An organism-wide ATAC-seq peak catalog for the bovine and its use to identify regulatory variants.

We report the generation of an organism-wide catalog of 976,813 cis-acting regulatory elements for the bovine detected by the assay for transposase accessible chromatin using sequencing (ATAC-seq). We regroup these regulatory elements in 16 components by nonnegative matrix factorization. Correlation between the genome-wide density of peaks and transcription start sites, correlation between peak accessibility and expression of neighboring genes, and enrichment in transcription factor binding motifs support their regulatory potential. Using a previously established catalog of 12,736,643 variants, we show that the proportion of single-nucleotide polymorphisms mapping to ATAC-seq peaks is higher than expected and that this is owing to an approximately 1.3-fold higher mutation rate within peaks. Their site frequency spectrum indicates that variants in ATAC-seq peaks are subject to purifying selection. We generate eQTL data sets for liver and blood and show that variants that drive eQTL fall into liver- and blood-specific ATAC-seq peaks more often than expected by chance. We combine ATAC-seq and eQTL data to estimate that the proportion of regulatory variants mapping to ATAC-seq peaks is approximately one in three and that the proportion of variants mapping to ATAC-seq peaks that are regulatory is approximately one in 25. We discuss the implication of these findings on the utility of ATAC-seq information to improve the accuracy of genomic selection.

One-Dimensional Crystal-Structure Te-Se Alloy for Flexible Shortwave Infrared Photodetector and Imaging.

Flexible shortwave infrared detectors play a crucial role in wearable devices, bioimaging, automatic control, etc. Commercial shortwave infrared detectors face challenges in achieving flexibility due to the high fabrication temperature and rigid material properties. Herein, we develop a high-performance flexible Te0.7Se0.3 photodetector, resulting from the unique 1D crystal structure and small elastic modulus of Te-Se alloying. The flexible photodetector exhibits a broad-spectrum response ranging from 365 to 1650 nm, a fast response time of 6 µs, a broad linear dynamic range of 76 dB, and a specific detectivity of 4.8 × 1010 Jones at room temperature. The responsivity of the flexible detector remains at 93% of its initial value after bending with a small curvature of 3 mm. Based on the optimized flexible detector, we demonstrate its application in shortwave infrared imaging. These results showcase the great potential of Te0.7Se0.3 photodetectors for flexible electronics.

Effect of Different Cooking Methods on the Aroma and Taste of Chicken Broth.

A single combi oven, known for its versatility, is an excellent choice for a variety of chicken soup preparations. However, the impact of universal steam ovens on the flavor quality of chicken soup remains unclear. This study aimed to explore the impact of different cooking methods on the aroma and taste of chicken soup. Three cooking methods with various stewing times were compared: ceramic pot (CP), electric pressure cooker (EPC), and combi oven (CO). Analyses were conducted using electron-nose, electron-tongue, gas chromatography-ion mobility spectrometry (GC-IMS), automatic amino acid analysis, and chemometric methods. A total of 14 amino acids, including significant umami contributors, were identified. The taste components of CP and CO chicken soups were relatively similar. In total, 39 volatile aroma compounds, predominantly aldehydes, ketones, and alcohols, were identified. Aldehydes were the most abundant compounds, and 23 key aroma compounds were identified. Pearson's correlation analyses revealed distinct correlations between various amino acids (e.g., glutamic acid and serine) and specific volatile compounds. The aroma compounds from the CP and CO samples showed similarities. The results of this study provide a reference for the application of one-touch cooking of chicken soup in versatile steam ovens.

Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals.

BACKGROUND: Cohorts of individuals that have been genotyped and phenotyped for genomic selection programs offer the opportunity to better understand genetic variation associated with complex traits. Here, we performed an association study for traits related to body size and muscular development in intensively selected beef cattle. We leveraged multiple trait information to refine and interpret the significant associations. RESULTS: After a multiple-step genotype imputation to the sequence-level for 14,762 Belgian Blue beef (BBB) cows, we performed a genome-wide association study (GWAS) for 11 traits related to muscular development and body size. The 37 identified genome-wide significant quantitative trait loci (QTL) could be condensed in 11 unique QTL regions based on their position. Evidence for pleiotropic effects was found in most of these regions (e.g., correlated association signals, overlap between credible sets (CS) of candidate variants). Thus, we applied a multiple-trait approach to combine information from different traits to refine the CS. In several QTL regions, we identified strong candidate genes known to be related to growth and height in other species such as LCORL-NCAPG or CCND2. For some of these genes, relevant candidate variants were identified in the CS, including three new missense variants in EZH2, PAPPA2 and ADAM12, possibly two additional coding variants in LCORL, and candidate regulatory variants linked to CCND2 and ARMC12. Strikingly, four other QTL regions associated with dimension or muscular development traits were related to five (recessive) deleterious coding variants previously identified. CONCLUSIONS: Our study further supports that a set of common genes controls body size across mammalian species. In particular, we added new genes to the list of those associated with height in both humans and cattle. We also identified new strong candidate causal variants in some of these genes, strengthening the evidence of their causality. Several breed-specific recessive deleterious variants were identified in our QTL regions, probably as a result of the extreme selection for muscular development in BBB cattle.

Efficient Near-Infrared PbS Quantum Dot Solar Cells Employing Hydrogenated In2 O3 Transparent Electrode.

Infrared solar cells are regarded as candidates for expanding the solar spectrum of c-Si cells, and the window electrodes are usually transparent conductive oxide (TCO) such as widely used indium tin oxide material. However, due to the low transmittance of the TCO in the near-infrared region, most near-infrared light cannot penetrate the electrode and be absorbed by the active layer. Here, the propose a simple procedure to fabricate the window materials with high near-infrared transmittance and high electrical conductivity, namely the hydrogen-doped indium oxide (IHO) films prepared by room temperature magnetron sputtering. The low-temperature annealed IHO conductive electrodes exhibit high mobility of 98 cm2 V-1 s-1 and high infrared transmittance of 85.2% at 1300 nm, which endows the lead quantum dot infrared solar cell with an improved short-circuit current density of 37.2 mA cm-2 and external quantum efficiency of 70.22% at 1280 nm. The proposed preparation process is simple and compatible with existing production lines, which gifts the IHO transparent conductive film great potential in broad applications that simultaneously require high infrared transmittance and high conductivity.

Loss of function of a rice TPR-domain RNA-binding protein confers broad-spectrum disease resistance.

Crops carrying broad-spectrum resistance loci provide an effective strategy for controlling infectious disease because these loci typically confer resistance to diverse races of a pathogen or even multiple species of pathogens. Despite their importance, only a few crop broad-spectrum resistance loci have been reported. Here, we report the identification and characterization of the rice bsr-k1 (broad-spectrum resistance Kitaake-1) mutant, which confers broad-spectrum resistance against Magnaporthe oryzae and Xanthomonas oryzae pv oryzae with no major penalty on key agronomic traits. Map-based cloning reveals that Bsr-k1 encodes a tetratricopeptide repeats (TPRs)-containing protein, which binds to mRNAs of multiple OsPAL (OsPAL1-7) genes and promotes their turnover. Loss of function of the Bsr-k1 gene leads to accumulation of OsPAL1-7 mRNAs in the bsr-k1 mutant. Furthermore, overexpression of OsPAL1 in wild-type rice TP309 confers resistance to M. oryzae, supporting the role of OsPAL1 Our discovery of the bsr-k1 allele constitutes a significant conceptual advancement and provides a valuable tool for breeding broad-spectrum resistant rice.

[Effects and mechanisms of Supplemented Gegen Qinlian Decoction Formula against podocyte pyroptosis and insulin resistance in model rats with diabetic kidney disease].

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.

Junctional sarcoplasmic reticulum motility in adult mouse ventricular myocytes.

Excitation-contraction (EC) coupling is the coordinated process by which an action potential triggers cardiac myocyte contraction. EC coupling is initiated in dyads where the junctional sarcoplasmic reticulum (jSR) is in tight proximity to the sarcolemma of cardiac myocytes. Existing models of EC coupling critically depend on dyad stability to ensure the fidelity and strength of EC coupling, where even small variations in ryanodine receptor channel and voltage-gated calcium channel-α 1.2 subunit separation dramatically alter EC coupling. However, dyadic motility has never been studied. Here, we developed a novel strategy to track specific jSR units in dissociated adult ventricular myocytes using photoactivatable fluorescent proteins. We found that the jSR is not static. Instead, we observed dynamic formation and dissolution of multiple dyadic junctions regulated by the microtubule-associated molecular motors kinesin-1 and dynein. Our data support a model where reproducibility of EC coupling results from the activation of a temporally averaged number of SR Ca2+ release units forming and dissolving SR-sarcolemmal junctions. These findings challenge the long-held view that the jSR is an immobile structure and provide insights into the mechanisms underlying its motility.

[Anti-fibrotic mechanism of Sedum sarmentosum total flavanones in inhibiting activation of HSC by regulating Smads].

This paper was aimed to observe the interventional effect of Sedum sarmentosum total flavanones on hepatic fibrosis and its possible mechanism through the subcutaneous injection of CCl_4 in rats. Sixty male SD rats were randomly divided into normal control group, model group, low-dose, medium-dose, high-dose S. sarmentosum total flavanones groups(100, 200, 400 mg·kg~(-1)) and silymarin group(200 mg·kg~(-1)). The model of liver fibrosis was established by subcutaneous injection of rats with 40% CCl_4. After the modeling, the drug groups were intragastrically administered with corresponding drugs once a day for consecutively five weeks, while the normal group and the model group were given 0.9% sodium chloride solution during the same period. After the experiment, the general conditions of rats and the pathological changes of liver tissues were observed, and the contents of serum ALT, AST, HA and LN were measured. Besides, the expressions of the protein and relevant mRNA of Smad2/3, Smad4 and α-SMA in rats were detected. Compared with model group, S. sarmentosum total flavanones could significantly increase the rats' body weight, inhibit the increase of liver and spleen index in rats of liver fibrosis, reduce the levels of ALT, AST, HA and LN, and alleviate pathological changes. Meanwhile, compared with the model group, the protein expressions of Smad2/3, Smad4 and α-SMA as well as relevant mRNA expressions in S. sarmentosum total flavanones group were obviously decreased, while Smad7 expression was markedly increased. As a result, S. sarmentosum total flavanones could significantly alleviate CCl_4-induced liver fibrosis, and its anti-hepatic fibrosis mechanism may be related to intervention with Smads pathway, so as to inhibit the activation of HSC.

[Multi-targeted therapeutic effects of Huangkui Capsules on insulin resistance and urine microalbumin in early diabetic kidney disease patients].

To observe the multi-targeted therapeutic effects of Huangkui Capsules(HKC)on insulin resistance(IR)and urine microalbumin in the early diabetic kidney disease(DKD)patients. The case data from the 83 DKD patients at G2 and A2 stage were collected respectively and analyzed retrospectively. According to the different treatment,all patients were divided into the control(A)group(40 cases)and the treated(B)group(43 cases). Among them,the A group patients were received "routine basic treatment";the B group patients were received "routine basic treatment+HKC". For the 2 group patients,firstly,the baseline parameters before receiving the treatment were compared respectively,and then,the changes of the total scores of traditional Chinese medicine(TCM) syndromes and the indicators of IR,urine protein,renal function,blood lipids and safety after receiving the treatment for 8 weeks were compared,respectively. Furthermore,for the all patients,the correlation analysis between IR and urine protein or IR and the total scores of TCM syndromes was carried out,respectively. The results showed that,for the B group patients received "routine basic treatment",their total scores of TCM syndromes,urine protein indicators including urine microalbumin(micro-UAlb) and urine microalbumin/urinary creatinine(UACR),IR indicators including fasting serum insulin(FIN)and homeostasis model assessment of insulin resistance(HOMA-IR)were significantly improved,respectively. For the all DKD patients,before and after the treatment,the main IR indicators(FIN and HOMA-IR)were positively correlated with urine protein indicators(micro-UAlb and UACR). The main IR indicators(FIN and HOMA-IR) were also positively correlated with the total scores of TCM syndromes. In addition,2 treatments had no significant effects on renal function,blood lipids and safety indicators in the all DKD patients. Overall, "routine basic treatment+HKC" can ameliorate IR and reduce urine microalbumin in the early DKD patients. Its therapeutic targets may be not only proteinuria,but also IR,which is the upstream risk factor of proteinuria.

[Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways].

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 µg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated ß-galactosidase(SA-ß-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Loss of ß-adrenergic-stimulated phosphorylation of CaV1.2 channels on Ser1700 leads to heart failure.

L-type Ca2+ currents conducted by voltage-gated calcium channel 1.2 (CaV1.2) initiate excitation-contraction coupling in the heart, and altered expression of CaV1.2 causes heart failure in mice. Here we show unexpectedly that reducing ß-adrenergic regulation of CaV1.2 channels by mutation of a single PKA site, Ser1700, in the proximal C-terminal domain causes reduced contractile function, cardiac hypertrophy, and heart failure without changes in expression, localization, or function of the CaV1.2 protein in the mutant mice (SA mice). These deficits were aggravated with aging. Dual mutation of Ser1700 and a nearby casein-kinase II site (Thr1704) caused accelerated hypertrophy, heart failure, and death in mice with these mutations (STAA mice). Cardiac hypertrophy was increased by voluntary exercise and by persistent ß-adrenergic stimulation. PKA expression was increased, and PKA sites Ser2808 in ryanodine receptor type-2, Ser16 in phospholamban, and Ser23/24 in troponin-I were hyperphosphorylated in SA mice, whereas phosphorylation of substrates for calcium/calmodulin-dependent protein kinase II was unchanged. The Ca2+ pool in the sarcoplasmic reticulum was increased, the activity of calcineurin was elevated, and calcineurin inhibitors improved contractility and ameliorated cardiac hypertrophy. Cardio-specific expression of the SA mutation also caused reduced contractility and hypertrophy. These results suggest engagement of compensatory mechanisms, which initially may enhance the contractility of individual myocytes but eventually contribute to an increased sensitivity to cardiovascular stress and to heart failure in vivo. Our results demonstrate that normal regulation of CaV1.2 channels by phosphorylation of Ser1700 in cardiomyocytes is required for cardiovascular homeostasis and normal physiological regulation in vivo.

The Multivesicular Bodies (MVBs)-Localized AAA ATPase LRD6-6 Inhibits Immunity and Cell Death Likely through Regulating MVBs-Mediated Vesicular Trafficking in Rice.

Previous studies have shown that multivesicular bodies (MVBs)/endosomes-mediated vesicular trafficking may play key roles in plant immunity and cell death. However, the molecular regulation is poorly understood in rice. Here we report the identification and characterization of a MVBs-localized AAA ATPase LRD6-6 in rice. Disruption of LRD6-6 leads to enhanced immunity and cell death in rice. The ATPase activity and homo-dimerization of LRD6-6 is essential for its regulation on plant immunity and cell death. An ATPase inactive mutation (LRD6-6E315Q) leads to dominant-negative inhibition in plants. The LRD6-6 protein co-localizes with the MVBs marker protein RabF1/ARA6 and interacts with ESCRT-III components OsSNF7 and OsVPS2. Further analysis reveals that LRD6-6 is required for MVBs-mediated vesicular trafficking and inhibits the biosynthesis of antimicrobial compounds. Collectively, our study shows that the AAA ATPase LRD6-6 inhibits plant immunity and cell death most likely through modulating MVBs-mediated vesicular trafficking in rice.

[Triptolide inhibits NLRP3 inflammasome activation and ameliorates podocyte epithelial-mesenchymal transition induced by high glucose].

The aim of this paper was to explore the effects of triptolide( TP),the effective component of Tripterygium wilfordii on improving podocyte epithelial-mesenchymal transition( EMT) induced by high glucose( HG),based on the regulative mechanisms of Nod-like receptor protein 3( NLRP 3) inflammasome in the kidney of diabetic kidney disease( DKD). The immortalized podocytes of mice in vitro were divided into the normal( N) group,the HG( HG) group,the low dose of TP( L-TP) group,the high dose of TP( HTP) group and the mannitol( MNT) group,and treated by the different measures,respectively. More specifically,the podocytes in each group were separately treated by D-glucose( DG,5 mmol·L~(-1)) or HG( 30 mmol·L~(-1)) or HG( 30 mmol·L~(-1)) + TP( 5 µg·L~(-1))or HG( 30 mmol·L~(-1)) + TP( 10 µg·L~(-1)) or DG( 5 mmol·L~(-1)) + MNT( 24. 5 mmol·L~(-1)). After the treatment of HG or TP at 24,48 and 72 h,firstly,the activation of podocyte proliferation was investigated. Secondly,the protein expression levels of the epithelial markers in podocytes such as nephrin and ZO-1,the mesenchymal markers such as collagen Ⅰ and fibronectin( FN) were detected,respectively. Finally,the protein expression levels of NLRP3 and apoptosis-associated speck-like protein( ASC) as the key signaling molecules of NLRP3 inflammasome activation,as well as the downstream effector proteins including caspase-1,interleutin( IL)-1ß and IL-18 were examined,severally. The results indicated that,for the cultured podocytes in vitro,HG could cause the low protein expression levels of nephrin and ZO-1,induce the high protein expression levels of collagen Ⅰ and FN and trigger podocyte EMT. Also HG could cause the high protein expression levels of NLRP3,ASC,caspase-1,IL-1ß and IL-18 and induce NLRP3 inflammasome activation. On the other hand,the co-treatment of TP( L-TP or H-TP) and HG for podocytes could recover the protein expression levels of nephrin and ZO-1,inhibit the protein expression levels of collagen Ⅰ and FN and ameliorate podocyte EMT. Also the co-treatment of TP( L-TP or H-TP) and HG could down-regulate the protein expression levels of NLRP3 and ASC,inhibit NLRP3 inflammasome activation and reduce the protein expression levels of the downstream effector molecules including caspase-1,IL-1ß and IL-18. On the whole,HG could activate NLRP3 inflammasome and induce podocyte EMT in vitro. TP at the appropriate dose range could inhibit NLRP3 inflammasome activation and ameliorate podocyte EMT,which may be one of the critical molecular mechanisms of TP protecting againstpodocyte inflammatory injury in DKD.

Integrated Chemical and Transcriptomic Analysis Reveals the Distribution of Protopanaxadiol- and Protopanaxatriol-Type Saponins in Panax notoginseng.

Panax notoginseng is famous for its important therapeutic effects and commonly used worldwide. The active ingredients saponins have distinct contents in different tissues of P. notoginseng, and they may be related to the expression of key genes in the synthesis pathway. In our study, high-performance liquid chromatography results indicated that the contents of protopanaxadiol-(Rb1, Rc, Rb2, and Rd) and protopanaxatriol-type (R1, Rg1, and Re) saponins in below ground tissues were higher than those in above ground tissues. Clustering dendrogram and PCA analysis suggested that the below and above ground tissues were clustered into two separate groups. A total of 482 and 882 unigenes were shared in the below and above ground tissues, respectively. A total of 75 distinct expressions of CYPs transcripts (RPKM ≥ 10) were detected. Of these transcripts, 38 and 37 were highly expressed in the below ground and above ground tissues, respectively. RT-qPCR analysis showed that CYP716A47 gene was abundantly expressed in the above ground tissues, especially in the flower, whose expression was 31.5-fold higher than that in the root. CYP716A53v2 gene was predominantly expressed in the below ground tissues, especially in the rhizome, whose expression was 20.1-fold higher than that in the flower. Pearson's analysis revealed that the CYP716A47 expression was significantly correlated with the contents of ginsenoside Rc and Rb2. The CYP716A53v2 expression was associated with the saponin contents of protopanaxadiol-type (Rb1 and Rd) and protopanaxatriol-type (R1, Rg1, and Re). Results indicated that the expression patterns of CYP716A47 and CYP716A53v2 were correlated with the distribution of protopanaxadiol-type and protopanaxatriol-type saponins in P. notoginseng. This study identified the pivotal genes regulating saponin distribution and provided valuable information for further research on the mechanisms of saponin synthesis, transportation, and accumulation.

The complete chloroplast genome sequence and phylogenetic analysis of Chuanminshen (Chuanminshenviolaceum Sheh et Shan).

Chloroplast genome sequences are very useful for species identification and phylogenetics. Chuanminshen (Chuanminshen violaceum Sheh et Shan) is an important traditional Chinese medicinal plant, for which the phylogenetic position is still controversial. In this study, the complete chloroplast genome of Chuanminshen violaceum Sheh et Shan was determined. The total size of Chuanminshen chloroplast genome was 154,529 bp with 37.8% GC content. It has the typical quadripartite structure, a large single copy (17,800 bp) and a small single copy (84,171 bp) and a pair of inverted repeats (26,279 bp). The whole genome harbors 132 genes, which includes 85 protein coding genes, 37 tRNA genes, eight rRNA genes, and two pseudogenes. Thirty-nine SSR loci, 32 tandem repeats and 49 dispersed repeats were found. Phylogenetic analyses results with the help of MEGA showed a new insight for the Chuanminshen phylogenetic relationship with the reported chloroplast genomes in Apiales plants.

[EST-SSR identification, markers development of Ligusticum chuanxiong based on Ligusticum chuanxiong transcriptome sequences].

Ligusticum chuanxiong is a well-known traditional Chinese medicine plant. The study on its molecular markers development and germplasm resources is very important. In this study, we obtained 24 422 unigenes by assembling transcriptome sequencing reads of L. chuanxiong root. EST-SSR was detected and 4 073 SSR loci were identified. EST-SSR distribution and characteristic analysis results showed that the mono-nucleotide repeats were the main repeat types, accounting for 41.0%. In addition, the sequences containing SSR were functionally annotated in Gene Ontology (GO) and KEGG pathway and were assigned to 49 GO categories, 242 KEGG pathways, among them 2 201 sequences were annotated against Nr database. By validating 235 EST-SSRs,74 primer pairs were ultimately proved to have high quality amplification. Subsequently, genetic diversity analysis, UPGMA cluster analysis, PCoA analysis and population structure analysis of 34 L. chuanxiong germplasm resources were carried out with 74 primer pairs. In both UPGMA tree and PCoA results, L. chuanxiong resources were clustered into two groups, which are believed to be partial related to their geographical distribution. In this study, EST-SSRs in L. chuanxiong was firstly identified, and newly developed molecular markers would contribute significantly to further genetic diversity study, the purity detection, gene mapping, and molecular breeding.

Oxidative stress decreases microtubule growth and stability in ventricular myocytes.

Microtubules (MTs) have many roles in ventricular myocytes, including structural stability, morphological integrity, and protein trafficking. However, despite their functional importance, dynamic MTs had never been visualized in living adult myocytes. Using adeno-associated viral vectors expressing the MT-associated protein plus end binding protein 3 (EB3) tagged with EGFP, we were able to perform live imaging and thus capture and quantify MT dynamics in ventricular myocytes in real time under physiological conditions. Super-resolution nanoscopy revealed that EB1 associated in puncta along the length of MTs in ventricular myocytes. The vast (~80%) majority of MTs grew perpendicular to T-tubules at a rate of 0.06µm∗s(-1) and growth was preferentially (82%) confined to a single sarcomere. Microtubule catastrophe rate was lower near the Z-line than M-line. Hydrogen peroxide increased the rate of catastrophe of MTs ~7-fold, suggesting that oxidative stress destabilizes these structures in ventricular myocytes. We also quantified MT dynamics after myocardial infarction (MI), a pathological condition associated with increased production of reactive oxygen species (ROS). Our data indicate that the catastrophe rate of MTs increases following MI. This contributed to decreased transient outward K(+) currents by decreasing the surface expression of Kv4.2 and Kv4.3 channels after MI. On the basis of these data, we conclude that, under physiological conditions, MT growth is directionally biased and that increased ROS production during MI disrupts MT dynamics, decreasing K(+) channel trafficking.

Four receptor-like cytoplasmic kinases regulate development and immunity in rice.

Receptor-like cytoplasmic kinases (RLCKs) represent a large family of proteins in plants. However, few RLCKs have been well characterized. Here, we report the functional characterization of four rice RLCKs - OsRLCK57, OsRLCK107, OsRLCK118 and OsRLCK176 from subfamily VII. These OsRLCKs interact with the rice brassinosteroid receptor, OsBRI1 in yeast cell, but not the XA21 immune receptor. Transgenic lines silenced for each of these genes have enlarged leaf angles and are hypersensitive to brassinolide treatment compared to wild type rice. Transgenic plants silenced for OsRLCK57 had significantly fewer tillers and reduced panicle secondary branching, and lines silenced for OsRLCK107 and OsRLCK118 produce fewer seeds. Silencing of these genes decreased Xa21 gene expression and compromised XA21-mediated immunity to Xanthomonas oryzae pv. oryzae. Our study demonstrates that these OsRLCKs negatively regulate BR signalling, while positively regulating immune responses by contributing to the expression of the immune receptor XA21.

Balancing Industry and Drug Policy Objectives in the Pharmaceutical Sector: The Case of China.

Objectives This article assessed the balance between industry and drug policy objectives in the pharmaceutical sector in China. Methods The articles were mainly identified through databases such as Elsevier, Google Scholar, and SpringerLink, among others. Related articles were mainly separated into three categories: studies on drug policies, studies related to China's new health-care reform policy, and studies concerning patent policies. Results A relatively healthy environment for continuous innovation and drug patent protection in the pharmaceutical industry has been created in China, and the public's drug benefits have also significantly improved. However, the balance between industrial and drug policy objectives in the pharmaceutical sector in China requires additional attention. Discussion and conclusions The results suggest that the government should pay more attention to incentivizing enterprises' innovation, but the current Essential Medicines System in China has limited innovation. Hence, the mechanism for selecting essential medicines should be reformed, and certain appropriate and reasonably innovative medicines should be included. Additionally, medicine coverage, especially the coverage of essential drugs for primary care should be expanded to improve public health benefits. Furthermore, the pharmaceutical industry should be incorporated into the prospective National Drug Policy to achieve a balance between public benefits and pharmaceutical industry development in the future.