Observation of the out-of-plane orbital antidamping-like torque.

The out-of-plane antidamping-like orbital torque fosters great hope for high-efficiency spintronic devices. Here we report experimentally the observation of out-of-plane antidamping-like torque that could be generated by z-polarized orbital current in ferromagnetic-metal/oxidized Cu (CuOx) bilayers, which is presented unambiguously by the magnetic field angle dependence of the spin-torque ferromagnetic resonance signal. The CuOx thickness dependence of the orbital torque ratios highlights that the interfacial effect would be responsible for the generation of orbital current. Besides that, the CuOx thickness dependence of the damping parameter further proves the observation of antidamping-like torque. This result contributes to enriching the orbital-related theory of the generation mechanism of the orbital torque.

[Clinical and genetic analysis of a Chinese patient with Alström syndrome].

OBJECTIVE: To explore the genetic etiology for a patient with Alström syndrome (ALMS) presenting as dilated cardiomyopathy. METHODS: A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20, 2021 was selected as the study subject. Clinical and laboratory examinations were carried out. Whole exome sequencing (WES) was employed for genetic testing, and candidate variants were validated by Sanger sequencing and pathogenicity analysis. RESULTS: The patient had a 14-year medical history characterized by dilated cardiomyopathy, complete atrioventricular block, visual impairment, sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes, hypertension, renal dysfunction, and paranoid delusions. Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene, namely c.6823C>T (p.Arg2275Ter) and c.9442_9445dup (p.Ser3149LysfsTer2). Sanger sequencing confirmed that they were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1_VeryStrong+PM2_Supporting+PM3+PP3, PVS1_VeryStrong+PM2_Supporting+PM3). Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously. CONCLUSION: The c.6823C>T (p.Arg2275Ter) and c.9442_9445dup (p.Ser3149LysfsTer2) compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient. Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.

The Role of Follicular Regulatory T Cells/Follicular Helper T Cells in Primary Immune Thrombocytopenia.

INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia. Herein, we sought to identify potential immune-related therapeutic targets in ITP. METHODS: The differentially expressed genes (DEGs) between ITP patients and controls in GSE43177 and PRJNA299534 were analyzed. The intersections of the two DEG groups were screened as common genes, and enrichment analysis was performed. Additionally, differential analysis of immune cell levels between ITP and controls was performed. Changes in the proportions of T follicular helper (Tfh) and follicular regulatory T (Tfr) cells in peripheral blood samples from ITP patients, ITP patients responding to therapy, and healthy controls were identified. The expression changes in B-cell lymphoma (Bcl)-6 and interleukin (IL)-21 were further evaluated. RESULTS: A total of 76 common genes were identified, and enrichment analysis found that these genes were mainly associated with neutrophil-mediated immunity, the MAPK signaling pathway, and the FOXO signaling pathway. Furthermore, we found different levels of Tfh cells in patients with ITP and controls. The level of Tfh cells in the peripheral blood is significantly increased in ITP patients and declines after responding to therapy. The Tfr/Tfh ratio was reduced in ITP patients and increased after responding to therapy. IL-21 and Bcl-6 were more highly expressed in ITP patients than in controls. CONCLUSION: We identified abnormally expressed genes in ITP related to immune-related biological functions. We further identified the changes in Tfh and Tfr cells during ITP treatment. This provides a rationale for immunotherapy in ITP patients.

Recombinant human thrombopoietin (rhTPO) of different dosing regimens for refractory/relapsed primary immune thrombocytopenia: a multicenter, randomized controlled trial and pharmacokinetics study.

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0-295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0-190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.

What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis.Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options.Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone.What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy.Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 × 10⁹/L) from baseline and attained the highest total response rate on day 14 (63.2%).30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days.All 4 regimens were safe and well-tolerated.What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed.

Genome-wide identification, new classification, expression analysis and screening of drought & heat resistance related candidates in the RING zinc finger gene family of bread wheat (Triticum aestivum L.).

BACKGROUND: RING (Really Interesting New Gene) zinc finger (RING-zf) proteins belong to an important subclass of zinc fingers superfamily, which play versatile roles during various developmental stages and in abiotic stress responses. Based on the conserved cysteine and histidine residues, the RING-zf domains are classified into RING-HC (C3HC4), RING-H2 (C3H2C3), RING-v, RING-D, RING-S/T, RING-G, and RING-C2. However, little is known about the function of the RING-zfs of wheat. RESULTS: In this study, 129 (93.5%) of 138 members were found in nucleus, indicating TaRING-zf were primarily engaged in the degradation of transcription factors and other nuclear-localized proteins. 138 TaRING-zf domains can be divided into four canonical or modified types (RING-H2, RING-HC, RING-D, and RING-M). The RING-M was newly identified in T. aestivum, and might represent the intermediate other states between RING-zf domain and other modified domains. The consensus sequence of the RING-M domain can be described as M-X2-R-X14-Cys-X1-H-X2-Cys-X2-Cys-X10-Cys-X2-Cys. Further interspecies collinearity analyses showed that TaRING-zfs were more closely related to the genes in Poaceae. According to the public transcriptome data, most of the TaRING-zfs were expressed at different 15 stages of plant growth, development, and some of them exhibited specific responses to drought/heat stress. Moreover, 4 RING-HC (TraesCS2A02G526800.1, TraesCS4A02G290600.1, TraesCS4B02G023600.1 and TraesCS4D02G021200.1) and 2 RING-H2 (TraesCS3A02G288900.1 and TraesCS4A02G174600.1) were significantly expressed at different development stages and under drought stress. These findings provide valuable reference data for further study of their physiological functions in wheat varieties. CONCLUSIONS: Taken together, the characterization and classifications of the TaRING-zf family were extensively studied and some new features about it were revealed. This study could provide some valuable targets for further studies on their functions in growth and development, and abiotic stress responses in wheat.

Lectin receptor-like kinase LecRK-VIII.2 is a missing link in MAPK signaling-mediated yield control.

The energy allocation for vegetative and reproductive growth is regulated by developmental signals and environmental cues, which subsequently affects seed output. However, the molecular mechanism underlying how plants coordinate yield-related traits to control yield in changing source-sink relationships remains largely unknown. Here, we discovered the lectin receptor-like kinase LecRK-VIII.2 as a specific receptor-like kinase that coordinates silique number, seed size, and seed number to determine seed yield in Arabidopsis (Arabidopsis thaliana). The lecrk-VIII.2 mutants develop smaller seeds, but more siliques and seeds, leading to increased yield. In contrast, the plants overexpressing LecRK-VIII.2 form bigger seeds, but less siliques and seeds, which results in similar yield to that of wild-type plants. Interestingly, LecRK-VIII.2 promotes the growth of the rosette, root, and stem by coordinating the source-sink relationship. Additionally, LecRK-VIII.2 positively regulates cell expansion and proliferation in the seed coat, and maternally controls seed size. The genetic and biochemical analyses demonstrated that LecRK-VIII.2 acts upstream of the mitogen-activated protein kinase (MAPK) gene MPK6 to regulate silique number, seed size, and seed number. Collectively, these findings uncover LecRK-VIII.2 as an upstream component of the MAPK signaling pathway to control yield-related traits and suggest its potential for crop improvement aimed at developing plants with stable yield, a robust root system, and improved lodging resistance.

The specific DNA barcodes based on chloroplast genes for species identification of Theaceae plants.

More than 600 species in over 40 genera have been identified in family Theaceae worldwide. The accurate identification of Theaceae plants can ensure the market economic order, and it plays a vital role in achieving the sustainable utilization of germplasm resources. DNA barcoding, one of the most potential species identification technologies at present, has advanced in the rapid, accurate and repetitive discrimination of species. In this study, matK + ndhF + ycf1 was observed as the optimal combined candidate gene sequence of DNA barcodes by analyzing genetic information of four single chloroplast DNA sequences, including matK, rbcL, ndhF and ycf1, as well as six combined gene sequences. Subsequently, the experiments were performed on phylogenetic analysis based on genetic distance to study the phylogenetic relationship of Theaceae plants and evaluate the species identification accuracy of matK + ndhF + ycf1. Lastly, the species-specific DNA barcodes were designed by searching the variable sites (one type of single nucleotide polymorphism sites) for the accurate identification of Camellia amplexicaulis, Franklinia alatamaha, Gordonia brandegeei and Stewartia micrantha. The previous methods of screening and testing candidate gene sequences were optimized, and innovation was made in the above methods. The process of making visual DNA barcodes was standardized. Besides, DNA barcoding technology increased the accuracy of species identification and DNA barcoding was analyzed in accordance with the theories of population genetics (e.g., neutral theory of molecular evolution). The results of the study will lay a basis for the identification and protection of Theaceae species and germplasm resources. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01175-7.

Comprehensive genomic survey, structural classification and expression analysis of C2H2-type zinc finger factor in wheat (Triticum aestivum L.).

BACKGROUND: The C2H2-type zinc finger proteins (C2H2-ZFPs) are one of major classes of transcription factors that play important roles in plant growth, development and stress responses. Limit information about the C2H2-ZF genes hinders the molecular breeding in bread wheat (Triticum aestivum). RESULTS: In this study, 457 C2H2-ZFP proteins (including 253 splice variants), which contain four types of conserved domain (named Q, M, Z, and D), could be further classified into ten subsets. They were identified to be distributed in 21 chromosomes in T. aestivum. Subset-specific motifs, like NPL-, SFP1-, DL- (EAR-like-motif), R-, PL-, L- and EK-, might make C2H2-ZFP diverse multifunction. Interestingly, NPL- and SFP1-box were firstly found to be located in C2H2-ZFP proteins. Synteny analyses showed that only 4 pairs of C2H2 family genes in T. aestivum, 65 genes in B. distachyon, 66 genes in A. tauschii, 68 genes in rice, 9 genes in Arabidopsis, were syntenic relationships respectively. It indicated that TaZFPs were closely related to genes in Poaceae. From the published transcriptome data, totally 198 of 204 TaC2H2-ZF genes have expression data. Among them, 25 TaC2H2-ZF genes were certificated to be significantly differentially expressed in 5 different organs and 15 different development stages by quantitative RT-PCR. The 18 TaC2H2-ZF genes were verified in response to heat, drought, and heat & drought stresses. According to expression pattern analysis, several TaZFPs, like Traes_5BL_D53A846BE.1, were not only highly expressed in L2DAAs, RTLS, RMS, but also endowed tolerance to drought and heat stresses, making them good candidates for molecular breeding. CONCLUSIONS: This study systematically characterized the TaC2H2-ZFPs and their potential roles in T. aestivum. Our findings provide new insights into the C2H2-ZF genes in T. aestivum as well as a foundation for further studies on the roles of TaC2H2-ZF genes in T. aestivum molecular breeding.

Cell membrane proteins with high N-glycosylation, high expression and multiple interaction partners are preferred by mammalian viruses as receptors.

MOTIVATION: Receptor mediated entry is the first step for viral infection. However, the question of how viruses select receptors remains unanswered. RESULTS: Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors are structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. This study could deepen our understanding of virus-receptor interaction. AVAILABILITY AND IMPLEMENTATION: The database of mammalian virus-host receptor interaction is available at http://www.computationalbiology.cn: 5000/viralReceptor. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

High-dose dexamethasone plus recombinant human thrombopoietin vs high-dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective, multicenter, randomized trial.

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.

Prophylactic Use of Mucosal Protective Agents and Proton Pump Inhibitors in Patients Undergoing Percutaneous Coronary Intervention: Real World Evidences of 36,870 Patients.

BACKGROUND: Prophylactic medications are believed to reduce risks of gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI). However, their true effectiveness in preventing GI bleeding is still unknown. METHODS: The clinical data of 36,870 patients treated with PCI from January 2010 to July 2017 were retrospectively analyzed. The trend in the prophylactic use of mucosal protective agents and proton pump inhibitors was analyzed. RESULTS: A total of 36,870 patients were included with a mean age of 60 ± 18 years. In patients treated with primary PCI for ST-segment elevation myocardial infarction, prophylactic medications were associated with a significantly lower incidence of postprocedure GI bleeding in comparison with no medication (1.072%, 52/4852 vs. 2.747%, 25/910; P < 0.001). In patients with CRUSADE scores >40, prophylactic medications were associated with a significantly lower incidence of postprocedure GI bleeding in comparison with not using prophylactic medications (0.679%, 21/3093 vs. 1.899%, 20/1053; P = 0.001). CONCLUSIONS: Prophylactic medications were associated with significantly lower incidence of postprocedure 30-day GI bleeding in patients with primary PCI for ST-segment elevation myocardial infarction or CRUSADE scores >40.

Quantitative phosphoproteomics of lectin receptor-like kinase VI.4 dependent abscisic acid response in Arabidopsis thaliana.

Lectin receptor-like kinases (LecRKs) play important roles in the responses to adverse environment stress. Abscisic acid (ABA) is a plant hormone involved in plant growth, development and adverse environmental stress responses. Although some studies of ABA response LecRK genes have been reported, the molecular mechanisms of LecRKs regulation of downstream pathways under ABA induction are not well understood. The present study showed that LecRK-VI.4 responded to ABA and negatively regulated stomatal closure. Here, a quantitative phosphoproteomics approach based on mass spectrometry was employed to study the roles of LecRK-VI.4 in the ABA signaling pathway. Metal oxide affinity beads and C18 chromatography were used for phosphopeptide enrichment and separation. The isobaric tags for relative and absolute quantitation were used for profiling the phosphoproteome of mutant lecrk-vi.4-1 and wild-type Col-0 Arabidopsis under normal growth conditions or ABA treatments. In total, 475 unique phosphopeptides were quantified, including 81 phosphopeptides related to LecRK-VI.4 regulation. Gene ontology, protein-protein interaction and motif analysis were performed. The bioinformatics data showed that phosphorylated proteins regulated by LecRK-VI.4 had close relations with factors of stomatal function, which included aquaporin activity, H+ pump activity and the Ca2+ concentration in the cytoplasm. These data have expanded our understanding of how LecRK-VI.4 regulates ABA-mediated stomatal movements.

Pretreatment with Tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia/reperfusion injury via AMPK/SIRT1/PGC-1 alpha signaling pathway.

Mitochondrial energy metabolism and oxidative stress play a crucial role in ameliorating myocardial ischemia/reperfusion injury (MIRI). Tilianin has been reported to have a significant protection for mitochondrion in MIRI. However, the underlying mechanisms remain unknown. This study investigated whether Tilianin regulates mitochondrial energy metabolism and oxidative stress in MIRI via AMPK/SIRT1/PGC-1 alpha signaling pathway. The MIRI model was established by 30 min of coronary occlusion followed by 2 h of reperfusion in rats. The results revealed that Tilianin significantly reduced myocardial infarction, improved the pathological morphology of myocardium, markedly increased the contents of ATP and NAD+, decreased ADP and AMP contents and the ratio of AMP/ATP, reduced the level of ROS and MDA, enhanced SOD activity, evidently increased the levels of AMPK, SIRT1 and PGC-1 alpha mRNA, up-regulated the expressions of AMPK, pAMPK, SIRT1, PGC-1alpha, NRF1, TFAM and FOXO1 proteins. However, these effects were respectively abolished by Compound C (a specific AMPK inhibitor) and EX-527 (a specific SIRT1 inhibitor). Taken together, this study found that Tilianin could attenuate MIRI by improving mitochondrial energy metabolism and reducing oxidative stress via AMPK/SIRT1/PGC-1 alpha signaling pathway.

Differences in safety and efficacy of oral anticoagulants in patients with non-valvular atrial fibrillation: A Bayesian analysis.

BACKGROUND: Novel oral anticoagulants are the cornerstone of therapy for non-valvular atrial fibrillation patients to lower the risk of ischaemic stroke. Given the lack of head-to-head comparisons among oral anticoagulants, a Bayesian analysis was used to evaluate their safety and efficacy based on studies from real-world practice. METHODS: The PubMed, Embase, Cochrane and Web of Science databases were searched for relevant studies. Bayesian analyses were conducted to estimate hazard ratios (HR) and 95% credible intervals (CrI) for the safety and efficacy of oral anticoagulants. RESULTS: In the 22 studies included in our analysis, novel oral anticoagulants exhibited a clear advantage over warfarin in preventing ischaemic stroke, haemorrhagic stroke and, especially, intracranial haemorrhage. Incidence of major bleeding was lowest for apixaban, followed by dabigatran, warfarin and rivaroxaban. Gastrointestinal bleeding risk was lowest for apixaban, followed by warfarin, and was slightly lower for dabigatran than for rivaroxaban with no statistical difference (HR 1.05, 95% CrI 0.99-1.11). Ischaemic stroke risk was lowest for rivaroxaban, followed by apixaban, dabigatran and warfarin (HR 1.13, 95% CrI 1.07-1.20). CONCLUSION: In real-world practice, apixaban may represent the optimal treatment in terms of safety and efficacy for patients with non-valvular atrial fibrillation. For patients with high risk of ischaemic events but low bleeding risk, rivaroxaban may be preferable.

PEG-PCL modification and intestinal sustained-release of solid lipid nanoparticles for improving oral bioavailability of 2-methoxyestradiol.

The primary purpose of the present study was to design and optimize a solid lipid nanoparticle (SLN) formulation of the poorly water-soluble drug 2-methoxyestradiol (2-ME) to improve its oral bioavailability and prolong the duration of therapeutic drug level. SLN was modified by amphipathic PEG-PCL (PLN) and then encapsulated in pH-sensitive microparticles (MP) by spray drying technology. Several properties of 2-ME PLN-MP were characterized including particle size, drug loading, and drug or PLN release. After oral administration of 2-ME PLN-MP, retention time in mice was evaluated by in vivo imaging technology and the pharmacokinetic parameters in rats were determined by HPLC. The results demonstrated that PEG-PCL modification of 2-ME SLN significantly decreased particle size and delayed drug release without influencing IC50 in 4T1 cells. 2-ME PLN in the microparticles showed significant pH-sensitive release in the simulated gastrointestinal fluid and controlled release in the intestine. The PLN (labelled with IR-780 iodide) prolonged significantly fluorescence duration time compared to the SLN and the prolongation was further enhanced by the PLN-MP formulation. Furthermore, compared with the suspension, the PLN-MP formulation showed a 56.66-fold delay in Tmax, a 10.36-fold extension in MRT and a 140.86-fold increase in the relative bioavailability in the rat. The research work in the paper suggests that the PLN-MP could serve as a practical oral preparation for 2-ME in future cancer therapy.

Inheritance of Virulence, Construction of a Linkage Map, and Mapping Dominant Virulence Genes in Puccinia striiformis f. sp. tritici Through Characterization of a Sexual Population with Genotyping-by-Sequencing.

Puccinia striiformis f. sp. tritici, the wheat stripe rust pathogen, is a dikaryotic, biotrophic, and macrocyclic fungus. Genetic study of P. striiformis f. sp. tritici virulence was not possible until the recent discovery of Berberis spp. and Mahonia spp. as alternate hosts. To determine inheritance of virulence and map virulence genes, a segregating population of 119 isolates was developed by self-fertilizing P. striiformis f. sp. tritici isolate 08-220 (race PSTv-11) on barberry leaves under controlled greenhouse conditions. The progeny isolates were phenotyped on a set of 29 wheat lines with single genes for race-specific resistance and genotyped with simple sequence repeat (SSR) markers, single nucleotide polymorphism (SNP) markers derived from secreted protein genes, and SNP markers from genotyping-by-sequencing (GBS). Using the GBS technique, 10,163 polymorphic GBS-SNP markers were identified. Clustering and principal component analysis grouped these markers into six genetic groups, and a genetic map, consisting of six linkage groups, was constructed with 805 markers. The six clusters or linkage groups resulting from these analyses indicated a haploid chromosome number of six in P. striiformis f. sp. tritici. Through virulence testing of the progeny isolates, the parental isolate was found to be homozygous for the avirulence loci corresponding to resistance genes Yr5, Yr10, Yr15, Yr24, Yr32, YrSP, YrTr1, Yr45, and Yr53 and homozygous for the virulence locus corresponding to resistance gene Yr41. Segregation was observed for virulence phenotypes in response to the remaining 19 single-gene lines. A single dominant gene or two dominant genes with different nonallelic gene interactions were identified for each of the segregating virulence phenotypes. Of 27 dominant virulence genes identified, 17 were mapped to two chromosomes. Markers tightly linked to some of the virulence loci may facilitate further studies to clone these genes. The virulence genes and their inheritance information are useful for understanding the host-pathogen interactions and for selecting effective resistance genes or gene combinations for developing stripe rust resistant wheat cultivars.

Patients with symptoms and characteristics consistent with obstructive sleep apnea are at a higher risk for acute and subacute stent thrombosis after percutaneous coronary stent implantation: a single-center case-control study.

BACKGROUND: To determine if obstructive sleep apnea (OSA) is a risk factor for early stent thrombosis (EST; within 30 days) after percutaneous coronary intervention (PCI). METHODS: This case-control study involved 23 patients with angiographically confirmed EST after PCI (case group) and 92 PCI patients (control group) who did not develop stent thrombosis during a 2-year follow-up. Patients with symptoms and characteristics consistent with OSA (hereinafter referred to as OSA) were identified using the Berlin questionnaire, and the general characteristics of the patients and their treatments as well as outcomes were recorded. The odds ratios (ORs) for OSA were calculated. Additionally, the association between OSA and EST in patients with different conventional cardiovascular risk factors was analyzed. RESULTS: The crude OR for OSA was 4.17 (95% confidence interval [CI]: 1.60-10.84, P = 0.003). After adjusting for other risk factors of EST, the OR for OSA remained significant. In participants with no or one conventional cardiovascular disease risk factor, we found a significant association between OSA and EST (OR: 17.00, 95% CI: 2.33-124.19, P = 0.005). CONCLUSION: OSA is an independent risk factor for EST. This conclusion was further supported by the finding that in patients with few conventional cardiovascular risk factors, the contribution of OSA to EST was more obvious.

Tilianin Post-Conditioning Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondrial Protection and Inhibition of Apoptosis.

BACKGROUND The aim of this study was to investigate the role of tilianin in modulating mitochondrial functions and mitochondria-mediated apoptosis during cardio-protection. MATERIAL AND METHODS Myocardial ischemia/reperfusion (I/R) injury was induced by 30 minutes coronary occlusion followed by two hours reperfusion in Sprague-Dawley rats. To investigate the cardio-protective effects of tilianin, apoptosis was evaluated by TUNEL. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy, dynamics of mitochondrial permeability transition pore (mPTP) opening and ATP production in the myocardium; Ca2+ content and reactive oxygen species (ROS) were measured to evaluated the level of damage factors in the mitochondria. The related apoptotic proteins were analyzed through immunoblot. RESULTS Pretreatment with tilianin significantly reduced apoptosis after I/R injury in rats (p<0.05). In addition, tilianin could alleviate mitochondrial damage, markedly inhibited mPTP opening and improved ATP production (p<0.05). There was also a significant reduction for content of Ca2+ and ROS in the mitochondria (p<0.01). Apoptosis protein analysis found that treatment with tilianin led to the downregulation of apoptosis-inducing factor (AIF) (p<0.01), and suppressed the leakage of cytochrome c and activation of caspase-3 (p<0.05). CONCLUSIONS This study showed that tilianin can alleviate apoptosis of cardiomyocytes and protect myocardium, possibly via the protection of mitochondria and repression of mitochondrial apoptotic pathways. Mechanistically, inhibition of Ca2+ overload, mPTP opening, and ROS production in mitochondria may explain the observed tilianin-mediated treatment effects.

CKB1 is involved in abscisic acid and gibberellic acid signaling to regulate stress responses in Arabidopsis thaliana.

Casein kinase II (CK2), an evolutionarily well-conserved Ser/Thr kinase, plays critical roles in all higher organisms including plants. CKB1 is a regulatory subunit beta of CK2. In this study, homozygous T-DNA mutants (ckb1-1 and ckb1-2) and over-expression plants (35S:CKB1-1, 35S:CKB1-2) of Arabidopsis thaliana were studied to understand the role of CKB1 in abiotic stress and gibberellic acid (GA) signaling. Histochemical staining showed that although CKB1 was expressed in all organs, it had a relatively higher expression in conducting tissues. The ckb1 mutants showed reduced sensitivity to abscisic acid (ABA) during seed germination and seedling growth. The increased stomatal aperture, leaf water loss and proline accumulation were observed in ckb1 mutants. In contrast, the ckb1 mutant had increased sensitivity to polyaluminum chloride during seed germination and hypocotyl elongation. We obtained opposite results in over-expression plants. The expression levels of a number of genes in the ABA and GA regulatory network had changed. This study demonstrates that CKB1 is an ABA signaling-related gene, which subsequently influences GA metabolism, and may play a positive role in ABA signaling.