Search

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.

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.)

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.)

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.)

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.)

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.

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.

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.

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.

We have developed an on-line sensing method for the detection of volatile organic compounds (VOCs) in contaminated aqueous solutions by combining a microporous hollow fiber membrane with an infrared (IR) sensing system. Polypropylene microporous hollow fibers were used to separate the VOCs from the aqueous solution into the hollow fibers, which were purged countercurrently for detection by the IR sensing systems. An evanescent-wave-type IR sensing system was used to detect the VOCs that were purged from the hollow fibers. The sensing element was coated with polyisobutylene (PIB) to concentrate the VOCs for their detection. To study the performance of this system, we examined a number of factors, such as the purging flow rate, the sample flow rate, and the volatilities of the VOCs. The results indicate that an increase in the purging flow rate reduces the analytical signal significantly, especially for purging flow rates >2 mL/min. The pumping flow rate for the aqueous sample also influenced the analytical signals, but far less sensitively. The volatilities of the examined compounds also affected the analytical signals: the higher the volatility of the compound, the lower the intensity of the analytical signals and the shorter the time required to reach the equilibrium signal. From an examination of the dynamic range of this proposed method, a regression coefficient >0.994 was obtained for concentrations below 250 mg/L, even under non-equilibrium conditions. The response time of the system was studied in an effort to examine the suitability of using this sensing method for automatic detection. The results indicate that new equilibrium conditions were established within 3 min for highly volatile compounds, which suggests that on-line monitoring of the levels of VOCs can be performed in the field.

Objective: To explore the expression of enhanced green fluorescent protein (EGFP) transduced into the brain via recombinant adeno-associated virus (rAAV) type 1 and rAAV type 2 vectors so as to select the better rAAV serotype and feasible gene transfer route to central nervous system (CNS)., Methods: Twenty-four SD male adult rats were randomly divided into 4 equal groups: rAAV1 intra-hippocampus injection group, rAAV1 intra-ventricular injection group, rAAV2 intra-hippocampus injection group, and rAAV2 intra-ventricular injection group to be injected stereotactically with titer and volume matched rAAV1-EGFP and rAAV2-EGFP vectors respectively. The rats were sacrificed respectively 2 and 4 weeks after injection and their brains were removed to be made into serial frozen coronal sections. Fluorescence microscopy was used to observe the expression of EGFP in the brain and to calculate the expression volume of EGFP in different parts of the brain., Results: Two weeks after injection EGFP was expressed in a small amount or not expressed in all groups. Four weeks after injection the EGFP expression volume were (7.00 +/- 0.98) mm(3) and (0.81 +/- 0.28) mm(3) in the rAAV1 and rAAV2 intra-hippocampus injection groups respectively (P < 0.01), and were (12.72 +/- 0.28) mm(3) and (0.24 +/- 0.13) mm(3) in the rAAV1 and rAAV2 intra-ventricular injection groups respectively (P < 0.001)., Conclusion: As gene-transducing vector in CNS rAAV1 is superior to rAAV2. High expression can be achieved by intra-ventricular injection with rAAV1 vectors.

Aim: To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST)., Methods: Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced., Results: Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%), and no mutation was found in benign tumors. The mutation rate showed significant difference (chi2=14.39, P<0.01) between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 malignant peripheral nerve sheath tumors, 2 intra-abdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas., Conclusion: C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.

The diffusiophoretic motion of a polyelectrolyte molecule or charged floc in an unbounded solution of a symmetrically charged electrolyte with a uniform prescribed concentration gradient is analytically studied. The model used for the particle is a porous sphere in which the density of the hydrodynamic frictional segments, and therefore also that of the fixed charges, is constant. The electrokinetic equations which govern the electrostatic potential profile, the ionic concentration distributions (or electrochemical potential energies), and the fluid velocity field inside and outside the porous particle are linearized by assuming that the system is only slightly distorted from equilibrium. Using a regular perturbation method, these linearized equations are solved for a charged porous sphere with the density of the fixed charges as the small perturbation parameter. An analytical expression for the diffusiophoretic mobility of the charged porous sphere in closed form is obtained from a balance between its electrostatic and hydrodynamic forces. This expression, which is correct to the second order of the fixed charge density of the particle, is valid for arbitrary values of kappaa and lambdaa, where kappa is the reciprocal of the Debye screening length, lambda is the reciprocal of the length characterizing the extent of flow penetration inside the particle, and a is the particle radius. Our result to the first order of the fixed charge density agrees with the corresponding solution for the electrophoretic mobility obtained in the literature. In general, the diffusiophoretic mobility of a porous particle becomes greater as the hindrance to the diffusive transport of the solute species inside the particle is more significant.

The steady diffusioosmotic and electroosmotic flows of an electrolyte solution in the fibrous porous medium constructed by a homogeneous array of parallel charged circular cylinders are analyzed under conditions of small Peclet and Reynolds numbers. The imposed electrolyte concentration gradient or electric field is constant and can be oriented arbitrarily with respect to the axes of the cylinders. The thickness of the electric double layers surrounding the cylinders is assumed to be small relative to the radius of the cylinders and to the gap width between two neighboring cylinders, but the polarization effect of the diffuse ions in the double layers is incorporated. Through the use of a unit cell model, the appropriate equations of conservation of the electrochemical potential energies of ionic species and the fluid momentum are solved for each cell, in which a cylinder is envisaged to be surrounded by a coaxial shell of the fluid. Analytical expressions for the diffusioosmotic and electroosmotic velocities of the bulk electrolyte solution as functions of the porosity of the ordered array of cylinders are obtained in closed form for various cases. Comparisons of the results of the cell model with different conditions at the outer boundary of the cell are made. In the limit of maximum porosity, these results can be interpreted as the diffusiophoretic and electrophoretic velocities of an isolated circular cylinder caused by the imposed electrolyte concentration gradient or electric field.

The diffusiophoresis in a homogeneous suspension of identical dielectric spheres with an arbitrary thickness of the electric double layers in a solution of a symmetrically charged electrolyte with a constant imposed concentration gradient is analytically studied. The effects of particle interactions (or particle volume fraction) are taken into account by employing a unit cell model, and the overlap of the double layers of adjacent particles is allowed. The electrokinetic equations that govern the ionic concentration distributions, the electrostatic potential profile, and the fluid flow field in the electrolyte solution surrounding the charged sphere in a unit cell are linearized assuming that the system is only slightly distorted from equilibrium. Using a perturbation method, these linearized equations are solved with the surface charge density (or zeta potential) of the particle as the small perturbation parameter. Analytical expressions for the diffusiophoretic velocity of the dielectric sphere in closed form correct to the second order of its surface charge density or zeta potential are obtained from a balance between its electrostatic and hydrodynamic forces. Comparisons of the results of the cell model with different conditions at the outer boundary of the cell are made.