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Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9‐dihydroxycoumestans via two‐electrode constant current electrolysis was developed. The application of a two‐phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o‐benzoquinone intermediates from over‐oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1‐targeted antitumor agent. [ABSTRACT FROM AUTHOR]

SUMMARY: Rhus chinensis Mill., an economically valuable Anacardiaceae species, is parasitized by the galling aphid Schlechtendalia chinensis, resulting in the formation of the Chinese gallnut (CG). Here, we report a chromosomal‐level genome assembly of R. chinensis, with a total size of 389.40 Mb and scaffold N50 of 23.02 Mb. Comparative genomic and transcriptome analysis revealed that the enhanced structure of CG and nutritional metabolism contribute to improving the adaptability of R. chinensis to S. chinensis by supporting CG and galling aphid growth. CG was observed to be abundant in hydrolysable tannins (HT), particularly gallotannin and its isomers. Tandem repeat clusters of dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) and serine carboxypeptidase‐like (SCPL) and their homologs involved in HT production were determined as specific to HT‐rich species. The functional differentiation of DQD/SDH tandem duplicate genes and the significant contraction in the phenylalanine ammonia‐lyase (PAL) gene family contributed to the accumulation of gallic acid and HT while minimizing the production of shikimic acid, flavonoids, and condensed tannins in CG. Furthermore, we identified one UDP glucosyltransferase (UGT84A), three carboxylesterase (CXE), and six SCPL genes from conserved tandem repeat clusters that are involved in gallotannin biosynthesis and hydrolysis in CG. We then constructed a regulatory network of these genes based on co‐expression and transcription factor motif analysis. Our findings provide a genomic resource for the exploration of the underlying mechanisms of plant‐galling insect interaction and highlight the importance of the functional divergence of tandem duplicate genes in the accumulation of secondary metabolites. [ABSTRACT FROM AUTHOR]

In previous studies, CST has been identified as having an immunostimulatory effect on Caenorhabditis elegans and macrophage of rats. Here, we further investigated its immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs). LPS‐stimulated PBMCs inflammatory model was established. Flow cytometry was applied to measure phagocytosis of PBMCs. Cytokine mRNA and protein expression levels of LPS‐stimulated PBMCs with or without CST were measured by qRT‐PCR and ELISA. The transcriptomic profile of CST‐treated PBMCs was investigated by RNA‐sequencing. Gene Ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) were applied to find potential signalling pathways. PBMCs showed a significant increase in phagocytic activity at 6 h after being incubated with CST at the concentration of 10 μg/mL. In the presence of LPS, CST maintained and promoted the expression of TNF‐α and chemokine CCL24. The content of pro‐inflammatory cytokines, such as IL‐1β, IL‐6 and IFN‐γ, which were released from LPS‐stimulated PBMCs, was reduced by CST at 6 h. Anti‐inflammatory cytokines, such as IL‐4, IL‐13 and TGF‐β1, were significantly increased by CST at 24 h. A total of 277 differentially expressed immune‐related genes (DEIRGs) were detected and cytokine‐cytokine receptor interaction was highly enriched. CST presented obvious anti‐inflammatory and immunoregulatory effects in LPS‐induced PBMCs inflammatory model not only by improving the ability of PBMCs to clear pathogens but also by decreasing pro‐inflammatory cytokines and increasing anti‐inflammatory cytokines. And the mechanism may be related to cytokine‐cytokine receptor interaction. [ABSTRACT FROM AUTHOR]

Non‐Negative Matrix Factorization (NMF) is a widely used dimension reduction method that factorizes a non‐negative data matrix into two lower dimensional non‐negative matrices: one is the basis or feature matrix which consists of the variables and the other is the coefficients matrix which is the projections of data points to the new basis. The features can be interpreted as sub‐structures of the data. The number of sub‐structures in the feature matrix is also called the rank. This parameter controls the model complexity and is the only tuning parameter for the NMF model. An appropriate rank will extract the key latent features while minimizing the noise from the original data. However due to the large amount of optimization error always present in the NMF computation, the rank selection has been a difficult problem. We develop a novel rank selection method based on hypothesis testing, using a deconvolved bootstrap distribution to assess the significance level accurately. Through simulations, we compare our method with a rank selection method based on hypothesis testing using bootstrap distribution without deconvolution and a method based on cross‐validation; we demonstrate that our method is not only accurate at estimating the true ranks for NMF, especially when the features are hard to distinguish, but also efficient at computation. When applied to real microbiome data (eg, OTU data and functional metagenomic data), our method also shows the ability to extract interpretable subcommunities in the data. [ABSTRACT FROM AUTHOR]

The generation and detection of circularly polarized light (CPL) are of importance in many modern technologies such as digital communications, machine vision, bio-imaging, and 3D displays. In this study, inspired by the fact that various species of plants and animals can efficiently produce and/or perceive CPL with chiral photonic crystal structures, efforts are made to fabricate luminescent chiral photonic crystals with caesium lead halide perovskites, a class of solution-processable semiconductors that have excellent luminescence properties and readily tunable electronic band gaps. Coupling between the emission frequency of the perovskite and the cavity resonance frequency of the photonic crystal structure can be established at any desired point in the visible region, giving rise to CPL output with a dissymmetry factor up to −0.34. These results suggest a new approach to chiral light-emitting materials and may contribute to the development of semiconductors with ordered microstructures. [ABSTRACT FROM AUTHOR]

Phenothiazinone is a promising yet underutilized fluorophore, possibly due to the lack of a general accessibility. This study reports a robust and scalable TEMPO‐mediated electrochemical method to access a variety of phenothiazinones from 2‐aminothiophenols and quinones. The electrosynthesis proceeds in a simple cell architecture under mild condition, and notably carbon–halogen bond in quinones remains compared to conventional methods, enabling orthogonal downstream functionalization. Mechanistic studies corroborate that TEMPO exerts a protective effect in avoiding product decomposition at the cathode. In particular, benzophenothiazinones show intriguing luminescence in both solid and solution state, and thus their photophysical properties are scrutinized in detail. Further bio‐imaging of the lipid droplets in living cells highlights the considerable promise of benzophenothiazinones as fluorescent dye in the biomedical fields. [ABSTRACT FROM AUTHOR]

The ever‐increasing demand for data storage and neuromorphic computing calls for innovative, high‐density solutions, such as resistive random‐access memory (RRAM). However, the integration of resistive switching and rectification at the nanoscale remains a formidable challenge. In this study, we introduce a bistable [2]catenane‐based supramolecular junction that simultaneously functions as a resistive switch and a diode. All supramolecular junctions are highly stable and reproducible over thousands of resistive switching cycles, because the nano‐confinement of two mechanically interlocked rings can stabilize the radical states of pyridinium moieties under ambient conditions. The successful realization of supramolecular junctions in functionality with a thickness of approximately 2 nm presents a promising avenue for the development of molecule‐scale based RRAM for a better solution to high density and energy efficiency. [ABSTRACT FROM AUTHOR]

Objectives: The mechanisms of regional acceleratory phenomenon (RAP) induced by orthognathic osteotomy are unclear. It was not known if locally hypoxic microenvironment changes were involved in this phenomenon. Methods: Hypoxia‐induced factor‐1α knockout mice harboring Cathepsin K (CTSK) Cre were used to investigate the effect of hypoxia‐driven osteoclasts on alveolar bone remodeling. RAW264.7 cells were induced by CoCl2 to observe the effects of dendritic cell‐specific transmembrane protein (DC‐STAMP) on the fusion and differentiation of osteoclasts. Results: We found mandibular osteotomy of C57 mice induced active alveolar osteoclasts and increased hypoxia‐induced factor‐1α (HIF‐1α) positive staining areas. Alveolar bone density of the 10‐week‐old HIF‐1α conditional knockout (CKO) mouse was increased at 10 and 14 days after bilateral mandibular osteotomy. Moreover, decreased numbers of osteoclasts and matrix metalloproteinase 9 (MMP‐9)‐positive cells were observed on the surface of bone resorption lacunae in the CKO group. HIF‐1α could increase the expression level of DC‐STAMP to enhance osteoclastogenesis and cell fusion in active RAW264.7 cells. Conclusion: Our data considered hypoxia‐driven osteoclasts resorption to be an adaptive mechanism to permit alveolar bone loss after bilateral mandibular osteotomy of mice. [ABSTRACT FROM AUTHOR]

Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC50 value of 8.16 ± 0.47 μM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model. [ABSTRACT FROM AUTHOR]

Density functional theory calculations have been utilized to investigate the synergistic effect of palladium(0) and copper(I) catalyzed selective formation of allylated indole from (2‐alkynyl)‐phenylisocyanate and allyl methyl carbonate. The main competing reaction yielding the N‐allyl carbamate was also considered. Calculated results indicate that using the Pd(0)‐complex alone, the generation of indole is kinetically much less favored than producing the N‐allyl carbamate compound. However, the co‐addition of Cu(I) catalyst can considerably decrease the barrier for the intramolecular cyclization step, leading to the formation of the indole product. Analysis of the cyclization process suggests that Cu(I) complex can act as a Lewis acid to activate the linear alkyne group via a π‐coordination manner prior to the formation of a 5‐membered ring transition state toward indole formation. Altogether, the mechanistic insights revealed in the present study aim at a better understanding of the mechanism and the factors governing the selectivity in synergistic Pd/Cu catalysis. [ABSTRACT FROM AUTHOR]

SHR4640, also named as ruzinurad, is a selective human urate transporter 1 (URAT1) inhibitor developed for the treatment of hyperuricemia and gout. This study evaluated the high‐fat, high‐calorie food effect on the pharmacokinetics and pharmacodynamics of SHR4640 in healthy Chinese male volunteers. In this open‐label, randomized, 2‐period crossover phase 1 trial, 14 healthy male subjects were randomized to receive a single 10‐mg dose of SHR4640 under both fasted and fed conditions. The washout period was 7 days. Blood samples were collected for pharmacokinetic and pharmacodynamic analysis. Pharmacokinetic parameters were analyzed by a noncompartmental method. The safety of the drug was also evaluated in the trial. A total of 14 healthy male volunteers were enrolled in the study, and finally 13 healthy volunteers completed the study. A single 10‐mg dose of SHR4640 was safe and well tolerated in healthy Chinese male volunteers. After single‐dose administration of SHR4640, the 90%CIs of the geometric mean ratios of the area under the plasma concentration–time curve from time 0 to the last quantifiable concentration and the area under the plasma concentration–time curve from time 0 to infinity were within the equivalence criteria of 0.80‐1.25. The 90%CIs of maximum plasma concentration was slightly outside the lower limit of bioequivalent criteria, with about 13.40% decrease in the fed versus fasted condition. The time to maximum concentration was slightly delayed under the fasted condition. A single 10‐mg dose of SHR4640 was safe and well tolerated in this trial. The main pharmacokinetic parameters and serum uric acid lowering of SHR4640 were not affected by food effect; thus, SHR4640 can be recommended to be administered with or without food [ABSTRACT FROM AUTHOR]

Summary: Wheat is a globally vital crop, but its limited genetic variation creates a challenge for breeders aiming to maintain or accelerate agricultural improvements over time. Introducing novel genes and alleles from wheat's wild relatives into the wheat breeding pool via introgression lines is an important component of overcoming this low variation but is constrained by poor genomic resolution and limited understanding of the genomic impact of introgression breeding programmes. By sequencing 17 hexaploid wheat/Ambylopyrum muticum introgression lines and the parent lines, we have precisely pinpointed the borders of introgressed segments, most of which occur within genes. We report a genome assembly and annotation of Am. muticum that has facilitated the identification of Am. muticum resistance genes commonly introgressed in lines resistant to stripe rust. Our analysis has identified an abundance of structural disruption and homoeologous pairing across the introgression lines, likely caused by the suppressed Ph1 locus. mRNAseq analysis of six of these introgression lines revealed that novel introgressed genes are rarely expressed and those that directly replace a wheat orthologue have a tendency towards downregulation, with no discernible compensation in the expression of homoeologous copies. This study explores the genomic impact of introgression breeding and provides a schematic that can be followed to characterize introgression lines and identify segments and candidate genes underlying the phenotype. This will facilitate more effective utilization of introgression pre‐breeding material in wheat breeding programmes. [ABSTRACT FROM AUTHOR]

The study aimed to examine the indirect factors underlying the association between work–family conflict and posttraumatic stress symptoms (PTSS) in college teachers during the COVID‐19 pandemic. Three potential indirect factors were examined: perceived stress, basic psychological needs, and rumination. A total of 274 college teachers were recruited. All participants completed an electronic questionnaire that assessed their exposure to the pandemic, work–family conflict, perceived stress, basic psychological needs, rumination, and PTSS. The results showed that after controlling for pandemic exposure, gender, and age, work–family conflict was associated with PTSS via perceived stress alone, rumination alone, a path from perceived stress to basic psychological needs, and a path from perceived stress to rumination. These results indicate that work–family conflict is positively associated with PTSS indirectly via perceived stress, rumination, and basic psychological needs during the COVID‐19 pandemic. These three mediators may completely explain the relation of work–family conflict to PTSS. [ABSTRACT FROM AUTHOR]

The antibiotic‐resistant Klebsiella pneumoniae (Kp) has become a significant crisis in treating pneumonia. Low‐frequency ultrasound (LFU) is promising to overcome the obstacles. Mice were infected with bioluminescent Kp Xen39 by intratracheal injection to study the therapeutic effect of LFU in combination with antibiotics. The counts per second (CPS) were assessed with an animal biophoton imaging system. Bacterial clearance, histopathology, and the concentrations of cytokines were determined to evaluate the therapeutic effect. LC–MS/MS was used to detect the distribution of antibiotics in the lung and plasma. LFU in combination with meropenem (MEM) or amikacin (AMK) significantly improved the behavioural state of mice. The CPS of the LFU combination group were more significantly decreased compared with those of the antibiotic alone groups. The average colony‐forming units of lung tissue in the LFU combination groups were also lower than those of the antibiotic groups. Although no significant changes of cytokines (IL‐6 and TNF‐α) in plasma and bronchoalveolar lavage fluid were observed, LFU in combination with antibiotics showed less inflammatory damage from histopathological results compared with the antibiotic‐alone groups. Moreover, 10 min of LFU treatment promoted the distribution of MEM and AMK in mouse lung tissue at 60 and 30 min, respectively, after dosage. LFU could enhance the effectiveness of MEM and AMK in the treatment of Kp‐induced pneumonia, which might be attributed to the fact that LFU could promote the distribution of antibiotics in lung tissue and reduce inflammatory injury. [ABSTRACT FROM AUTHOR]

Youkenafil hydrochloride is a novel selective phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction. Its safety, tolerability, and pharmacokinetics were evaluated in healthy Chinese male volunteers. In addition, this study explored the effect of food on the pharmacokinetic parameters of youkenafil hydrochloride. The study was divided into 3 trials: a single ascending dose (25, 50, 100, 150, or 200 mg youkenafil), multiple dose (50, 100, or 150 mg youkenafil once daily for 7 consecutive days), and food effect (50 mg youkenafil single dose). The overall tolerability of youkenafil was good. Youkenafil was rapidly absorbed after a single oral dose. Food intake impeded absorption efficiency but had no significant effect on area under the plasma concentration–time curve values. The mean accumulation ratio in area under the plasma concentration–time curve and maximum plasma concentration ranged from 1.3 to 1.6 and from 1.2 to 1.4 after once‐daily dosing. There was no apparent accumulation following consecutive administration for 7 days. Less than 1% of the dose was found in urine as the intact drug for all dose groups. Single‐dose youkenafil up to 200 mg and multiple doses up to 150 mg were generally safe and well tolerated. [ABSTRACT FROM AUTHOR]

Delayed platelet engraftment (DPE) is associated with poor survival and increased transplantation‐related mortality after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Therefore, treatments are needed to improve platelet engraftment and prevent DPE. We performed a phase three, non‐inferior, randomized controlled study of eltrombopag or recombinant human thrombopoietin (rhTPO) to promot platelet engraftment after allo‐HSCT. Candidates for allo‐HSCT were randomly assigned to receive oral eltrombopag (50 mg daily) or subcutaneous rhTPO (15000U daily) from the first‐day post‐transplantation. The primary endpoint was the cumulative numbers of platelet engraftment (platelet recovery ≥20 × 109/L, without transfusion, for seven consecutive days) on day 60 after transplantation. We performed intention‐to‐treat analyses with a non‐inferior margin of −15%. A total of 92 participants underwent randomization. 44 and 48 patients were randomized to the eltrombopag and rhTPO groups, respectively. The median duration of follow‐up was 360 days (range: 12–960 days). The cumulative incidence of platelet engraftment on day 60 after transplantation in eltrombopag group was 86.4% (38/44) compared with 85.4% (41/48) in the rhTPO group (absolute risk difference [ARD] 1%, one‐sided lower limit of 95% confidence interval [CI] −13.28%, Pnon‐inferirioty = 0.014). The rate of DPE in the eltrombopag group was 6.8% (3/44) compared with 12.5% (6/48) in the rhTPO group (ARD ‐5.7%, one‐sided higher limit of 95% CI 6.28%, Pnon‐inferirioty = 0.063). Approximately, three‐fourths of non‐hematologic adverse events were not observed in the eltrombopag group but three patients (3/48, 6%) experienecd them in the rhTPO group. In addition, platelet transfusions unite from day 0 to day 21, or from day 22 to day 60, progression‐free survival, overall survival were not significantly different between both groups. Eltrombopag was non‐inferior to rhTPO in promoting platelet engraftment post allo‐HSCT for patients with hematological malignancy. Oral eltrombopag was more convenient for patients than subcutaneous rhTPO (NCT03515096). [ABSTRACT FROM AUTHOR]

An edible polysaccharide film with high tensile strength and biodegradability was prepared by freeze–thaw treatment with sodium alginate (SA) and hyaluronic acid (HA) and cross‐linking with calcium lactate. The SA/HA ratio, the calcium concentration, the number of freeze–thaw cycles, and the calcification time all have significant effects on the tensile strength of SA/HA films. An increase in tensile strength was obtained due to the reaction of 3% calcium lactate with 60% SA. Compared with the control group, the tensile strength of the SA/HA films developed in this study increased by 214% from 3.188 to 10.02 MPa. The compatibility of films was evaluated by Fourier transform infrared spectroscopy; the absorption peaks of SA and sodium hyaluronate had shifted to a wavelength of 3,403 ~ 3,411 cm−1 after freeze–thaw treatment, and a strong interaction occurred at a wavelength of 1,328 cm−1. In addition, the swelling and solubility of the SA/HA film decreased by half during the freeze–thaw period. Further, scanning electron microscopy showed that the cross sections of the films were uniform and compact after two freeze–thaw treatments. SA/HA films that exhibited increased tensile strength and that had the potential to overcome the poor water vapor barrier problems traditionally experienced with these films were developed in this study. [ABSTRACT FROM AUTHOR]

Polyploidization and hybridization are very common in natural plant species, and mixed‐ploidy species provide a unique opportunity to study the effects of evolutionary history, local abundance, and ploidy level on the direction and extent of introgression between intraspecific lineages. First, we delimited two morphologically cryptic lineages of Phragmites australis Trin. ex Steud. in temperate China using 11 nuclear microsatellites and two chloroplast DNA fragments with 225 samples from China as well as 11 samples from Oceania and Europe. Our evidence supported that haplotype O and haplotype P were two relatively independent lineages with low and high ploidy levels, respectively; haplotype M might be ancient and could have undergone a complex evolutionary history. Then we examined the lineage divergence and compared the introgression patterns between two major lineages along geographical and abundance gradients with a large number of samples (n = 1067) collected from China. The sympatric coexistence of two lineages in north and northeast China implies an ongoing or potential introgression between them. Cline analysis showed that the level of genetic admixture were significantly correlated with longitude rather than latitude. Our results also suggested that ploidy level could deeply influence the introgression asymmetry, and the effect of the current local abundance on introgression might be covered by the past coexistence time driven by phylogeographic history. Our study draws a baseline for future research on the ecological and evolutionary consequences of migration and introgression of Chinese P. australis under global change. [ABSTRACT FROM AUTHOR]

A highly efficient and eco‐friendly method for the tetramethylammonium iodide‐mediated sulfenylation/annulation of enaminones using thiosulfonates as the sulfenyl source was described under open‐air, metal‐, and oxidant‐free conditions. This method provides an alternative way of constructing C−S bonds, affords various substituted sulfenylated chromones in moderate to good yields, and shows broad substrate scope, and good functional group tolerance. [ABSTRACT FROM AUTHOR]

Genistein, a soy derived isoflavanoid compound, exerts anticancer effects in various cancers. Nasopharyngeal cancer stem cells (NCSCs) are a small subpopulation of cancer cells which are responsible for initiation, progression, metastasis, and recurrence of nasopharyngeal cancer. The present study aimed to investigate the suppressive effects of genistein on NCSCs and its underlying mechanism. NCSCs were enriched from human nasopharyngeal cancer cell lines CNE2 and HONE1 through tumorsphere-forming assay. It was shown that genistein inhibited the tumorsphere formation capacity, decreased the number of EpCAM+ cells, downregulated the expression of NCSCs markers, suppressed cell proliferation, and induced apoptosis of NCSCs. Genistein suppressed the activity of Sonic hedgehog (SHH) signaling, which was important for the maintenance of NCSCs, while activation of SHH signaling by purmorphamine diminished the inhibitory effects of genistein on NCSCs. Our data suggested that genistein inhibited NCSCs through the suppression of SHH signaling. These findings support the use of genistein for targeting NCSCs. [ABSTRACT FROM AUTHOR]

Summary: Internet of things (IoT) botnets such as Mirai are rampant in the past years. Port scanning is a well‐known behavior of botnets for searching targets in networks. To detect port scanning, a detector requires network statistics with high discriminatory power. In P4‐based software‐defined network (SDN), switches take charge of recording characteristics about scanning behaviors, and controllers pull the statistics from the switches periodically for anomaly detection. Given storage resources in switches are limited, we proposed a scanner data collection method, 0‐Replacement, in P4‐based SDN to efficiently collect scanner data and improve the detection rate. 0‐Replacement, however, does not consider performance degradation caused by the hash collision. In this paper, we combine the conception of Hashpipe with 0‐Replacement and propose a new scanner data collection method named E‐Replacement. By leveraging the conception of Hashpipe, E‐Replacement can mitigate the performance degradation caused by the hash collision. Through simulations, we show that E‐Replacement improves the detection rate by up to 6.73% and 210.82% compared to 0‐Replacement and the traditional sample and hold method, respectively. Besides, E‐Replacement improves the precision by around 528.2% compared to the count‐min sketch and k‐ary sketch methods. The memory usage in E‐Replacement is the same as 0‐Replacement. In simulations, E‐Replacement can detect around 93.4% of scanners in a class B network with only 4.02‐Mb SRAM. After implementing E‐Replacement on a software P4 switch, BMv2, we observe the extra forwarding latency for E‐Replacement is not greater than a millisecond. [ABSTRACT FROM AUTHOR]

Cardiotoxicity has been one of the most common causes of withdrawal of drugs from the market, and prolongation of the QT interval is one of the manifestations of drug cardiotoxicity. Iptakalim hydrochloride (ITKL) is a selective ATP‐sensitive potassium channel opener used to treat hypertension. It is crucial to assess the risk of cardiac repolarization of ITKL in clinical trials. This study was conducted to determine the effect of ITKL on corrected QT (QTc) interval. A randomized, double‐blind, placebo‐controlled single‐ and multidose regimen was carried out to investigate the QTc and ITKL concentration correlation. ITKL was administered at doses of 5, 10, 15, and 20 mg with single oral administration and 10 and 20 mg with multiple oral administration, along with placebo, in 83 healthy subjects. Electrocardiograms (ECGs) and blood samples were collected on a preset time schedule. A ΔΔQTcF effect above 10 milliseconds was excluded at all observed plasma levels. Among them, the highest dose was 20 mg, which is twice the therapeutic dose. We concluded that ITKL did not prolong the QT interval in healthy subjects within the therapeutic dose. Retrospectively registered: The study was registered at Chinese Clinical Trial Registry with registration number ChiCTR1800014466. [ABSTRACT FROM AUTHOR]

S100 calcium binding protein P (S100P) and miR‐495 are aberrantly expressed and exert essential roles in cancers. However, the mechanisms of miR‐495‐S100P in pancreatic cancer are yet to be illustrated. Thus, we explored the regulatory functions of miR‐495‐S100P axis in pancreatic adenocarcinoma cells growth and invasion. In this study, we identified that S100P was upregulated in pancreatic adenocarcinoma by bioinformatics analysis of the GEO (Gene Expression Omnibus database) microarray dataset (GSE16515). Western blotting and luciferase reporter gene analysis exhibited that miR‐495 negatively determined the level of S100P via binging to its 3′‐untranslated regions (3′‐UTRs). A series of functional experiments indicated that upregulation of miR‐495 or S100P knockdown suppressed pancreatic adenocarcinoma cells proliferation, invasion, and promoted apoptosis. Furthermore, the expression of S100P was negatively associated with the level of miR‐495 in The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma case‐cohort. Besides, reintroduction of S100P debilitated the anti‐cancer action of miR‐495 in pancreatic adenocarcinoma cells. Our data indicated that miR‐495 performed suppressive roles in pancreatic adenocarcinoma through targeting S100P. [ABSTRACT FROM AUTHOR]

Assembly of functional superstructure microparticles into large‐scale transferable ensembles is a practical approach to elaborate collective properties for catalytic and sensing applications. Here, a two‐step assembly process is proposed to fabricate a mosaic‐like highly oriented monolayer consisting of densely packed CuI superstructure microparticles (s‐CuI) over a large area. First, optimized synthesis and Cl doping of rectangular sheet‐like s‐CuI is achieved by antisolvent crystallization. Then, a steep capillary gradient is created along the water surface to compress the pre‐dispersed s‐CuI into a centimeter‐sized mosaic‐like highly oriented monolayer, which can be integrally transferred onto fluorine‐doped tin oxide glass substrates. The s‐CuI monolayer with optimal Cl doping exhibits a highly sensitive electrochemical response to glucose in a nonenzymatic weakly alkaline environment. A photoelectrochemical response to glucose can also be achieved in nonenzymatic neutral solution. The high performances are ascribed to large surface area, excellent electrical contact, and consistently exposed Cu+ active sites of the s‐CuI building blocks. [ABSTRACT FROM AUTHOR]

Flurbiprofen is a non‐steroidal anti‐inflammatory drug. We evaluated the bioequivalence of a new formulation of flurbiprofen axetil for injection and the reference drug ROPION (another kind of flurbiprofen axetil injection marketed for use) in healthy Chinese subjects. This is a single‐centre, randomized, open‐label, single‐dose, two period crossover bioequivalence study. Each subject received a single intravenous injection at the dose of 50 mg under fasting. The drug was dissolved in 100 mL normal saline, and the injection was completed in 15 minutes. There was a 7‐day washout period between the two administrations. The plasma concentrations of flurbiprofen were measured by LC‐MS/MS, and descriptive statistics were used to describe the safety outcomes including adverse events (AEs) and adverse drug reactions (ADRs). Twenty‐four subjects were enrolled in this study. Mean values of primary PK parameters (Tmax, Cmax, AUC0‐t, AUC0‐∞, λz, T1/2) were similar (P > 0.05). Tmax for both products is 0.3 hours. The 90% confidence intervals (CIs) for peak concentration Cmax ranged between 96.87% and 100.42%, and the area under curve AUC0‐t and AUC0‐∞ ranged between 99.09% and 104.29% and 98.97% and 104.29%, respectively. The 90% CIs for the geometric means and ratios of primary PK endpoints of flurbiprofen axetil injection to reference drug ranged between 98.97% and 104.29%. The adverse event rate of the test product was 8.3% and no serious adverse events (SAE) occurred in this clinical study. We concluded that the test product and the reference drug were bioequivalent and the safety was high in healthy Chinese subjects. [ABSTRACT FROM AUTHOR]

Simple sequence repeat (SSR) markers play an important role in genetic and molecular breeding programs, especially for non‐model species. We identified SSRs from expressed sequence tags (EST‐SSRs) and whole genome sequences (gSSRs), by analysing the transcriptome and genome of the Mongolian sea buckthorn (Hippophae rhamnoides subsp. mongolica) cultivar 'Sunny'. Using the same number of loci, EST‐SSRs showed higher transferability to Hippophae than gSSRs, and phylogenetic trees based on EST‐SSRs demonstrated higher resolution for classifying Hippophae species and subspecies into clades, possibly due to high conservatism and/or existence of adaptive divergence between species/subspecies in coding sequence regions. In contrast, parentage analyses showed that gSSRs were more effective at resolving parentage than EST‐SSRs due to higher level of polymorphism in gSSRs. The markers developed in this study can be used in the identification and pedigree reconstruction of species/subspecies of sea buckthorn, while their usage in clarifying phylogenetic relationship among species remains to be discussed. The comparison between EST‐SSRs and gSSRs would provide insight into the trade‐off between differentiation and polymorphism in marker selection for breeding programs. [ABSTRACT FROM AUTHOR]

A simple, efficient, and green method for the iodine‐promoted regioselective C‐4 sulfenylation of isoquinolin‐1(2H)‐ones using commercially available aryl sulfonyl chlorides as the sulfur source was described under metal‐ and solvent‐free conditions. The reaction proceeded smoothly under simple conditions to obtain 4‐arylthioisoquinolin‐1(2H)‐ones in moderate to good yields, and showed high regioselectivity, broad substrate scope, and good functional group tolerance. A radical reaction mechanism involving ArS. radicals as key intermediates is proposed for the present transformation. [ABSTRACT FROM AUTHOR]

Background and Aim: Single‐nucleotide polymorphisms (SNPs) in long non‐coding RNAs (lncRNAs) are potential biomarkers for cancer risk, but their association with hepatocellular carcinoma (HCC) is unclear. We examined the association of lncRNA‐related SNPs with HCC susceptibility and explored the optimal genetic models for SNPs. Methods: Five candidate SNPs linked with digestive tumors were first genotyped in a screening population of 700 HCC and 2800 control cases. The association between each SNP and HCC risk was estimated by multivariate logistic regression adjusted by sex and age and recorded as odds ratio (OR) with 95% confidence interval. Significant associations were further tested in a validation population with 1140 HCC and 5115 control cases. Finally, the most appropriate genetic models for HCC‐associated SNPs were identified using pairwise allele differences; the overall gene effects of each SNP were further evaluated based on optimal genetic models. Results: Three candidate SNPs, rs7315438, rs6983267, and rs10795668, showed statistical connections with HCC risk in the discovery stage. Among these, rs7315438 remained steadily significant in the validation stage; rs7315438 and rs10795668 both reached statistical threshold in the combined analysis of both stages. SNP rs7315438 (TC vs TT/CC, OR = 1.410, P < 0.001) was associated with increased risk of HCC in a complete overdominant model, whereas rs10795668 (AG vs AA/GG, OR = 0.892, P = 0.035) exerted a protective effect on HCC risk in a complete overdominant model. Conclusions: Long non‐coding RNA‐related SNPs rs7315438 and rs10795668 are potential biomarkers for HCC susceptibility, especially when evaluated based on their optimal genetic models. [ABSTRACT FROM AUTHOR]

Imine synthesis has enjoyed a long history as the dynamic covalent reaction of choice for the construction of purely covalent molecular architectures. In organic solvents, the formation of imine bonds is reversible but leads to thermodynamically stable products. In the presence of water, however, imine bonds are labile, a fact which limits their utility as mediators of self‐assembly in aqueous and biological media. In this Review, we discuss water‐compatible dynamic covalent bonds based on N‐substituted imine derivatives, namely hydrazones and oximes, for the self‐assembly of metal‐free organic architectures with well‐defined structures. The reasons why hydrazones and oximes are more robust in water than their parent imines are explained. Recent progress in the self‐assembly, characterization, and design principles of a variety of complex molecules including macrocycles, cages, catenanes, and knots in aqueous media is highlighted. Emerging applications for these molecules, including guest recognition and separations, are also discussed. [ABSTRACT FROM AUTHOR]

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Purpose: To identify how Epstein‐Barr virus (EBV) status combined with molecular profiling predicts the prognosis of gastric cancer patients and their associated clinical actionable biomarkers. Experimental Design: A next‐generation sequencing assay targeting 295 cancer‐related genes was performed in 73 EBV‐associated gastric cancer (EBVaGC) and 75 EBV‐negative gastric cancer (EBVnGC) specimens and these results were compared with overall survival (OS). Results: PIK3CA, ARID1A, SMAD4, and PIK3R1 mutated significantly more frequently in EBVaGC compared with their corresponding mutation rate in EBVnGC. As the most frequently mutated gene in EBVnGC (62.7%), TP53 also displayed a mutation rate of 15.1% in EBVaGC. PIK3R1 was revealed as a novel mutated gene (11.0%) associated almost exclusively with EBVaGC. PIK3CA, SMAD4, PIK3R1, and BCOR were revealed to be unique driver genes in EBVaGC. ARID1A displayed a significantly large proportion of inactivated variants in EBVaGC. A notable finding was that integrating the EBV status with tumor mutation burden (TMB) and large genomic instability (LGI) categorized the tumors into four distinct molecular subtypes and optimally predicted patient prognosis. The corresponding median OSs for the EBV+/TMB‐high, EBV+/TMB‐low, EBV‐/LGI‐, and EBV‐/LGI+ subtypes were 96.2, 75.3, 44.4, and 20.2 months, respectively. The different subtypes were significantly segregated according to distinct mutational profiles and pathways. Conclusions: Novel mutations in PIK3R1 and TP53 genes, driver genes such as PIK3CA, SMAD4, PIK3R1, BCOR, and ARID1A, and distinguished genomic profiles from EBVnGC were identified in EBVaGC tumors. The classification of gastric cancer by EBV, TMB, and LGI could be a good prognostic indicator, and provides distinguishing, targetable markers for treatment. [ABSTRACT FROM AUTHOR]

While hundreds of consistently altered metabolic genes had been identified in hepatocellular carcinoma (HCC), the prognostic role of them remains to be further elucidated. Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas—Liver Hepatocellular Carcinoma and GSE14520 data set from the Gene Expression Omnibus database. Univariate Cox regression analysis and lasso Cox regression model established a novel four‐gene metabolic signature (including acetyl‐CoA acetyltransferase 1, glutamic‐oxaloacetic transaminase 2, phosphatidylserine synthase 2, and uridine‐cytidine kinase 2) for HCC prognosis prediction. Patients in the high‐risk group shown significantly poorer survival than patients in the low‐risk group. The signature was significantly correlated with other negative prognostic factors such as higher α‐fetoprotein. The signature was found to be an independent prognostic factor for HCC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. Furthermore, gene set enrichment analyses revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four‐gene metabolic signature for HCC prognosis prediction. The signature might reflect the dysregulated metabolic microenvironment and provided potential biomarkers for metabolic therapy and treatment response prediction in HCC. [ABSTRACT FROM AUTHOR]

Background: Gene mutations may play an important role in the development, response to treatment and prognosis of colorectal cancer (CRC). This retrospective study aimed to investigate the mutation profiling of Chinese patients with CRC, and its correlation with clinicopathological features and prognosis. Methods: This study included 1190 Chinese CRC patients who were diagnosed between May 1998 and December 2018 and received clinical genetic testing. The OncoCarta Panel was used to test a total of 238 possible mutations in 19 common oncogenes. Results: Five hundred and eighty‐two (48.9%) cases were detected with gene mutations. Of the 582 cases, there were 111 cases (19.7%) with two concurrent mutations, and six cases (1.0%) with three concurrent mutations. KRAS was the most common gene mutation that occurred in all cases (429, 36.1%), followed by PIK3CA (121, 10.2%), NRAS (47, 3.9%), BRAF (35, 2.9%), HRAS (11, 0.9%) and epidermal growth factor receptor (EGFR) (11, 0.9%). AKT1, KIT, FGFR1, FGFR3, FLT3, CDK, ERBB2, ABL1, MET, RET and PDGFRA mutations were also detected in several cases. When it came to prognosis, we found that KRAS/NRAS/PIK3CA/BRAF mutation was not associated with prognosis. But BRAF mutation was associated with poor prognosis in patients who accepted anti‐EGFR therapy. Conclusions: The molecular testing offered the clinical data and mutation profile of Chinese CRC patients. The information of these mutated genes may help to find out the correlation between mutated genes and the development or prognosis of CRC. [ABSTRACT FROM AUTHOR]

Oxime condensation as well as template-directed synthesis based on radical-pairing interactions were used in the synthesis of an octacationic [2]catenane in 20% yield. The [2]catenane consists of two identical mechanically interlocked tetracationic macrocyclic components. Each of the ring components contains two dicationic bipyridinium (BIPY2+) functions. The structure of the [2]catenane was fully characterized by NMR spectroscopy, mass spectrometry, as well as X-ray crystallography. In the oxidized state, the [2]catenane exists in a co-conformation where its four BIPY2+ units are located as far as possible from each other. Upon reduction of BIPY2+ into the radical state, namely BIPY+*, we propose that the [2]catenane undergoes mechanical movement, driven by radical pairing interactions between these radical building blocks. The redox-stimulated switching behavior of this [2]catenane was confirmed by electrochemistry, UV-Vis-NIR absorption spectroscopy, and 1H NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV)‐associated gastric carcinomas (EBVaGCs) may account for 8–9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV‐DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat‐sen University Cancer Center for EBER examination. We detected EBV‐DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV‐DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV‐negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3‐year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV‐DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV‐DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV‐DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients. What's new? Epstein–Barr Virus (EBV)‐associated gastric carcinomas (EBVaGC) may account for 8–9% of all gastric cancers (GC). The exact role of EBV status in predicting the prognosis of GC remains to be clarified, however. Here, the authors report a prevalence of EBVaGC in GC in China of 5.1%, as defined by EBER staining in cancerous tissue. EBVaGC patients had a better overall survival than EBV‐negative patients. Though only half of EBVaGC patients gained detectable plasma EBV‐DNA levels, elevated plasma EBV‐DNA predicted relapse and poor response to chemotherapy. Dynamic detection of plasma EBV‐DNA load may offer an easily accessible biomarker to monitor EBVaGC. [ABSTRACT FROM AUTHOR]

Objective: Fracture is a common consequence of osteoporosis and is associated with high morbidity and mortality. Recently, increasing evidence has suggested that polymorphisms in tumor necrosis factor‐α (TNF‐α) gene were associated with osteoporosis risk and bone mineral density (BMD), but results remain conflicting. We herein performed a meta‐analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. Methods: The PubMed, EMBASE, Cochrane Library, CNKI (China National Knowledge Infrastructure) and Wan Fang databases were searched for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed and all available data were accumulated. The pooled odds ratios (ORs) or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the relationships. Results: A total of 15 studies involving 5273 subjects were included in our meta‐analysis. The GG genotype of TNF‐α G308A was associated with an increased risk of osteoporosis under a mutant model (GG vs GA+AA: OR = 0.63, 95% CI: 0.51‐0.77, P < 0.0001, I2 = 31%). Additionally, we also observed a significant association between G308A polymorphism and BMD of lumbar spine (AA vs GG: P = 0.01, I2 = 53%). However, TNF‐α T1031C, C857T and C863A polymorphisms had no obvious impacts on osteoporosis risk. Conclusions: The present meta‐analysis demonstrated that TNF‐α G308A polymorphism may act as a potential candidate biomarker for screening, diagnosis, and treatment of osteoporosis, which will help improve individualized therapy of osteoporosis patients in clinics. [ABSTRACT FROM AUTHOR]

The rapid bone remodeling after osteotomy has been reported for a long time. However, the underlying mechanism promoting the active bone reconstruction was still to be elucidated. Since not only the bone, blood vessels, and supportive tissues, but also the local microenvironment were destroyed, if the changes on the cell metabolism was contributed to the accelerated bone remodeling came into sight. In present study, we found that the mandibular osteotomy in rabbit activated osteoclasts, as well as the expression of hypoxia‐inducible factor 1α (HIF‐1α) in alveolar bone. Hypoxia or HIF‐1α could enhanced osteoclastogenesis, bone absorption, and lactic acid concentration in receptor activator of nuclear factor κΒ ligand‐induced RAW264.7 cells. Coincided with the upregulated HIF‐1α expression, HIF‐driven glycolytic enzymes, such as lactate dehydrogenase A (LDHA), glucokinase (GCK), pyruvate kinase M2 (PKM2), and phosphofructokinase1 (PFK1), were found massively increased in both hypoxic RAW264.7 cells and the alveolar HIF‐1α‐positive osteoclasts after mandibular osteotomy. Knockdown of HIF‐1α suppressed not only the hypoxia‐mediated glycolysis, but also the hypoxia‐induced acid secretion and bone resorption in RAW264.7 cells. Application of inhibitor on glycolysis gave rise to the similar results as HIF‐1α knockdown. Our findings suggested that hypoxia‐driven glycolysis in osteoclasts was an adaptive mechanism to permit alveolar bone remodeling after mandibular osteotomy. The rapid bone remodeling after osteotomy has been reported for a long time. However, the underlying mechanism promoting the active bone reconstruction was still to be elucidated. Hypoxia‐driven glycolysis in osteoclasts was an adaptive mechanism to permit alveolar bone remodeling after mandibular osteotomy. [ABSTRACT FROM AUTHOR]

A novel, rapid and sensitive chemiluminescence (CL) method for the determination of oxytetracycline hydrochloride (OTCH) is described in this paper. The presented method was based on the fact that OTCH could immensely enhance the CL of the reaction of cerium sulfate and tris(2,2‐bipyridyl) ruthenium (II) in acidic medium. Under optimal experimental conditions, CL intensity was favorably linear for OTCH in the range 5.0 × 10−7 to 5.0 × 10−5 g/ml, with a detection limit of 1.5 × 10−7 g/ml (S/N = 3). The relative standard detection was 4.76% for 5.0 × 10−6 g/ml (n = 11). This method was successfully applied to the analysis of OTCH in milk and egg white samples. According to the results of the kinetic curves for OTCH in the Ru(bipy)32+–Ce(SO4)2 CL system, together with CL and ultraviolet (UV)–visible spectra, the possible mechanism of the CL reaction is discussed briefly. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are considered to play essential roles in the process of origination, proliferation, migration, and invasion of cancer, and their properties are regulated by Wnt/β-catenin pathway. Phenethyl isothiocyanate (PEITC) is a natural product obtained from cruciferous vegetables with anticancer activities. The present study aimed to investigate the inhibitory effect and the underlying mechanisms of PEITC on colorectal CSCs. In this study, we found that PEITC can significantly reduce the size and number of colorectal cancer cell spheroids in serum-free medium. With increasing PEITC concentrations (10-40 μM), the number of spheroids was reduced to about 10% of the control group, and the percentage of CD133+ cells was decreased by about 3-16 folds. PEITC also decreased the expression of CSC markers. Meanwhile, inhibition of proliferation as well as induction of apoptosis of colorectal CSCs was observed after PEITC treatment. Furthermore, through activating Wnt/β-catenin pathway with LiCl, the inhibitory effects of PEITC on colorectal CSCs were diminished. Our data suggested that PEITC can be an effective inhibitor of colorectal CSCs by targeting Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Tissue-specific activation of DOF11 promotes rice resistance to sheath blight disease and increases grain weight via activation of SWEET14 (iii) One-thousand-grain weight of WT, sweet14, DOF11-VP16 and sweet14/DOF11-VP16 plants. (u) Western blot analysis was performed to detect DOF11-VP16-Myc levels using anti-Myc antibody in WT, dof11 and dof11/DOF11-VP16-Myc plants (#1, #2). Keywords: SWEET14; yield; sheath blight disease; DOF11; rice EN SWEET14 yield sheath blight disease DOF11 rice 409 411 3 03/15/21 20210301 NES 210301 Sugar will eventually be exported transporter (SWEET) is a family of sugar transporters that plays a critical role during host and pathogen interaction (Bezrutczyk I et al i ., 2018). [Extracted from the article]

Summary: What causes the disparity in biodiversity among regions is a fundamental question in biogeography, ecology, and evolutionary biology. Evolutionary and biogeographic processes (speciation, extinction, dispersal) directly determine species richness patterns, and can be studied using integrative phylogenetic approaches. However, the strikingly high richness of East Asia relative to other Northern Hemisphere regions remains poorly understood from this perspective. Here, for the first time, we test two general hypotheses (older colonization time, faster diversification rate) to explain this pattern, using the plant tribe Lysimachieae (Primulaceae) as a model system. We generated a new time‐calibrated phylogeny for Lysimachieae (13 genes, 126 species), to estimate colonization times and diversification rates for each region and to test the relative importance of these two factors for explaining regional richness patterns. We find that neither time nor diversification rates alone explain richness patterns among regions in Lysimachieae. Instead, a new index that combines both factors explains global richness patterns in the group and their high East Asian biodiversity. Based on our results from Lysimachieae, we suggest that the high richness of plants in East Asia may be explained by a combination of older colonization times and faster diversification rates in this region. [ABSTRACT FROM AUTHOR]

Knowledge on adaptive genetic variation in response to environmental variation is the key to understanding the adaptive evolution potential of species. China's warm-temperate zone is an important climatic zone, but only a few landscape genomics studies have been conducted to understand the adaptive evolution of regional vegetation. In this study, natural populations of Achyranthes bidentata Blume were sampled in China's warm-temperate zone to infer its adaptive evolution using landscape genomics methods. Four SCoT primers were used to investigate the adaptive evolution of A. bidentata in response to environmental variation across the warm-temperate zone of China. A total of 126 individuals from fifteen natural populations were successfully scored, and 202 unambiguous fragments were obtained. Twenty-three outlier loci were identified, eighteen outlier loci were significantly associated with environmental variables. Redundancy analytical results suggested that four environmental variables related to temperature and precipitation remarkably influenced the distribution of loci. The results provide empirical evidence that molecular markers with bias toward candidate functional genes might be suitable for landscape genomics studies. Temperature and precipitation jointly drive the adaptive evolution of A. bidentata. The key driving environmental factors identified in this study are mostly related to the ecological habit of A. bidentata. The species personality, i.e., ecological habit, seems to play an important role in the adaptive differentiation on A. bidentata. [ABSTRACT FROM AUTHOR]

The increasing intensity of exercise enhanced corticosterone and lactate production in both humans and rodents. Our previous studies also demonstrated that lactate could stimulate testosterone production in vivo and in vitro. However, the production of testosterone in response to combined corticosterone and lactate on Leydig cells, and underlying molecular mechanisms are remained unclear. This study investigated the changes in testosterone levels of Leydig cells upon exposure to lactate, corticosterone or combination of both, and revealed the detailed mechanisms. Leydig cells were isolated from rat testes, and treated with different concentrations of lactate (2.5-20 mM), cortiosterone (10−9-10−4 M) and lactate plus corticosterone. The production of testosterone were assayed by radioimmunoassay, and the key molecular proteins, including luteinizing hormone receptor (LHR), protein kinase A (PKA), steroidogenic acute regulatory protein (StAR), and cholesterol P450 side-chain cleavage enzyme (P450scc) involved in testosterone production were performed by Western blot. Results showed that testosterone levels were significantly increased with lactate, while decresed with corticosterone and lactate plus corticosterone treatment. Protein expressions of LHR and P450scc were upregulated with lactate treatment. However, PKA and P450scc were downregulated by lactate plus corticosterone treatment. This downregulation was followed by decreased testoterone levels in Leydig cells. Furthermore, acetylated cAMP, which activates testosterone production was increased with lactate, but not altered by conrtiosterone. Our findings conclude that corticosterone may interfere with lactate, and restrict lactate-stimulated testosterone production in Leydig cells. J. Cell. Physiol. 232: 2135-2144, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background & Aims The discovery of effective and reliable biomarkers to detect hepatitis B virus ( HBV)-positive hepatocellular carcinoma ( HCC) at an early stage may improve the survival of HCC. The aim of this study was to establish serum micro RNA (mi RNA) profiles as diagnostic biomarkers for HBV-positive HCC. Methods We used deep sequencing to screen serum mi RNAs in a discovery cohort (n=100). Quantitative polymerase chain reaction ( qPCR) assays were then applied to evaluate the expression of selected mi RNAs. A diagnostic 2-mi RNA panel was established by a logistic regression model using a training cohort (n=182). The predicted probability of being detected as HCC was used to construct the receiver operating characteristic ( ROC) curve. Area under the ROC curve ( AUC) was used to assess the diagnostic performance of the selected mi RNA panel. Results The predicted probability of being detected as HCC by the 2-mi RNA panel was calculated by: logit P=−2.988 + 1.299 × miR-27b-3p + 1.245 × miR-192-5p. These results were further confirmed in a validation cohort (n=246).The mi RNA panel provided a high diagnostic accuracy of HCC ( AUC=0.842, P<.0001 for training set; AUC=0.836, P<.0001 for validation set respectively). In addition, the mi RNA panel showed better prediction of HCC diagnosis than did alpha-foetoprotein ( AFP). The mi RNA panel also differentiated HCC from healthy ( AUC=0.823, P<.0001), and cirrhosis patients ( AUC=0.859, P<.0001) respectively. Conclusions Differentially expressed serum mi RNAs may have considerable clinical value in HCC diagnosis, and be particularly helpful for AFP-negative HCC. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/β-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We showed that the levels of lung CSC markers (CD133, CD44, ALDHA1, Nanog and Oct4) and the number of CD133-positive cells were significantly elevated in the sphere-forming cells. We further illustrated that curcumin efficiently abolished lung CSC traits, as evidenced by reduced tumorsphere formation, reduced number of CD133-positive cells, decreased expression levels of lung CSC markers, as well as proliferation inhibition and apoptosis induction. Moreover, we demonstrated that curcumin suppressed the activation of both Wnt/β-catenin and Sonic Hedgehog pathways. Taken together, our data suggested that curcumin exhibited its interventional effect on lung CSCs via inhibition of Wnt/β-catenin and Sonic Hedgehog pathways. These novel findings could provide new insights into the potential therapeutic application of curcumin in lung CSC elimination and cancer intervention. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Despite some notable successes, only a fraction of the genetic variation available in wild relatives has been utilized to produce superior wheat varieties. This is as a direct result of the lack of availability of suitable high-throughput technologies to detect wheat/wild relative introgressions when they occur. Here, we report on the use of a new SNP array to detect wheat/wild relative introgressions in backcross progenies derived from interspecific hexaploid wheat/ Ambylopyrum muticum F1 hybrids. The array enabled the detection and characterization of 218 genomewide wheat/ Am. muticum introgressions, that is a significant step change in the generation and detection of introgressions compared to previous work in the field. Furthermore, the frequency of introgressions detected was sufficiently high to enable the construction of seven linkage groups of the Am. muticum genome, thus enabling the syntenic relationship between the wild relative and hexaploid wheat to be determined. The importance of the genetic variation from Am. muticum introduced into wheat for the development of superior varieties is discussed. [ABSTRACT FROM AUTHOR]

The objective of the present study was to predict column design parameters using mathematical models such as bed depth service time (BDST) and the empty bed residence time (EBRT). The dynamic adsorption/desorption of anthocyanins from blueberry water extracts was conducted on Amberlite FPX-66 resin in a fixed bed column system. Blueberry anthocyanins were extracted with acidified hot water (90 °C) utilizing high power ultrasound. Breakthrough curves were obtained at different bed depths (5, 7.5, 10, 12.5 and 15 cm) and constant flow rate of 4.0 mL/min. Increase in bed height increased both the breakpoint and exhaustion point of the FPX-66 resin. The experimental data fitted well to BDST model at 5% of the breakthrough curve ( R2 = 0.9864). The EBRT was in the range of 3.75-10.25 min at different bed depths. In addition, desorption of anthocyanins was studied at different ethanol concentrations and sigmoid equation was applied to obtain maximum recovery rates. Practical Applications Anthocyanins are antioxidant flavonoids in blueberries. They are responsible for the blue color of the berries and are known to promote better health by preventing chronic diseases. A concentrated anthocyanin extract from blueberries has the potential to be used as dietary supplement, natural colorant and functional food ingredient. This present study optimized resin adsorption method to concentrate polyphenols and remove sugars using mathematical models. Optimization of the column design parameters can be used in designing a pilot/industrial scale column for the separation and concentration of anthocyanins from blueberries. [ABSTRACT FROM AUTHOR]