Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. METHODS: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. FINDINGS: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. INTERPRETATION: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. FUNDING: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

Biological characterization of emerging fungal pathogen Colletotrichum associated with mango (Mangifera indica L.) post-harvest anthracnose from Vietnam.

BACKGROUND: Post-harvest anthracnose (PHA) of mango is a devastating disease, which results in huge loss to mango producers and importers. Various species of PHA, diverse pathogenicity, and different resistance towards fungicides make it essential to evaluate the pathogen taxonomic status and biological characterization. METHODS AND RESULTS: Two strains DM-1 and DM-2 isolated from the fruit of DaQing mango from Vietnam were identified as Colletotrichum fructicola and C. asianum respectively, based on the morphological features, along with the phylogenetic tree of ITS and ApMat combined sequences. The growth status of different Colletotrichum strains under different conditions was analyzed to reveal the biological characteristics. The optimum growth temperature of DM-1 and DM-2 was 28 °C and mycelia grew rapidly in the dark. Both strains could grow in media with pH 4-11, while the optimum pH value was 6. Maltose and soluble starch were the most suitable carbon source for DM-1 and DM-2 respectively, and the peptone was the most suitable nitrogen source for both strains. The lethal temperatures were recorded as 55 °C 5 min for DM-1, and 50 °C 10 min for DM-2. CONCLUSIONS: To the best of our knowledge, it is the first study reporting the identification of the pathogens: C. fructicola and C. asianum responsible for postharvest fruit anthracnose of mango in Vietnam.

Fengycin produced by Bacillus subtilis XF-1 plays a major role in the biocontrol of Chinese cabbage clubroot via direct effect and defense stimulation.

Bacillus subtilis XF-1 is a well-investigated biocontrol agent against the biotrophic Plasmodiophora brassicae Woron., the causal agent of clubroot disease of cruciferous crops. The present study demonstrates that XF-1 could efficiently control clubroot disease via leaf spraying and provides an understanding of the biocontrol mechanisms. High-performance thin-layer chromatography (HTPLC) analysis indicated the presence of fengycin-type cyclopeptides in the supernatant. A ppsB deletion mutant of XF-1 resulted in no fengycin production, significantly reduced the lysis rate of testing spores in vitro and the primary infection rate of root hair in vivo, and decreased the protection value against clubroot disease under the greenhouse conditions. Confocal laser scanning microscopy proved that fengycin was not required for leaf internalization and root colonization. Moreover, the expression level of the ppsB gene in XF-1 was regulated by its cell density in root during interaction with P. brassicae. In addition, the ΔppsB mutant of XF-1 could not efficiently control disease because it led to a lower activation level of the jasmonic acid and salicylic acid signaling pathways in roots, which are necessary for the plant defense reaction upon pathogen invasion. Altogether, the present study provides a new understanding of specific cues in the interaction between B. subtilis and P. brassicae as well as insights into the application of B. subtilis in agriculture.

Complementary evidence on the performance of coronary stents generated by a randomized controlled trial and a worldwide registry.

BACKGROUND: Large-scale registries can provide valuable complementary data to randomized controlled trials (RCT) for the postmarketing evaluation of coronary stents, but their scientific relevance remains debated. METHODS: We sought to compare the evidence on the performance of a single coronary stent platform generated by the RCT for its regulatory approval and a well-conducted international registry. Patients treated with the Ultimaster coronary stent in the CENTURY II (CII-UM) trial (n = 551) were compared to patients in the real-world e-ULTIMASTER (e-UM) registry (n = 35,389). All major events were adjudicated by an independent clinical event committee in both studies. Propensity weighted analysis was used to balance baseline and procedural differences between the 2 populations. RESULTS: Coronary artery disease was more complex in e-UM compared to CII-UM, including more acute coronary syndromes, multivessel disease, left main, arterial, or venous grafts, and chronic total occlusions (P < .005 for all). At one-year follow-up and after excluding periprocedural myocardial infarction (MI) there was no statistically significant difference between CII-UM and e-UM regarding all-cause death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.26-1.20, P = .14), cardiac death (HR 0.71, 95% CI 0.29-1.72, P = .45), target lesion failure (HR 1.18, 95% CI 0.78-1.78, P = .44), and target vessel MI (HR 0.76, 95% CI 0.24-2.38, P = .63). However, target vessel revascularization rate was significantly higher in CII-UM than in e-UM, HR 1.78, 95% CI 1.23-2.56, P = .002. CONCLUSIONS: A well-conducted large-scale registry can provide valuable complementary evidence to RCTs on the postmarket performance of new coronary stents, across a wider range of uses and various geographic areas.

Biocontrol of plant pathogens in omics era-with special focus on endophytic bacilli.

Nearly all plants and their organs are inhabited by endophytic microbes which play a crucial role in plant fitness and stress resilience. Harnessing endophytic services can provide effective solutions for a sustainable increase in agriculture productivity and can be used as a complement or alternative to agrochemicals. Shifting agriculture practices toward the use of nature-based solutions can contribute directly to the global challenges of food security and environmental sustainability. However, microbial inoculants have been used in agriculture for several decades with inconsistent efficacy. Key reasons of this inconsistent efficacy are linked to competition with indigenous soil microflora and inability to colonize plants. Endophytic microbes provide solutions to both of these issues which potentially make them better candidates for microbial inoculants. This article outlines the current advancements in endophytic research with special focus on endophytic bacilli. A better understanding of diverse mechanisms of disease control by bacilli is essential to achieve maximum biocontrol efficacy against multiple phytopathogens. Furthermore, we argue that integration of emerging technologies with strong theoretical frameworks have the potential to revolutionize biocontrol approaches based on endophytic microbes.

First report of Aloe root and stem rot caused by Phytophthora palmivora in Yunnan Province, China.

Aloe genus plants are perennial evergreen herb belonging to Liliaceae family which is widely used in food, medicine, beauty, and health care (Kumar et al. 2019). In August 2021, symptoms of root and stem rot was observed in approximately 20% of Aloe vera plantings in Yuanjiang County, Yunnan Province, China (23° 64' 53" N, 101° 99' 84" E). The most typical symptoms were stem and root rot, browning and necrosis of vascular tissues, gradual greening, and reddish-browning of leaves from bottom to top, abscission, and eventual plant death (Fig. S1). Therefore, to isolate and identify the pathogen, the plants showing the above symptoms were collected. The plant tissues were cut from the edges of root and stem lesions, followed by disinfection with 75% ethanol for 1 min, rinsed three times with sterilized distilled water, and cut into 3 × 3 mm small squares after excision of marginal tissues. The tissues were transferred to the oomycetes selective medium (Liu et al. 2022) and incubated at 28 °C in the dark for 3~5 days, and suspected colonies were purified. The colonies were then inoculated onto potato dextrose agar (PDA), V8-juice agar (V8), and oatmeal agar (OA) medium plates for morphological characteristics. Finally, 18 isolates with the same colonial and morphological characteristics were obtained from 30 lesioned tissue and one of them was named as ARP1. On PDA, V8 and OA medium plates, the ARP1 colonies were white. On PDA plate, the mycelia were dense and the colonies were petal-like; on V8 plate, the mycelia were cashmere and the colonies were radial or star-like. Whereas, on OA plate, the mycelia were cotton-like and the colonies were fluffy and radial (Fig. S2 A~C). Mycelium did not have septum with high branching and swelling. Sporangia were abundant, semi-papillate, varying in shape from ovoid-ellipsoid to long-ellipsoid, 18-26 × 45-63 µm (average: 22 × 54 µm, n = 30), sporangia released numerous zoospores from the papillate after maturation. The chlamydospores were spherical, 20-35 µm in diameter (average: 27.5 µm, n = 30) (Fig. S2 D~F). These morphological features were like those of the pathogenic species of the oomycetes (Chen et al. 2022). For the molecular characterization, the genomic DNA of the isolate was extracted using the cetyl trimethyl ammonium bromide method, and the translation elongation factor 1α (tef-1α) (Stielow et al. 2015), ß-tubulin (ß-tub) (Kroon et al. 2004) and internal transcribed spacer (ITS) (White et al. 1990) of isolated strain ARP1 were amplified using primer pairs EF1-1018F/EF1-1620R, TUBUF2/TUBUR1 and ITS1/ITS4, respectively. The tef-1α, ß-tub genes and ITS region of ARP1 were directly sequenced and their sequence information was deposited in GenBank under accession numbers OQ506129, OQ506127 and OQ449628. ARP1 was clustered on the same evolutionary branch with Phytophthora palmivora (Fig. S3). To confirm the pathogenicity of ARP1, the main root of A. vera was wounded to 1 cm long and 2 mm deep with a scalpel blade followed by inoculation with 50 ml suspension of ARP1 zoospores at a concentration of 1 × 106 spores / ml per potted plant, and an equal volume of water as control. All inoculated plants were placed in the greenhouse at 28°C, 12 h / 12 h light / dark. After 15 dpi, the inoculated plants showed typical symptoms of wilted and drooping leaves and stem and root rot, same as observed in the field condition (Fig. S4). After inoculation with ARP1, a strain with the same morphological and molecular characteristics as the original isolate was re-isolated, confirming Koch's postulates. To our knowledge, this is the first report of P. palmivora causing root and stem rot of A. vera in the study region. This disease could be a potential risk for aloe production and therefore appropriate management measures should be taken.

Bacillus amyloliquefaciens AK-12 Helps Rapeseed Establish a Protection against Brevicoryne brassicae.

Aphids are a serious threat to rapeseed (Brassica napus L.) production, and cause unmanageable loss. Therefore, effective prevention and management strategies are urgently required to avoid losses. Bacillus amyloliquefaciens AK-12 isolated from a dead aphid with aphicidal activity was tagged with a green fluorescent protein through a natural transformation. The transformed strains were checked for stability and growth, and the best-performing strain was tested for its colonization inside and outside the rapeseed plant. The stability of AK-12-GFP reached more than 95%, and the growth curve was consistent with that of AK-12. After 30 days of treatment, the colonization of 1 × 106 CFU/g was recorded in rapeseed leaves. Interestingly, AK-12 reduced the aphid transmission rate compared with the control and improved the growth of the rapeseed seedlings. Meanwhile, the AK-12 strain also exhibited phosphorus, potassium-solubilizing, and nitrogen-fixing activity, and produced 2.61 µg/mL of IAA at 24 h. Regulation in the activity of four enzymes was detected after the AK-12 treatment. Phenylalanine ammonia lyase (PAL) was recorded at a maximum of 86.84 U/g after 36 h, and catalase (CAT) decreased after 48 h; however, peroxidase (POD) and polyphenol oxidase (PPO) reached the maximum within 12 h of AK-12 application. Additionally, important resistance genes related to these enzymes were upregulated, indicating the activation of a defense response in the rapeseed against aphids. In conclusion, defense enzymes and defense-related gene activation could improve the pest resistance in rapeseed, which has good application prospects for the future to be developed into biopesticide.

The hidden treasures of citrus: finding Huanglongbing cure where it was lost.

Huanglongbing (HLB), a deadly citrus disease which has significantly downsized the entire industry worldwide. The intractable and incurable disease has brought the citriculture an enormous loss of productivity. With no resistant varieties available, failure of chemical treatments despite repeated applications, and hazardous consequences to environmental health, have led to large-scale research to find a sustainable cure. Inside plants, the key determinants of health and safety, live the endophytic microbes. Endophytes possess unrivaled plant benefiting properties. The progression of HLB is known to cause disturbance in endophytic bacterial communities. Given the importance of the plant endophytic microbiome in disease progression, the notion of engineering microbiomes through indigenous endophytes is attracting scientific attention which is considered revolutionary as it precludes the incompatibility concerns associated with the use of alien (microbes from other plant species) endophytes. In this review, we briefly discuss the transformation of the plant-pathogen-environment to the plant-pathogen-microbial system in a disease triangle. We also argue the employment of indigenous endophytes isolated from a healthy state to engineer the diseased citrus endophytic microbiomes that can provide sustainable solution for vascular pathogens. We evaluated the plethora of microbiomes responses to the re-introduction of endophytes which leads to disease resistance in the citrus host. The idea is not merely confined to citrus-HLB, but it is globally applicable for tailoring a customized cure for general plant-pathogen systems particularly for the diseases caused by the vascular system-restricted pathogens.

Phytophthora cinnamomi causing root rot on Rhododendron lapponicum and control it using potential biocontrol agents.

Rhododendron lapponicum (R. lapponicum) is a dwarf Rhododendron species, which is severely infected with root rot and wilt in Yunnan province, China. However, the causal agent causing these symptoms was unknown. An isolate, Pci-1 was identified as Phytophthora cinnamomi, based on its morphology and the sequences of ß-tubulin, internal transcribed spacer, and Ypt1 genes and verified according to the Koch's postulate. We found that this pathogen could infect 14 species of plants, including Althaea rosea, Viburnum cylindricum, and Brassica napus. Strain Pci-1 could cause R. lapponicum to wither and die; and it grows best in an oat medium with pH 7.0 - 8.0 and an optimum temperature of 27°C. We suggest that the rhizosphere of R. lapponicum treated with biocontrol strains Paenibacillus polymyxoides P2-5 and Trichoderma asperellum Tv-1 showed a significant inhibitory effect on pathogen Pci-1. The inhibitory effect of 70% dimethomorph + cymoxanil was significantly higher with EC50 and EC90 values of 0.1894 and 0.3618 a.i. µg/ml, respectively. Greenhouse experiments revealed that the pathogen load is decreased in the presence of potential antagonists. This study provides fundamentals on risk assessment and theoretical support for the management of P. cinnamomi pathogen and contributes significantly to the planting of forest and horticultural crops in a disease-free environment.

Novel Virulence Factors Deciphering Klebsiella pneumoniae KpC4 Infect Maize as a Crossing-Kingdom Pathogen: An Emerging Environmental Threat.

Klebsiella pneumoniae is not only a human and animal opportunistic pathogen, but a food-borne pathogen. Cross-kingdom infection has been focused on since K. pneumoniae was identified as the pathogen of maize, banana, and pomegranate. Although the pathogenicity of K. pneumoniae strains (from ditch water, maize, and human) on plant and mice has been confirmed, there are no reports to explain the molecular mechanisms of the pathogen. This study uncovered the K. pneumoniae KpC4 isolated from maize top rot for the determination of various virulence genes and resistance genes. At least thirteen plant disease-causing genes are found to be involved in the disruption of plant defense. Among them, rcsB is responsible for causing disease in both plants and animals. The novel sequence types provide solid evidence that the pathogen invades plant and has robust ecological adaptability. It is imperative to perform further studies on the verification of these KpC4 genes' functions to understand the molecular mechanisms involved in plant−pathogen interactions.

Diversity of transcription activator-like effectors and pathogenicity in strains of Xanthomonas oryzae pv. oryzicola from Yunnan.

The present study aimed to evaluate transcriptional activator-like effector (TALE) genes in 86 Xanthomonas oryzae pv. oryzicola strains collected from 8 rice-growing regions in Yunnan, and to examine the relationship between TALE genotypes and virulence in 6 differential rice lines. Besides, the geographical areas, distribution of these genotypes were studied in detail. Genetic diversity was analyzed through the number and size of putative TALE genes based on TALE gene avrXa3 as a probe. We found that X. oryzae pv. oryzicola strains consist of variable number (13-27) of avrXa3-hybridizing fragments (putative TALE genes). Test strains were classified into 8 genotypes (G1-G8) with major genotypes G3 and G7 widely distributed in Yunnan. Pathogenicity of X. oryzae pv. oryzicola was evaluated by inoculating 6 differential rice lines with a single resistance gene into 9 pathotypes clusters (I-IX), the dominant Genotypes G3 and G7 consist of pathotypes I, II, and IV. Furthermore, we also detected the known TALE target genes expression in susceptible rice cultivar (cv. nipponbare) after inoculating 8 genotypes-representative X. oryzae pv. oryzicola strain. Correlation between the numbers of putative TALE genes of X. oryzae pv. oryzicola and relevant target genes in nipponbare confirmed up-regulation. Altogether, this study has given insights into the population structure of X. oryzae pv. oryzicola that may inform strategies to control BLS in rice.

Ecology and etiology of bacterial top rot in maize caused by Klebsiella pneumoniae KpC4.

Klebsiella pneumoniae is an important opportunistic pathogen in humans and animals. Recently, K. pneumoniae KpC4 was identified as a causative agent of bacterial top rot in maize, which has been observed in many areas of Yunnan province, China. KpC4 is potentially dangerous to humans and livestock due to its cross-kingdom infection ability. Our study revealed the disease cycle of maize bacterial top rot caused by KpC4 and the ecological adaptability and host range of KpC4. We found same pathogenicity in maize between KpC4, the environmental strains E1, E4 (K1 serotype), E5, and the clinical strain K. pneumoniae 138 (Kp138). Alternative hosts of K. pneumoniae include not only humans and animals but also a variety of plants (such as maize, banana and sorghum). One of the survival strategies of K. pneumoniae is ecological adaptability, which is an essential factor for KpC4 to be able to cause bacterial top rot in maize. K. pneumoniae, for example, could survive in large numbers (2.34 ± 0.22 × 103 cfu/g) not only in the maize leaves (2.34 ± 0.22 × 103 cfu/g) under natural light, but persist in dried maize plant debris (1.51 × 104 cfu/g) for at least 6 months. K. pneumoniae strains from different sources can generally induce infection in susceptible hosts. Thus, this study revealed the ecological basis of KpC4 cross-kingdom infections, laying the foundation for the study of the mechanisms underlying cross-kingdom infections involving this type of human/animal opportunistic pathogen.

Megaloblastic anaemia in a 9-weeks old infant: A case report.

Megaloblastic anaemia due to vitamin B12 and folic acid deficiency is uncommon in infancy and rarely reported in infants below 3 months of age. We hereby report a case of megaloblastic anaemia in a 9-weeks old infant having fever from 7th week of life. Blood picture showed pancytopenia and diagnosis was confirmed on bone marrow biopsy and serum level of vitamins. Patient positively responded to vitamin B12 and folic acid supplementation. Infants with pancytopenia even younger than 2 months, should also be investigated for vitamin B12 and folate deficiency. Mother of the baby was not antenatally investigated for anaemia. Prompt antenatal diagnosis and treatment of mothers can reduce the incidence in the infants.

Epidemiology of Cutaneous Leishmaniasis Outbreak, Waziristan, Pakistan.

During 2013-2015, prevalence of cutaneous leishmaniasis in war-affected Waziristan areas was 3.61% by PCR. Youths (1-15 years of age) were more susceptible. Internal transcribed spacer 1 PCR followed by restriction fragment length polymorphism analysis identified Leishmania tropica in 215 samples and Leishmania major in 6 samples.

Huanglongbing Control: Perhaps the End of the Beginning.

Huanglongbing (HLB) is one of the most destructive citrus plant diseases worldwide. It is associated with the fastidious phloem-limited α-proteobacteria 'Candidatus Liberibacter asiaticus', 'Ca. Liberibacter africanus' and 'Ca. Liberibacter americanus'. In recent years, HLB-associated Liberibacters have extended to North and South America. The causal agents of HLB have been putatively identified, and their transmission pathways and worldwide population structure have been extensively studied. However, very little is known about the epidemiologic relationships of Ca. L. asiaticus, which has limited the scope of HLB research and especially the development of control strategies. HLB-affected plants produce damaged fruits and die within several years. To control the disease, scientists have developed new compounds and screened existing compounds for their antibiotic and antimicrobial activities against the disease. These compounds, however, have very little or even no effect on the disease. The aim of the present review was to compile and compare different methods of HLB disease control with newly developed integrative strategies. In light of recent studies, we also describe how to control the vectors of this disease and the biological control of other citrus plant pathogens. This work could steer the attention of scientists towards integrative control strategies.

Identification for the First Time of Cyclo(d-Pro-l-Leu) Produced by Bacillus amyloliquefaciens Y1 as a Nematocide for Control of Meloidogyne incognita.

The aim of the current study was to describe the role and mechanism of Bacillus amyloliquefaciens Y1 against the root-knot nematode, Meloidogyne incognita, under in vitro and in vivo conditions. Initially, the exposure of the bacterial culture supernatant and crude extract of Y1 to M. incognita significantly inhibited the hatching of eggs and caused the mortality of second-stage juveniles (J2), with these inhibitory effects depending on the length of incubation time and concentration of the treatment. The dipeptide cyclo(d-Pro-l-Leu) was identified in B. amyloliquefaciens culture for the first time using chromatographic techniques and nuclear magnetic resonance (NMR ¹H, 13C, H-H COSY, HSQC, and HMBC) and recognized to have nematocidal activity. Various concentrations of cyclo(d-Pro-l-Leu) were investigated for their effect on the hatching of eggs and J2 mortality. Moreover, the in vivo nematocidal activity of the Y1 strain was investigated by conducting pot experiments in which tomato plants were inoculated with M. incognita. Each and every pot was amended 50 mL of fertilizer media (F), or Y1 culture, or nematicide (N) (only once), or fertilizer media with N (FN) at 1, 2, 3, 4 and 5 weeks after transplantation. The results of the pot experiments demonstrated the antagonistic effect of B. amyloliquefaciens Y1 against M. incognita as it significantly decreases the count of eggs and galls per root of the tomato plant as well as the population of J2 in the soil. Besides, the investigation into the growth parameters, such as the length of shoot, shoot fresh and dry weights of the tomato plants, showed that they were significantly higher in the Y1 strain Y1-treated plants compared to F-, FN- and N-treated plants. Therefore, the biocontrol repertoire of this bacterium opens a new insight into the applications in crop pest control.

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.

BACKGROUND: Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. METHODS: In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518. FINDINGS: Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59). INTERPRETATION: Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. FUNDING: Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

P-hydroxybenzoic acid positively affect the Fusarium oxysporum to stimulate root rot in Panax notoginseng.

Background: Plant health is directly related to the change in native microbial diversity and changes in soil health have been implicated as one of the main cause of root rot. However, scarce information is present regarding allelopathic relationship of Panax notoginseng root exudates and pathogenic fungi Fusarium oxysporum in a continuous cropping system. Methods: We analyzed P. notoginseng root exudate in the planting soil for three successive years to determine phenolic acid concentration using GC-MS and HPLC followed by effect on the microbial community assembly. Antioxidant enzymes were checked in the roots to confirm possible resistance in P. notoginseng. Results: Total 29 allelochemicals in the planting soil extract was found with highest concentration (10.54 %) of p-hydroxybenzoic acid. The HPLC showing a year-by-year decrease in p-hydroxybenzoic acid content in soil of different planting years, and an increase in population of F. oxysporum. Moreover, community analysis displayed negative correlation with 2.22 mmol. L-1 of p-hydroxybenzoic acid correspond to an 18.1 % population of F. oxysporum. Furthermore, in vitro plate assay indicates that medium dose of p-hydroxybenzoic acid (2.5-5 mmol. L-1) can stimulate the growth of F. oxysporum colonies and the production of macroconidia, as well as cell wall-degrading enzymes. We found that 2-3 mmol. L-1 of p-hydroxybenzoic acid significantly increased the population of F. oxysporum. Conclusion: In conclusion, our study suggested that p-hydroxybenzoic acid have negative effect on the root system and modified the rhizosphere microbiome so that the host plant became more susceptible to root rot disease.

Bacillus subtilis YZ-1 surfactins are involved in effective toxicity against agricultural pests.

BACKGROUND: Insect pests negatively affect crop quality and yield. The excessive use of chemical pesticides has serious impacts on the environment and food safety. Therefore, development of effective management strategies in the form of bio-agents have important agricultural applications. Tenebrio molitor, a storage pest, causes losses of grains, medicinal materials, and various agricultural and related products in the warehouse. Bacillus subtilis YZ-1 isolated from naturally deceased Pieris rapae has been found to exhibit significant toxicity against T. molitor. RESULTS: Treatment with B. subtilis YZ-1 fermentation broth resulted in a 90-95% mortality rate of T. molitor within 36 h post-treatment, indicating some active substances may have insecticidal activity in the bacterial supernatant. A bioactivity-guided fractionation method was used to isolate the insecticidal compounds from YZ-1, which led to the identification of surfactins. Additionally, a surfactin deletion mutant YZ-1△srfAA was constructed and the surfactin production by the mutant YZ-1△srfAA was verified through liquid chromatography-mass spectrometry (LC-MS). Further, YZ-1△srfAA exhibited loss of insecticidal activity against T. molitor, Plutella xylostella and Achelura yunnanensis. The insecticidal activity and surfactins contents of several strains of Bacillus sp. were also tested and correlation was found between varying surfactins yield and insecticidal activity exhibited by different strains. CONCLUSION: Conclusively, our results suggest that B. subtilis YZ-1 may provide a novel approach for plant protection against agricultural pests. © 2023 Society of Chemical Industry.