CgCFEM1 Is Required for the Full Virulence of Colletotrichum gloeosporioides.

Colletotrichum gloeosporioides is widely distributed and causes anthracnose on many crops, resulting in serious economic losses. Common fungal extracellular membrane (CFEM) domain proteins have been implicated in virulence and their interaction with the host plant, but their roles in C. gloeosporioides are still unknown. In this study, a CFEM-containing protein of C. gloeosporioides was identified and named as CgCFEM1. The expression levels of CgCFEM1 were found to be markedly higher in appressoria, and this elevated expression was particularly pronounced during the initial stages of infection in the rubber tree. Absence of CgCFEM1 resulted in impaired pathogenicity, accompanied by notable perturbations in spore morphogenesis, conidiation, appressorium development and primary invasion. During the process of appressorium development, the absence of CgCFEM1 enhanced the mitotic activity in both conidia and germ tubes, as well as compromised conidia autophagy. Rapamycin was found to basically restore the appressorium formation, and the activity of target of rapamycin (TOR) kinase was significantly induced in the CgCFEM1 knockout mutant (∆CgCFEM1). Furthermore, CgCFEM1 was proved to suppress chitin-triggered reactive oxygen species (ROS) accumulation and change the expression patterns of defense-related genes. Collectively, we identified a fungal effector CgCFEM1 that contributed to pathogenicity by regulating TOR-mediated conidia and appressorium morphogenesis of C. gloeosporioides and inhibiting the defense responses of the rubber tree.

Roles of CgEde1 and CgMca in Development and Virulence of Colletotrichum gloeosporioides.

Anthracnose, induced by Colletotrichum gloeosporioides, poses a substantial economic threat to rubber tree yields and various other tropical crops. Ede1, an endocytic scaffolding protein, plays a crucial role in endocytic site initiation and maturation in yeast. Metacaspases, sharing structural similarities with caspase family proteases, are essential for maintaining cell fitness. To enhance our understanding of the growth and virulence of C. gloeosporioides, we identified a homologue of Ede1 (CgEde1) in C. gloeosporioides. The knockout of CgEde1 led to impairments in vegetative growth, conidiation, and pathogenicity. Furthermore, we characterized a weakly interacted partner of CgEde1 and CgMca (orthologue of metacaspase). Notably, both the single mutant ΔCgMca and the double mutant ΔCgEde1/ΔCgMca exhibited severe defects in conidiation and germination. Polarity establishment and pathogenicity were also disrupted in these mutants. Moreover, a significantly insoluble protein accumulation was observed in ΔCgMca and ΔCgEde1/ΔCgMca strains. These findings elucidate the mechanism by which CgEde1 and CgMca regulates the growth and pathogenicity of C. gloeosporioides. Their regulation involves influencing conidiation, polarity establishment, and maintaining cell fitness, providing valuable insights into the intricate interplay between CgEde1 and CgMca in C. gloeosporioides.

Zein-Based Triple-Drug Nanoparticles to Promote Anti-Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury.

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury.

Ralstonia solanacearum effector RipAK suppresses homodimerization of the host transcription factor ERF098 to enhance susceptibility and the sensitivity of pepper plants to dehydration.

Plants have evolved a sophisticated immune system to defend against invasion by pathogens. In response, pathogens deploy copious effectors to evade the immune responses. However, the molecular mechanisms used by pathogen effectors to suppress plant immunity remain unclear. Herein, we report that an effector secreted by Ralstonia solanacearum, RipAK, modulates the transcriptional activity of the ethylene-responsive factor ERF098 to suppress immunity and dehydration tolerance, which causes bacterial wilt in pepper (Capsicum annuum L.) plants. Silencing ERF098 enhances the resistance of pepper plants to R. solanacearum infection not only by inhibiting the host colonization of R. solanacearum but also by increasing the immunity and tolerance of pepper plants to dehydration and including the closure of stomata to reduce the loss of water in an abscisic acid signal-dependent manner. In contrast, the ectopic expression of ERF098 in Nicotiana benthamiana enhances wilt disease. We also show that RipAK targets and inhibits the ERF098 homodimerization to repress the expression of salicylic acid-dependent PR1 and dehydration tolerance-related OSR1 and OSM1 by cis-elements in their promoters. Taken together, our study reveals a regulatory mechanism used by the R. solanacearum effector RipAK to increase virulence by specifically inhibiting the homodimerization of ERF098 and reprogramming the transcription of PR1, OSR1, and OSM1 to boost susceptibility and dehydration sensitivity. Thus, our study sheds light on a previously unidentified strategy by which a pathogen simultaneously suppresses plant immunity and tolerance to dehydration by secreting an effector to interfere with the activity of a transcription factor and manipulate plant transcriptional programs.

Association of preoperative electrocardiographic markers with sepsis in elderly patients after general surgery.

BACKGROUND: Electrocardiographic markers, as surrogates for sympathetic excitotoxicity, are widely predictive of cardiovascular adverse events, but whether these markers can predict postsurgical sepsis (SS) is unclear. METHODS: We retrospectively analyzed patients who underwent abdominal surgery from March 2013 to May 2023. We collected basic data, comorbidities, blood samples, echocardiology, electrocardiogram, and surgical data, as well as short-term outcome. The primary endpoints were postsurgical SS, in which logistic regression analyses can identify independent risk factors. The optimal cut-off value predictive postsurgical SS both P wave and PR interval were calculated in the receiver operating characteristic curve (ROC). RESULTS: A total of 1988 subjects were analyzed, and the incidence of postsurgical SS was 3.8%. The mean age at enrollment was 68.6 ± 7.1 years, and 53.2% of the participants were men. In the ROC analysis, the areas under the curve (AUC) for P wave and PR interval predictive postsurgical SS were 0.615 (95%CI, 0.548-0.683; p = 0.001) and 0.618 (95%CI, 0.554-0.682; p = 0.001), respectively. The P wave and PR interval predicted postoperative sepsis with optimal discrimination of 103 and 157 ms, with a sensitivity of 0.744 and 0.419, and a specificity of 0.427 and 0.760. P-wave less than 103 ms or PR interval less than 157 ms associated with a 2.06 or 2.33 fold increase occurred risk postsurgical SS. CONCLUSIONS: Shorter P-wave and PR intervals were both independently associated with postsurgical SS. These preoperative electrophysiological markers could have potential useful for early recognition of postoperative SS.

Evolution of proton pump inhibitor prescribing from 2017 to 2021 at 14 secondary and tertiary hospitals in China：a multicentre cross-sectional study.

OBJECTIVE: The objective of this study was to describe the trend in prescribing proton pump inhibitor (PPI) use and expenditure in both secondary and tertiary hospitals in China between 2017 and 2021. DESIGN: Multicentre cross-sectional survey. SETTING: China, 14 medical centres, January 2017 to December 2021. PARTICIPANTS: 537 284 participants who were treated with PPI in 14 medical centres of China, between January 2017 and December 2021 were included. MAIN OUTCOMES AND MEASURES: The rate of PPI prescriptions, the defined daily doses (DDDs), DDDs/1000 inhabitants per day (DDDs/TID) and expenditure were analysed and plotted to demonstrate changes in prescription PPI use and expenditure. RESULTS: For both outpatient and inpatient settings, the rate of PPI prescribing decreased from 2017 to 2021. In outpatient settings, decreased slightly from 3.4% to 2.8%, however, in inpatient settings, showed a progressive decrease from 26.7% to 14.0%. The overall rate of injectable PPI prescriptions for inpatients decreased significantly from 21.2% to 7.3% between 2017 and 2021. Decreased trends in usage of oral PPI were observed (from 280 750 DDDs to 255 121 DDDs) between 2017 and 2021. However, usage of injectable PPI showed a significantly decrease from 191 451 DDDs to 68 806 DDDs from 2017 to 2021. In terms of DDDs/TID of PPI for inpatients decreased dramatically from 52.3 to 30.2 for the past 5 years. Expenditure on oral PPI decreased slightly from ¥1.98 million (Chinese currency Renminbi 'yuan') to ¥1.23 million for the past 5 years, whereas expenditure on injectable PPI showed a marked decrease from ¥2.61 million to ¥0.94 million. There was no statistical difference in both PPI use and expenditure between secondary and tertiary hospitals during the study period. CONCLUSIONS: Decreased PPI use and expenditure were observed among secondary and tertiary hospitals over the past 5 years (2017-2021).

Cardiovascular toxicity induced by SSRIs: Analysis of spontaneous reports submitted to FAERS.

Depression diagnoses have surged recently, and selective serotonin reuptake inhibitors (SSRIs) are the go-to treatment. However, studies indicate that long-term use of SSRIs can increase cardiovascular risk without systematic evaluation of the drug class. To offer clinical guidance, we performed an evaluation of the association between the six most commonly prescribed SSRIs and cardiovascular adverse events. Using the FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q2 2022, we conducted a disproportionality analysis and determined the magnitude of significant signals using statistical shrinkage transformations. Our study revealed that arrhythmias, torsades de pointes/QT prolongation, cardiomyopathy, and hypertension were among the most prevalent adverse events linked to SSRIs. Our analysis also showed a significant association between SSRIs and the aforementioned adverse events, with higher incidence in middle-aged and elderly patients and women. We further observed a rising trend in the incidence of arrhythmias, torsades de pointes/QT prolongation, and hypertension, highlighting the need for heightened cardiac monitoring in patients on SSRIs.

Secular trend analysis of antibiotic utilisation in some hospitals in Southern Sichuan from 2010 to 2020.

In order to assess the effectiveness of the Special Antimicrobial Stewardship Campaign launched by Ministry of Health of China in 2011, this study focused on the effectiveness and trends in the clinical use of antimicrobial drugs in selected hospitals in Southern Sichuan, China. This study collected and analyzed antibiotic data from 9 hospitals in Southern Sichuanin 2010, 2015, and 2020, including the rate of antibiotic use, expense, the intensity of antibiotic use and antibiotic use during the type I incisions of perioperative period. After 10 years of continuous improvement, the utilization rate of antibiotics in outpatients of the 9 hospitals continued to decline and was controlled below 20% by 2020, while the utilization rate in inpatients also significantly decreased, most were controlled within 60%. The use intensity of antibiotics (DDD (defined daily doses) per 100 bed-days) decreased from an average of 79.95 in 2010 to 37.96 in 2020. The prophylactic use of antibiotics decreased significantly in type I incision. The proportion of use within 30 min-1 h before operation was significantly increased. After the special rectification and sustained development of the clinical application of antibiotics, the relevant indicators of antibiotics tend to be stable, indicating that this Administration of antimicrobial drugs is conducive to improving the level of rational clinical application of antibiotics.

A Novel Effector, FSE1, Regulates the Pathogenicity of Fusarium oxysporum f. sp. cubense Tropical Race 4 to Banana by Targeting the MYB Transcription Factor MaEFM-Like.

Phytopathogenic fungi secretes a range of effectors to manipulate plant defenses. Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is a soil-borne pathogen that causes destructive banana wilt disease. Understanding the molecular mechanisms behind Foc TR4 effectors and their regulation of pathogenicity is helpful for developing disease control strategies. In the present study, we identified a novel effector, Fusarium special effector 1 (FSE1), in Foc TR4. We constructed FSE1 knock-out and overexpression mutants and investigated the functions of this effector. In vitro assays revealed that FSE1 was not required for vegetative growth and conidiation of Foc TR4. However, inoculation analysis of banana plantlets demonstrated that knock-out of FSE1 increased the disease index, while overexpression of FSE1 decreased it. Microscope analysis suggested that FSE1 was distributed in the cytoplasm and nuclei of plant cells. Furthermore, we identified an MYB transcription factor, MaEFM-like, as the target of FSE1, and the two proteins physically interacted in the nuclei of plant cells. In addition, Transient expression of MaEFM-like induced cell death in tobacco leaves. Our findings suggest that FSE1 is involved in the pathogenicity of Foc TR4 by targeting MaEFM-like.

Colletotrichum gloeosporioides Cg2LysM contributed to virulence toward rubber tree through affecting invasive structure and inhibiting chitin-triggered plant immunity.

Fungal chitin, as a typical microorganism-associated molecular pattern (PAMP), was recognized by plant LysM-containing protein to induce immunity called pattern-triggered immunity (PTI). To successfully infect host plant, fungal pathogens secreted LysM-containing effectors to inhibit chitin-induced plant immunity. Filamentous fungus Colletotrichum gloeosporioides caused rubber tree anthracnose which resulted in serious loss of natural rubber production worldwide. However, little is known about the pathogenesis mediated by LysM effector of C. gloeosporioide. In this study, we identified a two LysM-containing effector in C. gloeosporioide and named as Cg2LysM. Cg2LysM was involved not only in conidiation, appressorium formation, invasion growth and the virulence to rubber tree, but also in melanin synthesis of C. gloeosporioides. Moreover, Cg2LysM showed chitin-binding activity and suppression of chitin-triggered immunity of rubber tree such as ROS production and the expression of defense relative genes HbPR1, HbPR5, HbNPR1 and HbPAD4. This work suggested that Cg2LysM effector facilitate infection of C. gloeosporioides to rubber tree through affecting invasive structure and inhibiting chitin-triggered plant immunity.

Sharply and simultaneously increasing pollutant accumulations in cells of organisms induced by rare earth elements in the environment of Nanjing.

Exploring the factors that simultaneously increase the accumulation of various pollutants in cells of organisms to restrict the toxic effects of pollutants on organisms has become a focus of research aimed at protecting ecosystems. Here, we found that the accumulation of organic [e.g., benzo(a)pyrene (BaP)], inorganic [e.g., cadmium (Cd)] and emerging [e.g., rare earth elements (REEs)] pollutants in leaf cells of different plants grown in Nanjing was 567-1022%, 547-922% and 972-1392% of those grown in Haikou, respectively, when the concentration of REEs in rainwater of Nanjing and Haikou was 4.31 × 10-3 µg/L and 3.04 × 10-6 µg/L. Unprecedentedly, endocytosis in leaf cells of different plants grown in Nanjing was activated by REEs, and then extracellular BaP, Cd and REEs (e.g. terbium) were transported into these leaf cells together via endocytic vesicles. Particularly, the co-accumulation of those pollutants in these leaf cells was sharply increased, thus magnifying their toxic effects on these plants. Furthermore, the co-accumulation of those pollutants in human cells was also significantly increased by REEs, in a similar way to these leaf cells. Therefore, REEs in environments are key factors that greatly increase the co-accumulation of various pollutants in cells of organisms. These results provide new insights into how pollutants are accumulated in cells of organisms in ecosystems, informing a reference for making policy to ensure the safety of ecosystems.

Metabolomic and transcriptomic analyses provide insights into metabolic networks during cashew fruit development and ripening.

Cashew nut is a popular food around the world. The high-resolution profiles and dynamics of metabolomes in cashew fruits are poorly understood till now. In this study, we analyzed the temporal metabolome of cashew nut via a non-targeted method based on UHPLC-Q-Exactive-MS, and analyzed that of cashew apple via a widely targeted method based on UHPLC-QTRAP-MS/MS (MRM). Furthermore, we performed integrative analyses of temporal metabolome and transcriptome data, characterized the accumulation of specific metabolites, and identified the transcriptional changes during cashew fruit development. Specifically, we found that phosphatidylinositol species were the predominant fractions in the unsaturated glycerophospholipids, and we identified a transcription factor that was the potential regulator of phosphatidylinositol biosynthesis. Analysis of cashew apple revealed metabolic genes and transcription factors involved in sugar biosynthesis. Taken together, our results provide insights into metabolic networks during cashew fruit development and generate a valuable resource for further cashew breeding studies.

Pacemaker activity and ion channels in the sinoatrial node cells: MicroRNAs and arrhythmia.

The primary pacemaking activity of the heart is determined by a spontaneous action potential (AP) within sinoatrial node (SAN) cells. This unique AP generation relies on two mechanisms: membrane clocks and calcium clocks. Nonhomologous arrhythmias are caused by several functional and structural changes in the myocardium. MicroRNAs (miRNAs) are essential regulators of gene expression in cardiomyocytes. These miRNAs play a vital role in regulating the stability of cardiac conduction and in the remodeling process that leads to arrhythmias. Although it remains unclear how miRNAs regulate the expression and function of ion channels in the heart, these regulatory mechanisms may support the development of emerging therapies. This study discusses the spread and generation of AP in the SAN as well as the regulation of miRNAs and individual ion channels. Arrhythmogenicity studies on ion channels will provide a research basis for miRNA modulation as a new therapeutic target.

Comprehensive analysis of chemokines family and related regulatory ceRNA network in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the world's commonest malignancies with a high fatality rate. Chemokines not only regulate immune response but also participate in tumor development and metastasis and yet the mechanism of chemokines in LUAD remains unclear. In this study, transcriptional expression profiles, mutation data, and copy number variation data were downloaded from The Cancer Genome Atlas (TCGA). Risk gene protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA). Gene Expression Omnibus (GEO) data was used to validate the prognostic model. We summarized the genetic mutation variation landscape of chemokines. The risk prognosis model was developed based on differentially expressed chemokines, and patients in the high-risk score (RS) group had lower survival rates. Gene Set Enrichment Analysis (GSEA) revealed that high-RS patients were associated with metabolic transformation pathways, while low-RS patients were associated with immune-related pathways. Compared with the high-RS group, the low-RS group had higher immune/stromal/estimate scores calculated by the ESTIMATE package. The proportion of immune cells obtained using the CIBERSORT package was significantly different between the two groups. Most of the immune checkpoints were highly expressed in low-RS samples. Finally, we discovered that the lncRNA MIR17HG/AC009299.3/miR-21-5p/CCL20 regulatory network might be crucial in the pathogenesis of LUAD. In conclusion, we developed a risk signature and chemokine-related competing endogenous RNA (ceRNA) network.

Efficacy of administrative intervention for neurosurgical patients with off-label use of alprostadil lipid microsphere.

As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE1) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE1 is very common. This study aimed to investigate the use of Lipo-PGE1 and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE1 in neurosurgical patients in a Chinese tertiary hospital. Administrative interventions were implemented from January to December 2018 by reducing the procurement volume of Lipo-PGE1, judging the rationality of medical records, and establishing reward and punishment mechanisms. Administrative interventions significantly decreased prescription rate (49.98% vs 22.49%), utilization (22,311 DDDs vs 8334 DDDs), drug use density (43.52 DDDs/TID vs 15.84 DDDs/TID), total expenditure (3.58 million RMB vs 1.30 million RMB), and average expenditure (2025.04 RMB vs 1466.49 RMB) of Lipo-PGE1. To our delight, these intervention effects were maintained or even better in the 1-year post-intervention period. Moreover, in the intervention and post-intervention phases, the Lipo-PGE1 use for no indications as well as inappropriate drug dose, frequency, menstruum type, combination, and contraindication were markedly reduced. Besides, the mean costs (P < 0.001), and mean duration (P < 0.001) of Lipo-PGE1 were also obviously decreased. The administrative intervention obviously reduced the off-label use of Lipo-PGE1. However, there still remains a number of inappropriate uses of Lipo-PGE1. To further improve the rational use of Lipo-PGE1, combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.

Effects of Cabya (Piper retrofractum Vahl.) Fruit Developmental Stage on VOCs.

The differences in VOCs can affect the flavor and medicinal value of cabya, and the flavor changes that occur in stages as the fruit develops are currently unknown. In order to investigate the influence of the developmental stage on the aroma composition of cabya essential oil, VOCs at each of the four developmental stages were analyzed by steam distillation (SD) extraction combined with GC-MS detection. The similarities and differences in fruit composition among the developmental stages were evaluated using hierarchical cluster analysis (HCA) and principal component analysis (PCA). A total of 60 VOCs, mainly alcohols, alkenes and alkanes, were identified across all of the developmental stages. The most acidic substances were detected in phase A and have a high medicinal value. There was no significant difference between the B and C phases, and the alcohols in those phases mainly promoted terpenoid synthesis in the D phase. Constituents during the D phase were mainly alkenes, at 57.14%, which contributed significantly to the aroma of the essential oil. PCA and HCA both were able to effectively differentiate the cabya fruit developmental stages based on the SD-GC-MS data. In summary, this study investigated the flavor variation characteristics and the diversity of VOCs in cabya fruits at different developmental stages, and its findings can provide a reference for developing essential oil products for different uses and determining appropriate stages for harvesting cabya resources.

Actin-bundling protein fimbrin regulates pathogenicity via organizing F-actin dynamics during appressorium development in Colletotrichum gloeosporioides.

Anthracnose caused by Colletotrichum gloeosporioides leads to serious economic loss to rubber tree yield and other tropical crops. The appressorium, a specialized dome-shaped infection structure, plays a crucial role in the pathogenesis of C. gloeosporioides. However, the mechanism of how actin cytoskeleton dynamics regulate appressorium formation and penetration remains poorly defined in C. gloeosporioides. In this study, an actin cross-linking protein fimbrin homologue (CgFim1) was identified in C. gloeosporioides, and the knockout of CgFim1 led to impairment in vegetative growth, conidiation, and pathogenicity. We then investigated the roles of CgFim1 in the dynamic organization of the actin cytoskeleton. We observed that actin patches and cables localized at the apical and subapical regions of the hyphal tip, and showed a disc-to-ring dynamic around the pore during appressorium development. CgFim1 showed a similar distribution pattern to the actin cytoskeleton. Moreover, knockout of CgFim1 affected the polarity of the actin cytoskeleton in the hyphal tip and disrupted the actin dynamics and ring structure formation in the appressorium, which prevented polar growth and appressorium development. The CgFim1 mutant also interfered with the septin structure formation. This caused defects in pore wall overlay formation, pore contraction, and the extension of the penetration peg. These results reveal the mechanism by which CgFim1 regulates the growth and pathogenicity of C. gloeosporioides by organizing the actin cytoskeleton.

NADPH Oxidases Play a Role in Pathogenicity via the Regulation of F-Actin Organization in Colletotrichum gloeosporioides.

Multiunit-flavoenzyme NADPH oxidases (NOXs) play multiple roles in living cells via regulating signaling pathways. In several phytopathogenic fungi, NOXs are required for the polarized growth of hyphal tips and pathogenicity to host plants, but the possible mechanisms are still elusive. In our previous study, CgNOXA, CgNOXB, and CgNOXR were identified as components of the NOX complex in Colletotrichum gloeosporioides. The growth and the inoculation assays revealed that CgNOXA/B and CgNOXR regulate vegetative growth and are required for the full pathogenicity of C. gloeosporioides to Hevea leaves. We further demonstrated that the vital roles of CgNOXB and CgNOXR in appressorium formation and the development of invasion hyphae account for their functions in pathogenicity. Moreover, CgNOXB and CgNOXR regulate the production and distribution of ROS in hyphal tips and appressoria, control the specialized remodeling of F-actin in hyphal tips and appressoria, and are involved in fungal cell wall biosynthesis. Taken together, our findings highlight the role of NOXs in fungal pathogenicity through the organization of the actin cytoskeleton.

The Effector Protein CgNLP1 of Colletotrichum gloeosporioides Affects Invasion and Disrupts Nuclear Localization of Necrosis-Induced Transcription Factor HbMYB8-Like to Suppress Plant Defense Signaling.

Fungi secrete numerous effectors to modulate host defense systems. Understanding the molecular mechanisms by which fungal effectors regulate plant defense is of great importance for the development of novel strategies for disease control. In this study, we identified necrosis- and ethylene-inducing protein 1 (Nep1)-like protein (NLP) effector gene, CgNLP1, which contributed to conidial germination, appressorium formation, invasive growth, and virulence of Colletotrichum gloeosporioides to the rubber tree. Transient expression of CgNLP1 in the leaves of Nicotiana benthamiana induced ethylene production in plants. Ectopic expression of CgNLP1 in Arabidopsis significantly enhanced the resistance to Botrytis cinerea and Alternaria brassicicola. An R2R3 type transcription factor HbMYB8-like of rubber tree was identified as the target of CgNLP1.HbMYB8-like, localized on the nucleus, and induced cell death in N. benthamiana. CgNLP1 disrupted nuclear accumulation of HbMYB8-like and suppressed HbMYB8-like induced cell death, which is mediated by the salicylic acid (SA) signal pathway. This study suggested a new strategy whereby C. gloeosporioides exploited the CgNLP1 effector to affect invasion and suppress a host defense regulator HbMYB8-like to facilitate infection.

Impact of proton pump inhibitor management committee's multifaceted interventions on acid suppressant prescribing patterns in outpatient and emergency departments.

BACKGROUND: A nationwide campaign for rational proton pump inhibitor (PPI) use launched in 2015 had a positive impact for hospitalized patients PPI use. But there were few studies focusing on the rational use of PPIs in outpatients. In 2018, the PPI management committee conducted a year-long intervention on the appropriate use of PPIs in outpatient and emergency departments, including clinical pharmacist interventions and stewardship interventions. The purpose of this study was to examine the impact of the PPI management committee's multifaceted interventions by comparing the real-world acid suppressant prescribing patterns for outpatients before (2017) and after intervention (2019) at a Chinese tertiary teaching hospital. METHODS: Prescriptions containing any acid suppressant in outpatient and emergency departments in baseline (2017) and postintervention (2019) periods were extracted from the hospital information system and the prescription automatic screening system. Acid suppressant prescribing patterns were evaluated based on primary diagnoses and patient demographics. The prescribed acid suppressants stratified using age groups (< 7, 7-17, 18-45, 46-65, 66-85 and > 85 years) were also examined. RESULT: The utilization rate of acid suppressant in 2017 and 2019 was 2.5% (41,165/1,619,366) and 2.2% (49,550/2,236,471), respectively (P < 0.0001). 60,135 acid suppressant prescriptions were obtained in 2017 and 73,275 in 2019. The rate of acid suppressant prescriptions for the approved indications significantly increased from 62.6% (2017) to 65.4% (2019) (P < 0.0001). Prescriptions diagnosed as abnormal symptoms, signs and clinical manifestations, decreased in 2019 (13.0% vs. 16.5%, P < 0.0001). The most frequently prescribed PPIs differed between 2017 and 2019 (rabeprazole 2017 vs. esomeprazole 2019). Omeprazole was the most common PPI and cimetidine was the most common H2RA prescribed to patients aged < 18 years in 2017 and 2019. A total of CNY11.83 million was spent on acid suppressants in 2019, accounting for about 48.7% of total medication cost, increased by 11.3% from 2017 (37.4%). CONCLUSION: The proportion of acid suppressant prescriptions for approved indications was enhanced after the PPI management committee's multifaceted interventions, but there were still some problems in the selection of acid suppressants.