S. guidongensis not only entriches the taxonomic tapestry of Salvia but also provides critical insights into the biogeography and evolutionary pathways of the genus in East Asia. By integrating morphological and molecular data, we validate the novel status of S. guidongensis and highlight its significance in bridging taxonomic and evolutionary gaps within Sect. Glutinaria of Salvia ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Qi, Feng, Ge, Huang, Feng, Wu, Wei, Ito, Kokubugata, Li and Wei.)

To investigate the possible causal relationship between intestinal microflora and fractures using Mendelian randomization (MR). A 2-sample MR study of gut microbiota and fractures was conducted using a weighted inverse variance analysis with tests for heterogeneity, horizontal pleiotropy, and sensitivity. A causal association between fracture risk and specific bacterial taxa was identified at various taxonomic levels: 2 (Bacteroidia, P = .0304; Deltaproteobacteria P = .0304) at the class level, 3 (Bacteroidales, P = .0428; Desulfovibrionales, P = .0428; Enterobacteriales, P = .0208) at the order level, 2 (FamilyXI, P = .0304; Enterobacteriaceae P = .0332) at the family level, and 1 (Alistipes, P = .0405) at the genus level. This study revealed a causal relationship between gut microflora and fracture risk, demonstrating that the effect of different flora taxa flora abundance on fracture risk differs. It provides a reference for further studies., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To analyze the correlation between microstructure changes in cerebral white matter before and after surgery and early postoperative cognitive function in patients undergoing meningioma resection. Methods: A total of 17 patients who underwent their first meningioma resection at Xuanwu Hospital of Capital Medical University from April 2022 to April 2023 were prospectively included as observation group, with 5 males and 12 females, aged (56.4±7.3) years. Another 15 age- and education-matched patients with cerebral benign tumor were recruited as control group during the same period, with 5 males and 10 females, aged (55.2±8.0) years. Neuropsychological tests (NST), mainly including auditory verbal learning test of Huashan version (AVLT-H), the Montreal cognitive assessment-basic (MoCA-B), clock drawing task-30 (CDT-30), shape trails test-B (STT-B) and animal fluence test (AFT), were conducted at 1 day before surgery, 1 day and within 3-4 days after surgery in the observation group. Simultaneously, magnetic resonance imaging (MRI) scans were performed to collect diffusion tensor imaging (DTI) images at 1 day before surgery and within 3-4 days after surgery. The same NST were conducted at 1 day, 3 days and 6 days after admission in the control group to adjust for learning effects from repeated tests. The microstructure changes of the whole brain white matter were evaluated at the group level by using tract-based spatial statistics (TBSS) technology, including changes of fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD). Then, correlation was performed between DTI indicators with statistically significant and cognitive function. Results: After adjusting for the learning effects, the AVLT-H (R), MoCA-B, and CDT-30 scores decreased, and the evaluation time of STT-B prolonged after surgery in patients with meningioma. And their perioperative decreased values were -0.78 (95% CI :-3.28--0.28) points, -2.22 (95% CI :-4.22--0.72) points, -2.74 (95% CI :-5.29--0.19) points, and 61.49 (95% CI : 5.71-117.27) seconds, respectively, with statistically significant differences (all P <0.05). Group level analysis of TBSS based on DTI images showed decreased FA mainly in the right superior cerebellar peduncle, left posterior limb of internal capsule and genu of corpus callosum, and increased RD mainly in the left anterior corona radiata in patients undergoing meningioma resection, with statistically significant differences (all P FWE <0.05). Linear correlation showed that the perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle were positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects ( r= 0.72, 0.52, all P FWE <0.05). Conclusions: Patients undergoing meningioma resection are at risk of postoperative cognitive decline. Perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle based on DTI images are positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects.

Patients with type 2 diabetes mellitus (T2DM) are at higher risk for urinary tract infections (UTIs), which greatly impacts their quality of life. Developing a risk prediction model to identify high-risk patients for UTIs in those with T2DM and assisting clinical decision-making can help reduce the incidence of UTIs in T2DM patients. To construct the predictive model, potential relevant variables were first selected from the reference literature, and then data was extracted from the Hospital Information System (HIS) of the Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital for analysis. The data set was split into a training set and a test set in an 8:2 ratio. To handle the data and establish risk warning models, four imputation methods, four balancing methods, three feature screening methods, and eighteen machine learning algorithms were employed. A 10-fold cross-validation technique was applied to internally validate the training set, while the bootstrap method was used for external validation in the test set. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the performance of the models. The contributions of features were interpreted using the SHapley Additive ExPlanation (SHAP) approach. And a web-based prediction platform for UTIs in T2DM was constructed by Flask framework. Finally, 106 variables were identified for analysis from a total of 119 literature sources, and 1340 patients were included in the study. After comprehensive data preprocessing, a total of 48 datasets were generated, and 864 risk warning models were constructed based on various balancing methods, feature selection techniques, and a range of machine learning algorithms. The receiver operating characteristic (ROC) curves were used to assess the performances of these models, and the best model achieved an impressive AUC of 0.9789 upon external validation. Notably, the most critical factors contributing to UTIs in T2DM patients were found to be UTIs-related inflammatory markers, medication use, mainly SGLT2 inhibitors, severity of comorbidities, blood routine indicators, as well as other factors such as length of hospital stay and estimated glomerular filtration rate (eGFR). Furthermore, the SHAP method was utilized to interpret the contribution of each feature to the model. And based on the optimal predictive model a user-friendly prediction platform for UTIs in T2DM was built to assist clinicians in making clinical decisions. The machine learning model-based prediction system developed in this study exhibited favorable predictive ability and promising clinical utility. The web-based prediction platform, combined with the professional judgment of clinicians, can assist to make better clinical decisions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiong, Liu, Hu, Zhu, Wei, Yang, Wu and Long.)

To investigate the causal relationship between ever smoked and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with ever smoked and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between ever smoked and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results of ever smoked showed an OR = 2.49, 95% CI = 1.05-5.91, P = .038, indicating that ever smoked is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. This study used two-sample MR analysis to analyze and explore the genetic data, and the results showed a higher prevalence of frozen shoulder in patients with ever smoked, suggesting that active control of ever smoked may reduce the occurrence of frozen shoulder., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between depression and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with depression and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between depression and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an odds ratio (95% confidence interval) of 1.18 (0.91-1.53), P = .204, indicating that depression was not causally related to the development of frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using a two-sample MR analysis, and the results showed no causal relationship between depression and the occurrence of frozen shoulder, requiring the inclusion of a larger sample for the study., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between breast cancer and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with breast cancer and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median (WME) and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between breast cancer and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an OR (95% CI) of 1.02 (1.00-1.04), P = .048, indicating that breast cancer is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using two-sample MR analysis, and the results showed that the incidence of frozen shoulder was higher in breast cancer patients, suggesting that screening for frozen shoulder in breast cancer patients should be increased., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between metformin use and osteoporosis and different subtypes of osteoporosis using a 2-sample Mendelian randomization method. Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variables being osteoporosis and different subtypes. Mendelian randomization was performed using Inverse Variance Weighted (IVW), MR-Egger, and weight median (WM) methods, and heterogeneity tests, horizontal multivariate analyses, and sensitivity analyses were performed. The IVW method analysis with metformin and osteoporosis showed P = 1.53E-04, OR (95%CI) = 1.81E-02 (2.27E-02-1.44E-01); the IVW method analysis with metformin and postmenopausal osteoporosis with pathologic fracture showed P = 2.22E-01, OR (95%CI) = 4.89E-02 (3. 83E-04-6.23E + 00); the IVW method using metformin with osteoporosis with pathological fracture showed that P = 2.14E-01, OR (95%CI) = 1.64E + 00(5.78E-02-6.44E-04); the IVW method using metformin with pharmacological osteoporosis with pathological fracture showed that P = 9. 83E- 01, OR (95%CI) = 1.11E + 00 (3.99E-05-3.11E + 04); IVW method of metformin use and pharmacological osteoporosis showed that P = 5.99E-01, OR (95%CI) = 2.27E + 01 (2.00E-04-2.57E + 06); there is a causal relationship between metformin use and osteoporosis, but there is no causal relationship between metformin use and postmenopausal osteoporosis with pathological fracture, osteoporosis with pathological fracture, pharmacological osteoporosis, and pharmacological osteoporosis with pathological fracture, and metformin use is a protective factor for osteoporosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

From a porous structure perspective, the one-stage de novo synthesis method and impregnation method were applied to synthesize Ag(I) ion-containing ZIF-8 samples. With the de novo synthesis method, Ag(I) ions could be located inside micropores or adsorbed on the external surface of the ZIF-8 by selecting AgNO 3 in water or Ag 2 CO 3 in ammonia solution as precursors, respectively. The ZIF-8 confining Ag(I) ion exhibited a much lower constant releasing rate than the Ag(I) ion adsorbed on the ZIF-8 surface in artificial seawater. As such, strong diffusion resistance in association with the confinement effect is contributed by ZIF-8's micropore. On the other hand, the release of Ag(I) ions adsorbed on the external surface was diffusion limited. Therefore, the releasing rate would reach a maximum not increasing with Ag(I) loading in the ZIF-8 sample.

Objective: To explore the clinical effect of the modified Stoppa combined with Kocher-Langenbeck(K-L) approach and 3D printing technology in the treatment of complex acetabular fractures., Methods: The surgical methods of 70 patients with complex acetabular fractures admitted from April 2013 to July 2019 were retrospectively analyzed. Among them, 25 cases were operated with 3D printing technology(3D printing group) and 45 cases were operated with conventional operation(conventional operation group). The operation time, intraoperative blood loss, intraoperative fluoroscopy times, complications and functional recovery of the hip joint of two groups were recorded., Results: There were statistically significant differences between two groups in terms of operation time, intraoperative bleeding volume and intraoperative fluoroscopy times( P <0.01). All patients were followed up for (15.8±3.5) months, and all patients achieved bony healing. There was no significant difference in the results of Matta reduction between two groups( P >0.05). There was no significant difference in Harris score at 6 months after operation between two groups( P >0.05)., Conclusion: With the aid of 3D printing technology, the improved Stoppa combined with K-L approach is used to treat complex acetabular fractures. It has certain advantages in helping clinicians to formulate a reasonable operation plan before operation, avoid unnecessary operation and trauma during operation, shorten the operation time and reduce the amount of bleeding during operation. It can improve the safety during the perioperative period, facilitate the accurate reduction of fractures during operation and facilitate the recovery of patients.

The unique structure and physical properties of graphene and anatase TiO 2 make them suitable for use as additives for engine lubricants. This study describes the use of dielectric barrier discharge plasma-assisted ball milling to synthesize a multilayer graphene-reinforced TiO 2 composite nanolubricant additive (MGTC). A variety of physical and chemical tests were performed to characterize the resulting experimental materials, including X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Raman, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Four-ball friction and wear testing machines were used to study the tribological properties and extreme pressure anti-wear properties of a base oil containing 0.1, 0.5, 1.0, and 1.5 wt % of the modified TiO 2 . Raman spectroscopy, XPS, SEM, and energy-dispersive spectrometry (EDS) analyses were used to examine and analyze the microstructure of the friction pairs. As a result of the plasma-assisted ball milling process, expanded graphite was successfully separated into multilayer graphene nanosheets, and spherical TiO 2 was successfully bonded to the nanosheets of the multilayer graphene. The 1.0 wt % composite oil was found to provide good friction reduction and wear resistance. It had a film thickness of 27.5 nm, which was 167% thicker than base oil. Due to its excellent dispersion stability, the MGTC nanocomposite exhibited excellent lubrication performance, which was attributed to the formation of carbon protective films, titanium dioxide deposition films, transfer films, and the occurrence of nano ball effects on the surface of friction pairs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The widely cultivated medicinal and ornamental plant sage (Salvia officinalis L.) is an evergreen shrub of the Lamiaceae family, native to the Mediterranean. We assembled a high-quality sage genome of 480 Mb on seven chromosomes, and identified a biosynthetic gene cluster (BGC) encoding two pairs of diterpene synthases (diTPSs) that, together with the cytochromes P450 (CYPs) genes located inside and outside the cluster, form two expression cascades responsible for the shoot and root diterpenoids, respectively, thus extending BGC functionality from co-regulation to orchestrating metabolite production in different organs. Phylogenomic analysis indicates that the Salvia clades diverged in the early Miocene. In East Asia, most Salvia species are herbaceous and accumulate diterpenoids in storage roots. Notably, in Chinese sage S. miltiorrhiza, the diterpene BGC has contracted and the shoot cascade has been lost. Our data provide genomic insights of micro-evolution of growth type-associated patterning of specialized metabolite production in plants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Salvia honania L. H. Bailey is an endemic species, mainly distributed in Henan and Hubei provinces in China. The first complete chloroplast genome of Salvia honania was sequenced and assembled in this study. The genome is 151,559 bp in length and contains 132 encoded genes in total, including 87 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The phylogenomic analysis showed that Salvia honania was closely related to Salvia meiliensis according the current sampling extent., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Vibrational properties associated with the intra- and intermolecular bonding of the crystalline Dibenz[a,h]anthracene at low temperatures are investigated by Raman scattering. A complete characterization of phonon spectra is given for this material. In the 120-150 K temperature region, several lattice modes show abrupt changes of splitting and the discontinuities in the temperature shift, but no emergence of new modes. Moreover, the intensity ratio of I 68 / 38 is greater than 1 below 130 K. Meanwhile, the aromatic C-C stretching modes exhibit anomalous behaviors in frequencies, widths, and intensities at about 130 K. These spectroscopic results demonstrate a disorder-order transition occurred at about 130 K. However, the modes, corresponding to C-H out-of-plane bending, C-H in-plane bending, and/or C-H rocking, have no significant change in the whole temperature range. It indicates that the transition mainly results from the change of the tilt angle between the molecules. Our work is of great significance to understand the internal vibrational properties of Dibenz[a,h]anthracene, and it also provides considerable supports for the further study of this material., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Elsholtziazhongyangii (Lamiaceae), a new species from Sichuan Province, China, is described and illustrated. The new species is morphologically similar to E.feddeif.feddei, but it can be easily distinguished from E.feddeif.feddei by smaller corolla (3.2-3.5 mm vs. 4.5-5.3 mm), bract indumentum (glabrous, except margin ciliate vs. villous, especially on veins abaxially, glabrous adaxially) and bract stalked (ca. 1.2 mm vs. sessile). Phylogenetic analyses, based on two nuclear ribosomal (ETS, ITS) and five plastid ( rbc L, mat K, trn L-F, ycf 1, ycf 1- rps 15) regions, confirmed that the new species formed a monophyletic clade with robust support. The new species is currently known from western Sichuan., (Xin-Jie Jin, Yue Huang, Yu-Kun Wei, Qing Ma, Lu-Xian Liu, Zhi-Xi Fu, Gui-Fang Wu, Yong-Hua Zhang, Pan Li.)

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

The medicinal plant Scutellaria baicalensis Georgi is rich in specialized 4'-deoxyflavones, which are reported to have many health-promoting properties. We assayed Scutellaria flavones with different methoxyl groups on human cancer cell lines and found that polymethoxylated 4'-deoxyflavones, like skullcapflavone I and tenaxin I have stronger ability to induce apoptosis compared to unmethylated baicalein, showing that methoxylation enhances bioactivity as well as the physical properties of specialized flavones, while having no side-effects on healthy cells. We investigated the formation of methoxylated flavones and found that two O-methyltransferase (OMT) families are active in the roots of S. baicalensis. The Type II OMTs, SbPFOMT2 and SbPFOMT5, decorate one of two adjacent hydroxyl groups on flavones and are responsible for methylation on the C6, 8 and 3'-hydroxyl positions, to form oroxylin A, tenaxin II and chrysoeriol respectively. The Type I OMTs, SbFOMT3, SbFOMT5 and SbFOMT6 account mainly for C7-methoxylation of flavones, but SbFOMT5 can also methylate baicalein on its C5 and C6-hydroxyl positions. The dimethoxylated flavone, skullcapflavone I (found naturally in roots of S. baicalensis) can be produced in yeast by co-expressing SbPFOMT5 plus SbFOMT6 when the appropriately hydroxylated 4'-deoxyflavone substrates are supplied in the medium. Co-expression of SbPFOMT5 plus SbFOMT5 in yeast produced tenaxin I, also found in Scutellaria roots. This work showed that both type I and type II OMT enzymes are involved in biosynthesis of methoxylated flavones in S. baicalensis., (© 2021 Shanghai Chenshan Botanical Garden. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Delayed autonomous selfing (DAS) provides reproductive assurance under conditions of pollinator and/or pollen-limitation. Few plant species have been investigated to determine if DAS is terminated when a flower is sufficiently pollinated by a pollen vector, thereby saving plant resources for other purposes. We examined this possibility in bumblebee-pollinated Salvia umbratica . We first showed that DAS resulting in high fruit set (100%) and seed set (>80%) per flower occurred in the absence of insect pollinators by means of style recurvature and was completed in 94% of flowers 72 h after they opened. In contrast, in flowers pollinated immediately after opening, DAS was prevented by corollas dropping away before styles recurve toward the upper thecae. We next showed that hand-pollination of flowers immediately after they opened resulted in high fruit set (100%) and seed set (>80%) when 5-10 pollen grains or more were deposited on their stigmas, whereas fruit set and seed set were reduced to 45.00 and 22.50%, respectively, when pollen loads were reduced to 1-3 pollen grains. Finally, we showed that on average single pollinator visits deposited 26 pollen grains on stigmas of flowers that had just opened, which is more than enough to ensure high fruit and seed set. Our results indicate that flower longevity is highly correlated with the pollinator environment and female fitness of S . umbratica , with extended flower longevity allowing DAS to occur being advantageous when pollinators are absent, while reduced floral longevity and prevention of DAS being favored when flowers are pollinated by pollinators. Thus, flower longevity in S. umbratica varies so as to optimize reproductive output and resource efforts, and is dependent on the availability and effectiveness of pollinators to pollinate flowers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiao, Huang, Chang, Chen, Abbott, Wei and Ma.)

Red sage ( Salvia miltiorrhiza ) is a widely used medicinal plant for treatment of cardiovascular and cerebrovascular diseases. Because of excessive excavation by huge market demand and habitat loss by human activities, the wild population resources of S. miltiorrhiza have reduced drastically in recent years. Meanwhile, population status of two closely related species S. bowleyana and S. paramiltiorrhiza were in a trend of decreasing due to their potential replacement of S. miltiorrhiza . Particularly, S. paramiltiorrhiza was threatened and endemic to a small region in eastern China. However, to date there has been no conservation genetic research reported for wild S. miltiorrhiza population and its endangered relatives. Assess the wild germplasm diversity for S. miltiorrhiza and its related species would provide fundamental genetic background for cultivation and molecular breeding of this medicinally important species. In the present study, we investigated the genetic diversity, population structure, and intra/inter-specific differentiation of S. miltiorrhiza and above two relatives using 2b-RAD genome-wide genotyping method. By investigating 81 individuals of S. miltiorrhiza , 55 individuals of S. bowleyana and 15 individuals of S. paramiltiorrhiza from 23 locations in China, we obtained 23,928 SNPs in total. A comparatively high genetic diversity was observed in S. miltiorrhiza (π = 0.0788, H e = 0.0783 ± 0.0007). The observed and expected heterozygosity in populations of these three species ranged from 0.0297 to 0.1481 and 0.0251 to 0.831, respectively. Two major lineage groups were detected in the examined S. miltiorrhiza populations. The results indicated that Dabie Mountain as a genetic diversity center of S. miltiorrhiza and possible complex inter-specific genetic exchange/hybridization occurred between S. miltiorrhiza and the two relatives. We suggest that strategic conservation and germplasm preservation should be considered not only for wild populations of S. miltiorrhiza , but also for its related S. bowleyana and S. paramiltiorrhiza., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Zhang, Huang, Xiao, Wu, Qi and Wei.)

The complete chloroplast genome of Zhangjiajie sage, Salvia daiguii , was assembled in this study. The genome is 151,434 bp in length and contained 134 encoded genes in total, including 88 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The result of phylogenetic analysis based on 17 chloroplast genomes revealed that S. daiguii is clustered with Salvia miltiorrhiza in Lamiaceae., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To analyze the incidence and characteristics of fabella in the Chinese population and its correlation with pain in the posterolateral region of the knee joint and common peroneal nerve palsy., Methods: Total 732 patients including 405 males(450 knees) and 327 females(383 knees) who underwent unilateral or bilateral knee MR imaging from September 2015 to July 2019 were retrospectively evaluated. The basic information of all patients was extracted from the hospital's his system. The patient's medical records were checked by telephone follow-up or his system, and the number of patients with posterolateral knee pain and common peroneal nerve paralysis were recorded., Results: The overall prevalence of fabella was 48.38%, 23.53% in men and 24.85% in women, there was no significant difference between them ( P >0.05). All the subjects were divided into five age groups. The prevalence of fabella was significantly different among different age groups:6.6% in 20 year-old group, 33.8% in 21 to 34-year-old group, 53.5% in 35 to 44-year-old group, 57.5% in 45 to 59-year-old group and 73.9% in ≥ 60-year-old group, the difference was statistically significant ( P <0.001). There was a significant correlation between the prevalence of fabella and the age of patients. With the increase of patients' age, the prevalence of fabella in knee joint also showed an obvious upward trend ( P <0.001). According to the presence of fabella in the knee joint, 232 cases of knee joint pain were found, accounting for 57.57% of the patients with fabella, accounting for 27.85% of the total data( P <0.01). The correlation score analysis was R =1.546, P <0.01;when the presence of fabella in the knee joint, a total of 44 cases of common peroneal nerve paralysis occurred in the knee joint, accounting for all knees 28% of the total knee joint, and 29 cases of common peroneal nerve palsy (3.48% of the total knee joint) were found when there was no fabella in the knee joint( P <0.05). The correlation score analysis was performed with R =1.695, P <0.05., Conclusion: The prevalence of fabella us in Chinese population is 48.38%. There is no relationship between the incidence of gastrocnemius and gender, but the incidence of fabella is positively correlated with age, pain in the posterolateral region of the knee joint and the occurrence of common peroneal nerve symptoms.

Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K-Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein-protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K-Akt-mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

The complete chloroplast genome of Russian sage Salvia yangii B. T. Drew was assembled in this study. The genome is 151,473 bp in length and contained 129 encoded genes in total, including 84 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The result of phylogenetic analysis based on 15 chloroplast genomes revealed that S. yangii is closely related to common sage ( Salvia officinalis ) in Lamiaceae., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Salvia miltiorrhiza(Sm) and Salvia castanea f. tomentosa(Sc) hairy roots were used as experimental materials to study the effects of six different carbon sources, galactose, fructose, lactose, glucose, arabinose and sucrose(control), on fresh weight, dry weight, contents and yields of salvianolic acids and tanshinones. The results showed that galactose was most beneficial to the growth of two kinds of hairy roots, while lactose and arabinose were not conducive to their growth. As for Sm hairy roots, fructose significantly promoted the accumulation of salvianolic acid B, and the content increased by 5.801 times and 10.151 times compared with the control group, respectively. Glucose significantly promoted the accumulation of salvianolic acids. The content and yield of rosmarinic acid were 7.674 times and 9.260 times of that of the control group, and the content and yield of salvianolic acid B were 5.532 times and 6.675 times of the control group. For the hairy roots of Sc, galactose significantly increased the content and yield of rosmarinic acid, reaching 7.820 times and 9.944 times of the control group, respectively. Fructose promoted the increase of the content and yield of cryptotanshinone, reaching 9.242 times and 6.609 times of the control group, respectively. The study confirmed the optimal carbon source for the hairy root culture of Sm and Sc, and provided theoretical guidance for large-scale production of Sm drug-derived components and the utilization of Sc.

The lily-of-the-valley Convallaria (Asparagaceae) consists of three herbaceous perennial species. The plants are commonly found in northern hemisphere, and are best-known for their ornamental and pharmaceutical value. In order to assess the genetic structure, diversity and demographic history of Convallaria species, 19 novel microsatellite markers were developed based on transcriptome data of C. keiskei. Polymorphism and cross-amplification of the markers were tested in three populations of C. keiskei and one population each of C. majalis and C. montana. The transferability rate in two species was both 89.5%. The average number of alleles detected per locus was 7.7, 3.3 and 2.7 in C. keiskei, C. majalis and C. montana, respectively, and the polymorphism information content correspondingly varied from 0.067 to 0.730, from 0.071 to 0.637 and from 0.195 to 0.680 at the population level. The observed and expected heterozygosity ranged from 0.000 to 1.000 and from 0.000 to 0.833, respectively. Seven of the 19 loci showed significant deviation from Hardy-Weinberg equilibrium. The availability of these markers will provide a useful molecular tool for further population genetics, phylogeographic and breeding studies of Convallaria species.

The limited treatment options and therapeutic failure due to acquired resistance for patients with triple-negative breast cancer (TNBC) represent a significant challenge. Inhibitors against poly (ADP-ribose) polymerase (PARP), olaparib and talazoparib, were recently approved for the treatment of metastatic breast cancer (including TNBC) in patients with germline BRCA1/2 mutations. Despite impressive response rates of ~60%, the prolongation in median progression-free survival with a PARPi is modest, suggesting the emergence of resistance. Several studies have reported that receptor tyrosine kinases (RTKs), such as c-MET (also known as hepatocyte growth factor receptor), are involved in resistance to various anti-neoplastic agents, including PARPi. However, the mechanism by which c-MET contributes to acquired resistance to PARPi in TNBC is not fully understood. In this study, we show that hyperactivated c-Met is detected in TNBC cells with acquired resistance to PARPi, and the combination of talazoparib and crizotinib (a multi-kinase inhibitor that inhibits c-MET) synergistically inhibits proliferation in these cells. Unexpectedly, depleting c-MET had limited effect on talazoparib sensitivity in PARPi-resistant cells. Interestingly, we found evidence of epidermal growth factor receptor (EGFR) hyperactivation and interaction of EGFR/c-Met in these cells. Notably, combining EGFR and PARP inhibitors resulted in greater inhibition of proliferation in c-MET-depleted TNBC cells, and combined c-MET and EGFR inhibition increased sensitivity to talazoparib in TNBC cells with acquired resistance to PARPi. Our findings suggest that combined inhibition of c-MET and EGFR could potentially re-sensitize TNBC to the cytotoxic effects of PARPi., Competing Interests: Dr. Litton has received grant and/or research support from Novartis, Medivation/Pfizer, Genentech, GSK, EMD-Serono, Astra-Zeneca, Medimmune, Zenith and Jounce; served in Speaker’s Bureau for MedLearning, Physician’s Education Resource, Prime Oncology, Medscape, and Clinical Care Options; is an advisory committee, review panel, and/or board member of Astra-Zeneca, Pfizer (all uncompensated), NCCN, ASCO, NIH PDQ., (AJCR Copyright © 2020.)

Cancer-related mortality is a leading cause of death among both men and women around the world. Target-specific therapeutic drugs, early diagnosis, and treatment are crucial to reducing the mortality rate. One of the recent trends in modern medicine is "Theranostics," a combination of therapeutics and diagnosis. Extensive interest in magnetic nanoparticles (MNPs) and ultrasmall superparamagnetic iron oxide nanoparticles (NPs) has been increasing due to their biocompatibility, superparamagnetism, less-toxicity, enhanced programmed cell death, and auto-phagocytosis on cancer cells. MNPs act as a multifunctional, noninvasive, ligand conjugated nano-imaging vehicle in targeted drug delivery and diagnosis. In this review, we primarily discuss the significance of the crystal structure, magnetic properties, and the most common method for synthesis of the smaller sized MNPs and their limitations. Next, the recent applications of MNPs in cancer therapy and theranostics are discussed, with certain preclinical and clinical experiments. The focus is on implementation and understanding of the mechanism of action of MNPs in cancer therapy through passive and active targeting drug delivery (magnetic drug targeting and targeting ligand conjugated MNPs). In addition, the theranostic application of MNPs with a dual and multimodal imaging system for early diagnosis and treatment of various cancer types including breast, cervical, glioblastoma, and lung cancer is reviewed. In the near future, the theranostic potential of MNPs with multimodality imaging techniques may enhance the acuity of personalized medicine in the diagnosis and treatment of individual patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Lung adenocarcinoma (LUAD) is a heterogeneous disease with poor survival in the advanced stage and a high incidence rate in the world. Novel drug targets are urgently required to improve patient treatment. Therefore, we aimed to identify therapeutic targets for LUAD based on protein-protein and protein-drug interaction network analysis with neural network algorithms using mRNA expression profiles., Results: A comprehensive meta-analysis of selective non-small cell lung cancer (NSCLC) mRNA expression profile datasets from Gene Expression Omnibus were used to identify potential biomarkers and the molecular mechanisms related to the prognosis of NSCLC patients. Using the Network Analyst tool, based on combined effect size (ES) methods, we recognized 6566 differentially expressed genes (DEGs), which included 3036 downregulated and 3530 upregulated genes linked to NSCLC patient survival. ClueGO, a Cytoscape plugin, was exploited to complete the function and pathway enrichment analysis, which disclosed "regulated exocytosis", "purine nucleotide binding", "pathways in cancer", and "cell cycle" between exceptionally supplemented terms. Enrichr, a web tool examination, demonstrated "early growth response protein 1 (EGR-1)", "hepatocyte nuclear factor 4α (HNF4A)", "mitogen-activated protein kinase 14 (MAP3K14)", and "cyclin-dependent kinase 1 (CDK1)" to be among the most prevalent TFs and kinases associated with NSCLC. Our meta-analysis identified that MAPK1 and aurora kinase (AURKA) are the most obvious class of hub nodes. Furthermore, protein-drug interaction network and neural network algorithms identified candidate drugs such as phosphothreonine and 4-(4-methylpiperazin-1-yl)-n-[5-(2-thienylacetyl)-1,5-dihydropyrrolo[3,4-c]pyrazol-3-yl] benzamide and for the targets MAPK1 and AURKA, respectively., Conclusion: Our study has identified novel candidate biomarkers, pathways, transcription factors (TFs), and kinases associated with NSCLC prognosis, as well as drug candidates, which may assist treatment strategy for NSCLC patients., (Copyright © 2018. Published by Elsevier Inc.)

Objective: Acute kidney injury (AKI) is common in critically ill patients, and sepsis patients with AKI had a higher mortality rate. The aim of the present study was to determine the potential value of urinary miR-26b in the diagnosis of sepsis-associated AKI., Patients and Methods: Urinary samples were collected from a cohort of 155 sepsis patients (68 AKI patients and 87 non-AKI patients) and 57 patients with non-infectious systemic inflammatory response syndrome (SIRS). The expression levels of urinary miR-26b were measured by RT-qPCR analysis. ROC curve analysis was performed to determine the diagnostic value. Pearson correlation analysis was performed to assess the levels of urinary miR-26b and several clinical parameters. Kaplan-Meier curves were plotted to show the impact of urinary miR-26b on the 28-day survival., Results: Significantly increased urinary miR-26b levels were found in patients with sepsis-associated AKI. Urinary miR-26b had a sensitivity of 90.8% and specificity of 75.0% for distinguishing between AKI sepsis and non-AKI sepsis. Urinary miR-26b levels were closely correlated with clinical parameters reflecting the severity of the disease. Kaplan-Meier analysis revealed that sepsis patients with high urinary miR-26b levels had an elevated mortality rate., Conclusions: Taken together, these findings suggested that urinary miR-26b might be utilized as a potential biomarker for sepsis-associated AKI.

Aflatoxins are sequential of derivatives of coumarin and dihydrofuran with similar chemical structures and well-known carcinogenic agent. Many studies performed to detoxify aflatoxins, but the result is not ideal. Therefore, we studied structural, infrared spectrum, mechanical, and optical properties of these compounds in the aim of perspective physics. Mulliken charge distributions and infrared spectral analysis performed to understand the structural difference between the basic types of aflatoxins. In addition, the effect of pressure, different polarized, and incident directions on their structural changes was determined. It is found that AFB 1 is most stable structure among four basic types aflatoxins (AFB 1 , AFB 2 , AFG 1 , and AFG 2 ), and IR spectra are analyzed to exhibit the difference on structures of them. The mechanical properties of AFB 1 indicate that the structure of this toxin can be easily changed by pressure. The real [Formula: see text] and imaginary [Formula: see text] parts of the dielectric function, and the absorption coefficient [Formula: see text] and energy loss spectrum [Formula: see text] were also obtained under different polarized and incident directions. Furthermore, biological experiments needed to support the toxic level of AFB 1 using optical technologies.

Aim: The new radioimmunotherapeutic regime GAP15R aims to stimulate glucocorticoid-induced TNF-related protein (G) to overcome Treg suppression; add IFN-α (A) to promote inflammatory milieu; block PD1 (P) to disinhibit T effector cytotoxicity; add IL-15 (15) to enhance danger signals & T-cell expansion; and apply radiation (R) at critical time point to sustain localized inflammation. Patients & methods/materials & methods: This was tested in a murine 4T1 metastatic breast carcinoma model given GAP15R with regular monitoring of tumor volume and complications., Results: We had demonstrated long-term complete remission up to 50% of treated mice, which is not associated with major treatment-related complication, in cases with specific tumor burden., Conclusion: GAP15R is efficacious with potential to be applicable to other tumors.

Objective: To investigate the clinical efficacy of enhanced recovery after surgery(ERAS) in atrial caval shunting (ACS) for type Ⅱ Budd-Chiari syndrome(BCS). Methods: The clinical data of patients underwent ACS for type Ⅱ BCS in the Henan Province People's Hospital from January 2014 to June 2016 were prospectively analyzed.Randomized and single-blind, controlled study was performed among the patients, and all of them underwent ACS and were divided into control group (patients underwent traditional perioperative management) and ERAS group (patients underwent ERAS perioperative management) based on a random number table.Operational and postoperative data, levels of inflammatory cytokines, stress state evaluation and postoperative complications were observed.The comparison between the two groups was evaluated with an independent sample t test.The trend analyses for variables were done using repeated measures ANOVA.The count data were analyzed using the chi-square test or Fisher exact. Results: Eighty-two patients were screened for eligibility, and allocated into the control group (40 patients) and the ERAS group (42 patients). All patients underwent ACS successfully with no death.Comparison of intraoperative status: operation time, volume of intraoperative blood and number of patients receiving blood transfusion were (211.0±12.9) minutes vs . (207.7±10.7) minutes, (167.5±28.3) ml vs . (165.0±28.4) ml and 3 cases vs . 1 case between the control group and the ERAS group, respectively, showing no difference between the two groups ( t =0.90, 0.29, χ 2 =0.32, all P >0.05). Comparison of postoperative status: time of gastric tube removal, time of catheter removal, time of chest tube, time to flatus, time of food intake, duration of postoperative infusion, duration of postoperative hospital stay and numeric rating scale were (3.7±0.5)days vs . (0.0±0.0)days, (2.3±0.7)days vs . (1.4±0.5)days, (3.7±0.7)days vs . (2.3±0.5)days, (75.2±3.8)hours vs . (46.6±4.2)hours, (75.7±4.7)hours vs . (21.4±2.1)hours, (10.0±1.0)days vs . (5.8±0.9)days, (11.4±1.0)days vs . (7.8±0.6)days, 2.9±0.4 vs . 1.9±0.6 between the control group and the ERAS group, respectively, with statistically differences ( t =35.03, 4.36, 8.10, 22.89, 47.78, 14.75, 14.22, 6.13, all P <0.05). Stress state evaluation: the levels of IR were (2.7±0.1) vs .(2.7±0.1), (8.8±0.7) vs . (5.2±0.3), (11.0±0.5) vs . (7.3±0.5), (4.9±0.2) vs . (3.9±0.1), and the levels of C-reaction protein were (14.6±1.3)mg/L vs .(14.6±1.1) mg/L, (101.2±13.6) mg/L vs . (89.5±6.9) mg/L, (62.7±8.6) mg/L vs . (56.4±8.4) mg/L, (46.4±6.7) mg/L vs . (40.0±5.6) mg/L from pre-operation to postoperative day 1, 3 and 5 between the control group and the ERAS group, respectively, with statistically significant differences in changing trends( F =136.61, 4.97, both P <0.05). Comparisons of levels of inflammatory cytokines: the levels of IL-6 were (43.1±2.7) ng/L vs . (43.6±3.6) ng/L, (135.1±6.4) ng/L vs . (117.4±5.7) ng/L, (145.4±6.7) ng/L vs . (128.5±5.5) ng/L, (93.3±3.7) ng/L vs . (88.0±3.9) ng/L, and the levels of TNF-α were (10.4±0.3)mmol/L vs . (10.4±0.3) mmol/L, (14.4±0.4) mmol/L vs . (12.6±0.4) mmol/L, (15.6±0.4) mmol/L vs . (13.8±0.4) mmol/L, (12.3±0.7) mmol/L vs . (11.4±0.6) mmol/L from pre-operation to postoperative day 1, 3 and 5 between the control group and the ERAS group, respectively, with statistically significant differences in changing trends ( F =15.15, 21.45, both P <0.05). Comparison of postoperative complications: incidence of complications was 30.0%(12/40) in the control group and 11.9%(5/42) in the ERAS group, and the numbers of patients with nausea and vomiting, respiratory complications and cardiovascular complications were 4, 3, 5 cases in the control group and 3, 1, 1 case in the ERAS group, respectively, showing statistically differences in the incidence of complications(χ 2 =4.08, P <0.05). All the 82 patients were followed up for 2 to 22 months (median time, 12 months), no patients received reoperation or re-admitted to the hospital duo to complications. Conclusion: ERAS management in the perioperative period of ACS for BCS is beneficial to postoperative recovery of patients, and can relieve postoperative stress state and inflammatory response, reduce the duration of hospital stay, and incidence of postoperative complications.

Background: Age-related decline in kidney function can be an important risk factor for cognitive impairment in older adults. In this study, we examined several kidney function measures for the association with cognitive function in older adults in hope to identify early and sensitive markers that can be used for the detection or screening for cognitive impairment., Methods: A total of 1982 older participants (aged ≥60years) in the 1999-2002 National Health and Nutrition Examination Survey was analyzed for the association between kidney function and cognitive impairment using multivariate logistic regression and general linear models. Cognitive functioning was assessed during the household interview using a version of the Digit Symbol Substitution Test of the Wechsler Adult Intelligence Scale III. In our study, participants with a score of <31, the 25th percentiles of the distribution, or who were unable to complete the sample exercise due to cognitive limitations were classified as having cognitive impairment., Results: Of 1982 older adults, 503 were having cognitive impairment (weighted prevalence, 15.38%). Among the kidney function measures that we examined, the levels of serum cystatin C and urinary albumin were found being significantly associated with cognitive impairment after adjusting for age, sex, race/ethnicity, poverty status, education, physical activity, BMI, cigarette smoking, and alcohol consumption. Cognitive functioning scores were significantly decreasing with increasing levels of kidney dysfunction markers., Conclusion: Serum cystatin C and urinary albumin that are early markers of chronic kidney disease might serve as early and effective markers for cognitive decline in older adults. Mechanisms underlying the observed association need to be further characterized., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Within the airway management field, simulation has been used as a tool of training for over 40 years. Simulation training offers a chance of active involvement for the trainees. It can effectively enhance and upgrade the knowledge and skills of the trainees in airway management, and subsequently decrease medical errors and improve patients' outcomes and safety through a variety of airway management training modalities, such as common airway skills, difficult airway management strategies, and crisis management skills. To perform simulation-based airway management training effectively, not only are task trainers and high-fidelity simulators required but also instructors with rich experience in airway management simulation training and optimal curriculum design are essential.

The aim of our study was to conduct a case-control study in a Chinese postmenopausal population to evaluate the roles of the IGF-1 rs35767 and rs972936 polymorphisms on bone mineral density (BMD) levels and osteoporosis risk. A total of 272 consecutive postmenopausal women with a primary diagnosis of osteoporosis and 272 controls were enrolled in the study between 2012 and 2014. The polymerase chain reaction-restriction fragment length polymorphism method was used to genotype the rs35767 and rs972936 IGF-1 polymorphisms. By comparing the demographic characteristics between patients and controls, patients with osteoporosis were found to be more likely to have a habit of alcohol drinking (P = 0.023). Furthermore, the BMD levels of the L1-L4 vertebrae, femoral necks, total hips, and trochanters in patients with osteoporosis were significantly lower than those in controls. By conditional regression analysis, we found that the IGF-1 rs2288377 and rs972936 gene polymorphisms were not associated with the risk of osteoporosis (P < 0.05). However, the CT+TT genotype of rs35767 and the AG+GG genotype of rs972936 were significantly associated with lower BMD levels in the femoral neck. Overall, our study suggests that IGF-1 rs2288377 and rs972936 gene polymorphisms do not influence the risk osteoporosis.

Two dimeric abietane diterpenoids, salviwardins A and B (1 and 2), and a seco-abietane diterpenoid salviwardin C (3), along with five known analogues (4-8), were isolated from the roots of Salvia wardii. The structures of these isolates were elucidated by extensive spectroscopic methods. The inhibitory activities of these isolates against five human cancer cell lines in vitro were also tested.

Cytochrome P450 1B1 (CYP1B1) plays an important role in breast cancer development and progression by bioactivating endogenous estrogens and environmental carcinogens. In this study, we examined the effect of the soy isoflavone genistein on CYP1B1 gene expression, reactive oxygen species (ROS) production, and cell proliferation in human breast cancer MCF-7 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed a dose-dependent induction of CYP1B1 gene expression in the cells treated with 5 and 25 μM of genistein. Genistein at 5 μM exhibited a synergistic effect on the CYP1B1 mRNA level induced by the environmental carcinogen 7,12-dimethylbenz[a]anthracene. We also found that genistein at 5 μM increased cellular levels of ROS and stimulated cell proliferation starting from the second day of culture. This study suggests that physiological concentrations of genistein stimulate ROS production and breast cancer cell proliferation through the induction of CYP1B1 gene expression. More extensive studies are warranted to further characterize the role of genistein and the CYP1B1 enzyme in human breast carcinogenesis.

Molecular dynamics simulations in conjunction with multiscale shock technique (MSST) are performed to study the initial chemical processes and the anisotropy of shock sensitivity of the condensed-phase HMX under shock loadings applied along the a, b, and c lattice vectors. A self-consistent charge density-functional tight-binding (SCC-DFTB) method was employed. Our results show that there is a difference between lattice vector a (or c) and lattice vector b in the response to a shock wave velocity of 11 km/s, which is investigated through reaction temperature and relative sliding rate between adjacent slipping planes. The response along lattice vectors a and c are similar to each other, whose reaction temperature is up to 7000 K, but quite different along lattice vector b, whose reaction temperature is only up to 4000 K. When compared with shock wave propagation along the lattice vectors a (18 Å/ps) and c (21 Å/ps), the relative sliding rate between adjacent slipping planes along lattice vector b is only 0.2 Å/ps. Thus, the small relative sliding rate between adjacent slipping planes results in the temperature and energy under shock loading increasing at a slower rate, which is the main reason leading to less sensitivity under shock wave compression along lattice vector b. In addition, the C-H bond dissociation is the primary pathway for HMX decomposition in early stages under high shock loading from various directions. Compared with the observation for shock velocities V(imp) = 10 and 11 km/s, the homolytic cleavage of N-NO2 bond was obviously suppressed with increasing pressure.

The electronic structure and initial decomposition in high explosive HMX under conditions of shock loading are examined. The simulation is performed using quantum molecular dynamics in conjunction with multi-scale shock technique (MSST). A self-consistent charge density-functional tight-binding (SCC-DFTB) method is adapted. The results show that the N-N-C angle has a drastic change under shock wave compression along lattice vector b at shock velocity 11 km/s, which is the main reason that leads to an insulator-to-metal transition for the HMX system. The metallization pressure (about 130 GPa) of condensed-phase HMX is predicted firstly. We also detect the formation of several key products of condensed-phase HMX decomposition, such as NO2, NO, N2, N2O, H2O, CO, and CO2, and all of them have been observed in previous experimental studies. Moreover, the initial decomposition products include H2 due to the C-H bond breaking as a primary reaction pathway at extreme condition, which presents a new insight into the initial decomposition mechanism of HMX under shock loading at the atomistic level.

We have performed quantum-based multiscale simulations to study the initial chemical processes of condensed-phase octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) under shock wave loading. A self-consistent charge density-functional tight-binding (SCC-DFTB) method was employed. The results show that the initial decomposition of shocked HMX is triggered by the N-NO(2) bond breaking under the low velocity impact (8 km/s). As the shock velocity increases (11 km/s), the homolytic cleavage of the N-NO(2) bond is suppressed under high pressure, the C-H bond dissociation becomes the primary pathway for HMX decomposition in its early stages. It is accompanied by a five-membered ring formation and hydrogen transfer from the CH(2) group to the -NO(2) group. Our simulations suggest that the initial chemical processes of shocked HMX are dependent on the impact velocity, which gain new insights into the initial decomposition mechanism of HMX upon shock loading at the atomistic level, and have important implications for understanding and development of energetic materials.

A pot experiment was conducted to study the effects of inoculation with root-knot nematodes on the cucumber leaf N and P contents, and the rhizospheric and non-rhizospheric soil pH and enzyme activities. The rhizospheric soil pH didn't have a significant decrease until the inoculation rate reached 6000 eggs per plant. With the increase of inoculation rate, the leaf N and P contents, rhizospheric soil peroxidase activity, and rhizospheric and non-rhizospheric soil polyphenol oxidase activity all decreased gradually, rhizospheric soil catalase activity was in adverse, non-rhizospheric soil pH decreased after an initial increase, and non-rhizospheric soil catalase activity had no regular change. After inoculation, rhizospheric soil urease activity decreased significantly, but rhizospheric and non-rhizospheric soil phosphatase activity and non-rhizospheric soil peroxidase activity only had a significant decrease under high inoculation rate. In most cases, there existed significant correlations between rhizospheric soil pH, enzyme activities, and leaf N and P contents; and in some cases, there existed significant correlations between non-rhizospheric soil pH, enzyme activities, and leaf N and P contents.

Object: The standard transsphenoidal approach has been successfully used to resect most pituitary adenomas. However, as a result of the limited exposure provided by this procedure, complete surgical removal of pituitary adenomas with parasellar or retrosellar extension remains problematic. By additional bone removal of the cranial base, the extended transsphenoidal approach provides better exposure to the parasellar and clival region compared with the standard approach. The authors describe their surgical experience with the extended transsphenoidal approach to remove pituitary adenomas invading the anterior cranial base, cavernous sinus (CS), and clivus., Methods: Retrospective analysis was performed in 126 patients with pituitary adenomas that were surgically treated via the extended transsphenoidal approach between September 1999 and March 2008. There were 55 male and 71 female patients with a mean age of 43.4 years (range 12-75 years). There were 82 cases of macroadenoma and 44 cases of giant adenoma., Results: Gross-total resection was achieved in 78 patients (61.9%), subtotal resection in 43 (34.1%), and partial resection in 5 (4%). Postoperative complications included transient cerebrospinal rhinorrhea (7 cases), incomplete cranial nerve palsy (5), panhypopituitarism (5), internal carotid artery injury (2), monocular blindness (2), permanent diabetes insipidus (1), and perforation of the nasal septum (2). No intraoperative or postoperative death was observed., Conclusions: The extended transsphenoidal approach provides excellent exposure to pituitary adenomas invading the anterior cranial base, CS, and clivus. This approach enhances the degree of tumor resection and keeps postoperative complications relatively low. However, radical resection of tumors that are firm, highly invasive to the CS, or invading multidirectionally remains a big challenge. This procedure not only allows better visualization of the tumor and the neurovascular structures but also provides significant working space under the microscope, which facilitates intraoperative manipulation. Preoperative imaging studies and new techniques such as the neuronavigation system and the endoscope improve the efficacy and safety of tumor resection.

We sampled five Achnatherum sibiricum populations and documented the distribution and abundance of endophytes. In total, 438 fungal isolates were obtained. They were classified into 11 morphotypes based on growth rate and morphological characters including colonial morphology, the production of conidiogenous cells, conidial size and dimension on potato dextrose agar medium. Both tub2 and actG sequences identified only a single product in all representative isolates from three dominant morphotypes. All sequences fell in the same main clade, including Neotyphodium gansuense and Neotyphodium gansuense var. inebrians from another Achnatherum species in North China, Achnatherum inebrians, and Neotyphodium guerinii from European grasses Melica ciliate and Melica transsilvanica. Based on both morphological and phylogenetic analyses, isolates in morphotype I were described as representing a novel Neotyphodium species, Neotyphodium sibiricum sp. nov. Isolates in both morphotype II and III were identified as representing N. gansuense. Both tub2 and actG sequences suggested that N. sibiricum and N. guerinii were probably derived from a common Epichloë ancestor.

This paper describes a new infrared (IR) sensing scheme for the determination of arginine (Arg). In this method, the surface of an IR evanescent wave sensing element was modified with sulfonic acid groups to selectively interact with Arg through specific interactions with its guanidine moiety. The sulfonated sensing phase was prepared using a two-layer modification approach. To demonstrate that this assembly could be used for selective infrared sensing, a large number of amino acids were subjected to analysis. Although the sulfonate groups on the surface of the sensing element did interact selectively with the guanidine groups of Arg species, lysine and histidine units caused some interference; this problem could be minimized because of the unique IR absorption bands of the guanidine moiety of Arg. To optimize the detection conditions, we studied the effects of both the pH and the composition of the polymer. The most intense signal was obtained at pH 9. We observed different adsorption rates for the detection of Arg at different values of pH, which we attribute to changes in the accessibility of the analytes to the pore structures of the sensing phase. The composition of the base polymer was also optimized; 60% PVBC (w/w) provided a water-stable, sensitive phase for the detection of Arg in aqueous solution. Under the optimized conditions, we obtained a linear range of detection up to 0.1mM with a detection limit of ca. 5microM.

Objective: To investigate the feasibility of inducing adult human myoblasts into neural precursor cells., Methods: The myoblasts were isolated with mixed digestive enzyme from minced human temporal muscle samples, cultured and purified clonally. The 3rd passage cells were incubated with serum free medium including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and leukemia inhibitory factor (LIF). Morphological change was investigated during incubation period. Immunofluorescence cytochemistry and RT-PCR analysis were used to assess cell differentiation and trans differentiation., Results: After the induction, cells became non-adherent aggregates as neurospheres. The myoblast-derived neurospheres was immuno-positive for nestin. In differentiation condition, they looked like neurons and glial cells and expressed neuronal (microtubule associated protein 2, MAP-2), astrocytic (Glial fibrillary acidic protein, GFAP) and oligodendrocytic (Galactocerebroside, Galc) markers by immunocytochemistry. The result by RT-PCR was coincident with immunocytochemistry. The myoblast-derived neurospheres expressed MAP-2 and GFAP after they were transplanted into the brain of rats with cerebral ischemia., Conclusion: Adult human myoblasts can be inducted to trans-differentiate into neural precursor cells.