Effects of TrPLDs on the pathogenicity of Trichothecium roseum infected apple fruit.

Phospholipase D plays a critical regulatory role in the pathogenicity of filamentous fungi. However, the molecular mechanism of PLD regulating the pathogenicity of filamentous fungi has not been reported. In this research, the previously constructed TrPLD1 and TrPLD2 (TrPLDs) mutants were used as test strains. Firstly, the function of TrPLDs in Trichothecium roseum was studied. Then, the effects of TrPLDs on the pathogenicity of T. roseum and the quality of the inoculated apples were verified. The results suggested that the deletion of TrPLD1 delayed the spore germination of ΔTrPLD1 and inhibited germ tube elongation by down-regulating the expressions of TrbrlA, TrabaA and TrwetA. By down-regulating the extracellular enzyme-coding gene expressions, ΔTrPLD1 inhibited the degradation of apple fruit cell wall and the change of fatty acid content during infection, reduced the cell membrane permeability and malondialdehyde (MDA) content of apple fruit, thereby maintaining the integrity of fruit cell membrane, and reduced the pathogenicity of ΔTrPLD1 to apple and kept the quality of apple. However, ΔTrPLD2 did not have a significant effect on the infection process of apple fruit by the pathogen.

Regulation of carbohydrate metabolism during anther development in a thermo-sensitive genic male-sterile wheat line.

Bainong sterility (BNS) is a thermo-sensitive genic male sterile wheat line, characterised by anther fertility transformation in response to low temperature (LT) stress during meiosis, the failure of vacuole decomposition and the absence of starch accumulation in sterile bicellular pollen. Our study demonstrates that the late microspore (LM) stage marks the transition from the anther growth to anther maturation phase, characterised by the changes in anther structure, carbohydrate metabolism and the main transport pathway of sucrose (Suc). Fructan is a main storage polysaccharide in wheat anther, and its synthesis and remobilisation are crucial for anther development. Moreover, the process of pollen amylogenesis and the fate of the large vacuole in pollen are closely intertwined with fructan synthesis and remobilisation. LT disrupts the normal physiological metabolism of BNS anthers during meiosis, particularly affecting carbohydrate metabolism, thus determining the fate of male gametophytes and pollen abortion. Disruption of fructan synthesis and remobilisation regulation serves as a decisive event that results in anther abortion. Sterile pollen exhibits common traits of pollen starvation and impaired starch accumulation due to the inhibition of apoplastic transport starting from the LM stage, which is regulated by cell wall invertase TaIVR1 and Suc transporter TaSUT1.

Ozone Application Suppressed the Blue Mold Development and Maintained the Main Active Ingredients Content of Postharvest Fresh Codonopsis pilosula during Storage.

Penicillium expansum is the predominant causal agent causing blue mold in postharvest fresh Codonopsis pilosula during storage. The pathogen reduces the yield and affects the quality of C. pilosula and even generates patulin, threatening human health. In this study, postharvest fresh, healthy C. pilosula was sprayed with P. expansum, and the control effect of ozone on postharvest diseases of C. pilosula was studied, and the effect of ozone on the contents in the main active ingredients of C. pilosula was compared; finally, the effect of ozone on reactive oxygen species (ROS) metabolism in C. pilosula was analyzed. The results showed that 2 mg L-1 ozone application significantly inhibited the occurrence of postharvest blue mold caused by P. expansum, reduced weight loss rate, controlled the accumulation of patulin and maintained the contents of the main active components in C. pilosula. The study will provide a theoretical basis for ozone treatment to control the occurrence of postharvest diseases of C. pilosula.

ROS mediated by TrPLD3 of Trichothecium roseum participated cell membrane integrity of apple fruit by influencing phosphatidic acid metabolism.

Trichothecium roseum is a typical necrotrophic fungal pathogen that not only bring about postharvest disease, but contribute to trichothecenes contamination in fruit and vegetables. Phospholipase D (PLD), as an important membrane lipid degrading enzyme, can produce phosphatidic acid (PA) by hydrolyzing phosphatidylcholine (PC) and phosphatidylinositol (PI). PA can promote the production of reactive oxygen species (ROS) by activating the activity of NADPH oxidase (NOX), thereby increasing the pathogenicity to fruit. However, the ROS mediated by TrPLD3 how to influence T. roseum infection to fruit by modulating phosphatidic acid metabolism, which has not been reported. In this study, the knockout mutant and complement strain of TrPLD3 were constructed through homologous recombination, TrPLD3 was tested for its effect on the colony growth and pathogenicity of T. roseum. The experimental results showed that the knockout of TrPLD3 inhibited the colony growth of T. roseum, altered the mycelial morphology, completely inhibited the sporulation, and reduced the accumulation of T-2 toxin. Moreover, the knockout of TrPLD3 significantly decreased pathogenicity of T. roseum on apple fruit. Compared to inoculated apple fruit with the wide type (WT), the production of ROS in apple infected with ΔTrPLD3 was slowed down, the relative expression and enzymatic activity of NOX, and PA content decreased, and the enzymatic activity and gene expression of superoxide dismutase (SOD) increased. In addition, PLD, lipoxygenase (LOX) and lipase activities were considerably decreased in apple fruit infected with ΔTrPLD3, the changes of membrane lipid components were slowed down, the decrease of unsaturated fatty acid content was alleviated, and the accumulation of saturated fatty acid content was reduced, thereby maintaining the cell membrane integrity of the inoculated apple fruit. We speculated that the decreased PA accumulation in ΔTrPLD3-inoculated apple fruit further weakened the interaction between PA and NOX on fruit, resulting in the reduction of ROS accumulation of fruits, which decreased the damage to the cell membrane and maintained the cell membrane integrity, thus reducing the pathogenicity to apple. Therefore, TrPLD3-mediated ROS plays a critical regulatory role in reducing the pathogenicity of T. roseum on apple fruit by influencing phosphatidic acid metabolism.

Targeting the JAK2/STAT3 signaling pathway with natural plants and phytochemical ingredients: A novel therapeutic method for combatting cardiovascular diseases.

The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials.

Investigating the mechanism of phosphorene nanoribbon synthesis by discharging black phosphorus intercalation compounds.

Phosphorene nanoribbons (PNRs) can be synthesised in intrinsically scalable methods from intercalation of black phosphorus (BP), however, the mechanism of ribbonisation remains unclear. Herein, to investigate the point at which nanoribbons form, we decouple the two key synthesis steps: first, the formation of the BP intercalation compound, and second, the dissolution into a polar aprotic solvent. We find that both the lithium intercalant and the negative charge on the phosphorus host framework can be effectively removed by addition of phenyl cyanide to return BP and investigate whether fracturing to ribbons occurred after the first step. Further efforts to exfoliate mechanically with or without solvent reveal that the intercalation step does not form ribbons, indicating that an interaction between the amidic solvent and the intercalated phosphorus compound plays an important role in the formation of nanoribbons.

The small GTPase Ypt7 of Penicillium expansum is required for growth, patulin biosynthesis and virulence.

Ypt GTPases are the largest subfamily of small GTPases involved in membrane transport. Here, a PeYpt7 gene deletion mutant of P. expansum was constructed. The ΔPeYpt7 mutant showed reduced colony growth with abnormal mycelial growth, reduced conidiation, and insufficient spore development. The mutation rendered the pathogen susceptible to osmotic stress and cell wall stressors. In addition, the absence of PeYpt7 reduced patulin production in P. expansum and significantly limited gene expression (PatG, PatH, PatI, PatD, PatF, and PatL). In addition, the mutant showed attenuated virulence in infected fruit and reduced expression of pathogenic factors was (PMG, PG, PL, and GH1). Thus, PeYpt7 modulates the growth, morphology, patulin accumulation, and pathogenicity of P. expansum by limiting the expression of related genes.

A clock-dependent brake for rhythmic arousal in the dorsomedial hypothalamus.

Circadian clocks generate rhythms of arousal, but the underlying molecular and cellular mechanisms remain unclear. In Drosophila, the clock output molecule WIDE AWAKE (WAKE) labels rhythmic neural networks and cyclically regulates sleep and arousal. Here, we show, in a male mouse model, that mWAKE/ANKFN1 labels a subpopulation of dorsomedial hypothalamus (DMH) neurons involved in rhythmic arousal and acts in the DMH to reduce arousal at night. In vivo Ca2+ imaging reveals elevated DMHmWAKE activity during wakefulness and rapid eye movement (REM) sleep, while patch-clamp recordings show that DMHmWAKE neurons fire more frequently at night. Chemogenetic manipulations demonstrate that DMHmWAKE neurons are necessary and sufficient for arousal. Single-cell profiling coupled with optogenetic activation experiments suggest that GABAergic DMHmWAKE neurons promote arousal. Surprisingly, our data suggest that mWAKE acts as a clock-dependent brake on arousal during the night, when mice are normally active. mWAKE levels peak at night under clock control, and loss of mWAKE leads to hyperarousal and greater DMHmWAKE neuronal excitability specifically at night. These results suggest that the clock does not solely promote arousal during an animal's active period, but instead uses opposing processes to produce appropriate levels of arousal in a time-dependent manner.

Pathogenicity, Mycotoxin Production, and Control of Potato Dry Rot Caused by Fusarium spp.: A Review.

Fusarium dry rot is one of the major potato diseases during storage after harvest, which not only results in quality degradation but also causes great economic losses. The disease can be elicited by some species of Fusarium, and the pathogenic fungi of Fusarium causing potato dry rot are considerably diverse in various countries and regions. The disease caused by Fusarium spp. is associated with mycotoxins accumulation, which has phytotoxic and mycotoxic effects on humans and animals. Chemical synthetic fungicide is considered the main control measure for the Fusarium dry rot of potato; nevertheless, it is unfortunate that persistent application inevitably results in the emergency of a resistant strain and environmental contamination. A comprehensive disease control strategy includes potato cultivar selection, appropriate cultural practices (crop rotation, cultivate pattern, fertilization, and irrigation), harvesting processes and postharvest treatments (harvesting, classification, packaging, wound healing), and storage conditions (environmental disinfection, temperature, humidity and gas composition) along with the application of fungicide pre-harvest or post-harvest. Recently, emerging studies have indicated that eco-friendly strategies include physical control, chemical methods (such as the application of generally-recognised-as-safe (GRAS) compounds or chemical (elicitors) and biological control have been introduced to combat the Fusarium dry rot of potato.

Post-synthetic modification of a magnetic covalent organic framework with alkyne linkages for efficient magnetic solid-phase extraction and determination of trace basic orange II in food samples.

Efficient magnetic solid phase extraction using covalent organic frameworks (COFs) can find important applications in food safety. In this work, a sulfonate-functionalized magnetic COF (Fe3O4@COF-SO3Na) was synthesized by self-polycondensation of two-in-one monomer 1,6-bis(4-formylphenyl)-3,8-bis((4-aminophenyl) ethynyl)) pyrene (BFBAEPy) on the surface of aminated Fe3O4 and a thiol-yne click reaction. It was further adopted as an adsorbent for the efficient magnetic solid-phase extraction (MSPE) of basic orange II. The selective adsorption experiment indicated that it displayed selective adsorption ability to basic orange II due to the ion exchange, hydrogen bonds, and π-π interactions. Under the optimized conditions, the proposed MSPE method coupled with HPLC-DAD showed excellent linearity in the range of 0.05-0.5 µg/mL (R2 = 0.9997) for basic orange II. The lower limits of detection (LODs) for basic orange II were 1.0-1.4 µg/L for three food samples: yellow croaker, paprika and dried bean curd. The recoveries were 90.1-98.8% with relative standard deviations (RSDs) below 4.2%. Therefore, this work provides an effective strategy to modify magnetic COFs as absorbents in MSPE. Due to the tunability of functional groups in thiol­yne click reactions, the functional groups of magnetic COFs can be readily designed to enrich their multifunctional applications. Meanwhile, this work proposed a new method to detect trace amounts of basic orange II in food samples.

Effects of alpha-lipoic acid on sperm quality in patients with varicocele-related male infertility: study protocol for a randomized controlled clinical trial.

BACKGROUND: Varicocele is a high incidence and is considered to be the most common and correctable cause of male infertility. Oxidative stress (OS) plays a central role in the pathogenesis of varicocele-related male infertility. In addition to varicocelectomy, antioxidant supplementation seems to be an effective scheme for the treatment of varicocele-related male infertility, but it is still controversial. The purpose of this study is to determine the effects of alpha-lipoic acid (ALA) supplementation on sperm quality in patients with varicocele-related male infertility. METHODS: In this randomized controlled clinical trial, we will randomize 80 patients with varicocele-related male infertility from Guilin People's Hospital. The non-surgical observation group (n = 20) will receive ALA, the non-surgical control group (n = 20) will receive vitamin E, the surgical observation group (n = 20) will receive ALA after the operation, and the surgical control group (n = 20) will receive vitamin E after the operation. The course of treatment will be 3 months. The results will compare the changes in semen parameters, sex hormones, testicular volume, sperm DNA fragment index (DFI), seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) between the groups at baseline and after 3 months of antioxidant supplementation. DISCUSSION: Whether it is necessary to use antioxidants in varicocele-related male infertility, how potent antioxidants should be used, postoperative application or non-surgical independent application still needs to be explored. This study attempts to compare the effects of two antioxidants (ALA and vitamin E) on sperm quality in patients with varicocele-related male infertility (surgical or non-surgical) and attempted to answer the above questions. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100054958. Registered on 29 December 2021.

Potential molecular mechanism of the Xiexin capsule in the intervention of dyslipidemia based on bioinformatics and molecular docking.

Introduction: Objective: bioinformatic methods and molecular docking technology were used to predict the active components, targets, and related biological pathways of the Xiexin capsule in the intervention for dyslipidemia, exploring its mechanism. Methods: the active components and targets of the Xiexin capsule were screened by the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform )database. Genecards (The Human Gene Database), OMIM (Online Mendelian Inheritance in Man), PharmGkb (Pharmacogenomics Knowledge Base database), TTD (Therapeutic Target Database), and Drugbank platforms were used to search the disease targets of dyslipidemia. The Cytoscape 3.8.0 software was used to construct the 'component-target' network diagram, and the STRING (functional protein association networks) platform was used to analyze protein-protein interaction (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed by R language data packets to predict the mechanism of action. The AutoDockVina and PyMol software were used to dock the key active components in the Xiexin capsule and the core proteins in PPI. Results: a total of 66 effective components were screened, involving 114 targets; 87 key active compounds were screened from the 'drug-component-target' diagram. The PPI network mainly involved core proteins such as PTGS2 (prostaglandin-endoperoxide synthase 2), PTGS1 (prostaglandin-endoperoxide synthase 1), and HSP90AA1 (heat shock protein 90 alpha family class A member 1). GO and KEGG enrichment analysis results of common targets mainly involved hormone-mediated signaling pathway, steroid hormone response, lipid transport and metabolism, regulation of cholesterol storage, cyclooxygenase pathway, and other biological pathways, as well asMM PPAR (peroxisome proliferators-activated receptor) signaling pathway, IL-17 (interleukin 17) signaling pathway, PI3K-Akt (protein kinase b) signaling pathway, FcεRI signaling pathway, and other related pathways. Molecular docking verification showed that quercetin had the best binding with the core target protein HSP90AA1, and HSP90AA1 was the target protein with the best binding activity for the key chemical components in Xiexin capsules. Conclusion: the main chemical components in the Xiexin capsules may participate in the regulation of PPAR and other signaling pathways by regulating key genes such as ESR1 (estrogen receptor 1), MAPK14 (mitogen-activated protein kinase 14), and HSP90AA1, to exert the pharmacological effect of the intervention on dyslipidemia.

Introducción: Objetivo: se utilizaron métodos bioinformáticos y técnicas de acoplamiento molecular para predecir componentes efectivos, objetivos y vías biológicas relacionadas de la cápsula Xiexin en la intervención de dislipidemia y explorar su mecanismo. Métodos: los componentes activos y los objetivos de la cápsula Xiexin fueron seleccionados por la base de datos TCMSP. Se utilizaron plataformas Genecards, OMIM, PharmGkb, Therapeutic Target Database y Drugbank para buscar dianas de la enfermedad en la dislipidemia. El diagrama reticular "componente-diana" fue construido por el software Cytoscape 3.7.0, y la interacción proteína-proteína (PPI) fue analizada por la plataforma STRING. Los análisis de enriquecimiento de Gene Ontology (GO) y Kyoto Encyclopedia of Genes and Genomics se realizaron mediante paquetes de datos en lenguaje R para predecir mecanismo de acción. El software AutoDockVina y PyMol se utilizó para unir componentes activos clave de la cápsula Xiexin y las proteínas clave de la PPI. Resultados: se seleccionaron 65 componentes activos y 114 dianas. Veintitrés compuestos activos clave fueron seleccionados a partir de la tabla "componentes farmacéuticos-dianas". Las redes PPI incluyen principalmente proteínas básicas como PTGS2, PTGS1 y HSP90AA1. Los resultados del análisis de enriquecimiento de GO y KEGG en los objetivos comunes se refieren principalmente a la vía de señalización mediada por esteroides, la respuesta hormonal esteroidea, el transporte y metabolismo lipídicos, la regulación del almacenamiento de colesterol, la vía de la ciclooxigenasa y otras vías biológicas, así como la vía de señalización de PPAR, IL-17, PI3K-Akt, FcεRI y otras vías relacionadas. La prueba de acoplamiento molecular mostró que la quercetina se une mejor a la proteína diana central HSP90AA1, que es la proteína diana con la mejor actividad de unión de los componentes químicos clave de la cápsula Xiexin. Conclusión: los principales componentes químicos de la cápsula Xiexin pueden participar en la regulación de la PPAR y otras vías de señalización mediante la regulación de genes clave como ESR1, MAPK14 (mitogen-activated protein kinase 14), HSP90AA1, por lo que pueden desempeñar un papel farmacológico en la intervención de dislipidemia.

Complete genome sequence of peony leafroll-associated virus, a novel ampelovirus in subgroup I.

The complete genome sequence of peony leafroll-associated virus (PLRaV) was determined by deep sequencing of ribosomal-RNA-depleted total RNA extracted from a peony plant exhibiting leafroll symptoms. Further PCR and RACE analysis showed that the PLRaV genome consists of 15,406 nucleotides and contains 10 putative open reading frames, with an organization typical of members of the genus Ampelovirus, family Closteroviridae. Amino acid sequence comparisons showed that the viral heat shock protein 70 homolog (HSP70h) shared the highest sequence identity (41.7%) with the corresponding region of grapevine leafroll-associated virus 1, and the coat protein (CP) and RNA-dependent RNA polymerase (RdRp) shared the highest sequence identity (32.1% and 52.3%, respectively) with grapevine leafroll-associated virus 13. Phylogenetic analysis of the HSP70h, CP, and RdRp aa sequences showed that PLRaV clustered with members of subgroup I of the genus Ampelovirus.

A rapid, simple, and highly efficient method for VIGS and in vitro-inoculation of plant virus by INABS applied to crops that develop axillary buds and can survive from cuttings.

BACKGROUND: Virus-induced gene silencing (VIGS) is one of the most convenient and powerful methods of reverse genetics. In vitro-inoculation of plant virus is an important method for studying the interactions between viruses and plants. Agrobacterium-based infiltration has been widely adopted as a tool for VIGS and in vitro-inoculation of plant virus. Most agrobacterium-based infiltration methods applied to VIGS and virus inoculation have the characteristics of low transformation efficiencies, long plant growth time, large amounts of plant tissue, large test spaces, and complex preparation procedures. Therefore, a rapid, simple, economical, and highly efficient VIGS and virus inoculation method is in need. Previous studies have shown that the selection of suitable plant tissues and inoculation sites is the key to successful infection. RESULTS: In this study, Tobacco rattle virus (TRV) mediated VIGS and Tomato yellow leaf curl virus (TYLCV) for virus inoculation were developed in tomato plants based on the agrobacterium tumefaciens-based infiltration by injection of the no-apical-bud stem section (INABS). The no-apical-bud stem section had a "Y- type" asymmetric structure and contained an axillary bud that was about 1-3 cm in length. This protocol provides high transformation (56.7%) and inoculation efficiency (68.3%), which generates VIGS transformants or diseased plants in a very short period (8 dpi). Moreover, it greatly reduces the required experimental space. This method will facilitate functional genomic studies and large-scale disease resistance screening. CONCLUSIONS: Overall, a rapid, simple, and highly efficient method for VIGS and virus inoculation by INABS was developed in tomato. It was reasonable to believe that it can be used as a reference for the other virus inoculation methods and for the application of VIGS to other crops (such as sweet potato, potato, cassava and tobacco) that develop axillary buds and can survive from cuttings.

Facile preparation of core-shell magnetic organic covalent framework via self-polymerization of two-in-one strategy as a magnetic solid-phase extraction adsorbent for determination of Rhodamine B in food samples.

The monomer of two-in-one molecular design strategy (i.e., A2B2 type monomer) 1,6-bis(4-formylphenyl)-3,8-bis((4-aminophenyl) ethynyl)) pyrene (BFBAEPy) was self-polymerized and coated on the modified Fe3O4 surface to synthesize a magnetic covalent organic framework (Fe3O4@COF) nanocomposite with a core-shell structure. Before high-performance liquid chromatography with ultraviolet detection (HPLC-UV) determination, Fe3O4@COF was used as a magnetic solid-phase extraction (MSPE) adsorbent to enrich Rhodamine B (RhB) illegally added to Chili powder and Chinese prickly ash. It had a large specific surface area and suitable pore size, which promoted the efficient adsorption of RhB dye and eliminated the interference of the matrix. Several key parameters affecting the extraction recovery rate were investigated, including adsorption capacity, adsorption time, pH, ionic strength, elution solvent, elution volume and elution time. Under the best optimized conditions, within the linear detection range of 0.05-5 µg/mL for RhB with the limit of detection (LOD) was 0.0038 µg/mL, excellent linearity (correlation coefficient R2=0.9997), and good repeatability (relative standard deviations RSD%< 3.8%), satisfactory extraction recovery rate (91.7%-97.5%). Therefore, the application of the established method to the detection of RhB in food samples has bright prospects.

Effect of Ambient pH on Growth, Pathogenicity, and Patulin Production of Penicillium expansum.

Penicillium expansum is an important postharvest pathogen of pomaceous fruit and a causal agent of blue mold or soft rot. In this study, we investigated the effect of ambient pH on growth, ultrastructure alteration, and pathogenicity of P. expansum, as well as accumulation of patulin and expression of genes involved in patulin biosynthesis. Under different pH, the fungus was routinely cultured and collected for growth, pathogenicity, patulin production, and gene expression studies using transmission electron microscopy, apple inoculation, HPLC, and RT-qPCR methods. Different ambient pH had significant impact on expression of genes and growth factors involved in patulin biosynthesis. Under same range of pH, gene expression profile, growth factors, and patulin accumulation (in vivo and in vitro) all showed similar changing trends. A well-developed cell was observed in addition to upregulation of genes at pH between pH 5.0 and 7.0, while the opposite was observed when pH was too basic (8.5) or too acid (2.5). Additionally, ambient pH had direct or indirect influence on expression of PecreaA, PelaeA, and PepacC. These findings will help in understanding the effect of ambient pH on growth, pathogenicity, and patulin production and support the development of successful methods for combating P. expansum infection on apple fruits.

Association Between Diabetes Medications and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: Diabetes mellitus (DM) increases the risk of Parkinson's disease (PD). However, whether DM medications play a part on that increased PD risk is unclear. We designed this meta-analysis to assess the influence of different oral DM medications on the PD risk in patients with DM. Methods: We searched PubMed, Embase, and CENTRAL databases for relevant studies up until January 2021. We pooled adjusted outcomes to assess the PD risk in patients using different DM medications including sulfonylurea, metformin, glitazones (GTZ), dipeptidyl peptidase-4 inhibitors (DPP4i), and glucagon-like peptide-1 agonists (GLP1a). Results: We included 10 studies in our analysis. Our results indicate a lack of significant association between the PD risk and the use of sulfonylureas (three studies; HR, 1.26; 95% CI, 0.95 to 1.66; I 2, 70%; p = 0.11), DPP4i (three studies; HR, 0.69; 95% CI, 0.35 to 1.38; I 2, 88%; p = 0.30), metformin (five studies; HR, 1.23; 95% CI, 0.98 to 1.78; I 2, 84%; p = 0.13), and GTZ (six studies; HR, 0.88; 95% CI, 0.66 to 1.16; I 2, 92%; p = 0.35). After exclusion of a single study in the GTZ analysis, our results indicate a significantly reduced PD risk with GTZ use (HR, 0.78; 95% CI, 0.65 to 0.93; I 2, 59%; p = 0.06). Similarly, after the exclusion of a single study, our results indicate a significantly increased PD risk with the use of metformin (HR, 1.50; 95% CI, 1.11 to 2.02; I 2, 80%; p = 0.008). We also found a significantly reduced PD risk with the use of GLP1a (two studies; HR, 0.41; 95% CI, 0.19 to 0.87; I 2, 0%; p = 0.02). Conclusion: The role of different DM medications on the PD risk remains unclear, and the quality of studies is low. While our analysis suggests a lack of association between the use of metformin, GTZ, DPP4i, and sulfonylureas and the PD risk, metformin (to a higher degree) and GTZ may still increase the risk. Limited data suggest a protective effect of GLP1a on the PD risk.

Lenghu on the Tibetan Plateau as an astronomical observing site.

On Earth's surface, there are only a handful of high-quality astronomical sites that meet the requirements for very large next-generation facilities. In the context of scientific opportunities in time-domain astronomy, a good site on the Tibetan Plateau will bridge the longitudinal gap between the known best sites1,2 (all in the Western Hemisphere). The Tibetan Plateau is the highest plateau on Earth, with an average elevation of over 4,000 metres, and thus potentially provides very good opportunities for astronomy and particle astrophysics3-5. Here we report the results of three years of monitoring of testing an area at a local summit on Saishiteng Mountain near Lenghu Town in Qinghai Province. The altitudes of the potential locations are between 4,200 and 4,500 metres. An area of over 100,000 square kilometres surrounding Lenghu Town has a lower altitude of below 3,000 metres, with an extremely arid climate and unusually clear local sky (day and night)6. Of the nights at the site, 70 per cent have clear, photometric conditions, with a median seeing of 0.75 arcseconds. The median night temperature variation is only 2.4 degrees Celsius, indicating very stable local surface air. The precipitable water vapour is lower than 2 millimetres for 55 per cent of the night.

A Ricin B-Like Lectin Protein Physically Interacts with TaPFT and Is Involved in Resistance to Fusarium Head Blight in Wheat.

Fusarium head blight (FHB), mainly caused by Fusarium graminearum, has become one of the most serious diseases that damage wheat. The TaPFT (pore-forming toxin-like) and TaHRC (histidine-rich calcium-binding protein) genes at the quantitative trait locus Fhb1 were identified to confer resistance to FHB in the wheat cultivar Sumai 3. In this study, a wheat ricin B-like lectin gene (designated TaRBL) that interacted with TaPFT was isolated by a yeast two-hybrid screen of a wheat cDNA library. A yeast two-hybrid and bimolecular fluorescence complementation study further verified that TaRBL interacted with TaPFT but not with TaHRC. Gene expression studies showed that upon F. graminearum infection, TaRBL expression was upregulated in resistant cultivars but downregulated in susceptible cultivars. Furthermore, knockdown of TaRBL expression by barley stripe mosaic virus-induced gene silencing significantly reduced the resistance of wheat to FHB in both the resistant cultivar Sumai 3 and the susceptible cultivar Jimai 22. Thus, we conclude that TaRBL encodes a ricin B-like lectin protein that interacts with TaPFT and is involved in resistance to FHB in wheat.

Bioinformatics Analysis and Identification of Genes and Molecular Pathways Involved in Venous Thromboembolism (VTE).

OBJECTIVES: To explore the key genes, and correlated pathways in venous thromboembolism (VTE) via bioinformatic analysis, and expected our findings could contribute to the development of new biomarkers and therapeutic target for VTE. METHODS: Two VTE-related microarray expression profiles (GSE48000 and GSE19151) were downloaded from the Gene Expression Ominibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using limma package, and overlapping DEGs were identified form the above two expression profiles. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway enrichment analyses were performed by DAVID. Protein-protein interaction (PPI) network was constructed by using STRING and visualized with Cytoscape. Furthermore, module analysis plus centrality analysis of the PPI network were executed to identify the potential key genes. Finally, the pathway analysis was performed using GenCLiP 3.0. RESULTS: A total of 173 DEGs (125 upregulated and 48 downregulated) were identified. GO analysis demonstrated that DEGs were mainly enriched in viral life cycle, ribosome and structural constituent of ribosome. Meanwhile, KEGG pathway analysis showed that these genes were enriched in ribosome, Parkinson's disease and cell cycle. Additionally, one most significant module and 12 hub genes were found. Finally, 6 key genes, namely ISG15, RPS15A, MRPL13, ICT1, MRPL15 and RPLP0, with high centrality features were identified. These key genes were mainly involved in translation, metabolism of proteins and ribosome pathway. CONCLUSIONS: In summary, these 6 identified genes and correlated pathways should play an important role in VTE, which can provide new insight into the molecular mechanism, potential biomarkers and therapeutic targets associated with VTE.