Anti-thermal quenching phosphors based on the new phosphate host Ca3.6In3.6(PO4)6.

To enhance the working quality of WLEDs, considerable efforts have been made to upgrade the thermal quenching resistance of existing phosphors or design new anti-thermal quenching (ATQ) phosphors. Developing a new phosphate matrix material with special structural features has great importance for the fabrication of ATQ phosphors. By phase relationship and composition analysis, we have prepared a novel compound Ca3.6In3.6(PO4)6 (CIP). Coupling ab initio and Rietveld refinement techniques, the novel structure of CIP with partly vacant cationic positions was solved. Taking this unique compound as the host and using the inequivalent substitution of Dy3+ for Ca2+, a series of C1-xIP:Dy3+ rice-white emitting phosphors were successfully developed. When the temperature was raised to 423 K, the emission intensity of C1-xIP:xDy3+ (x = 0.01, 0.03, and 0.05) increased to 103.8%, 108.2%, and 104.5% of the original intensity at 298 K, respectively. Except for the strong bonding network and inherent cationic vacancy in the lattice, the ATQ property of the C1-xIP:Dy3+ phosphors is mainly attributed to the generation of interstitial oxygen from the substitution of unequal ions, which releases electrons with the thermal stimulus, causing anomalous emission. Finally, we have explored the quantum efficiency of C1-xIP:0.03Dy3+ phosphor and the working performance of PC-WLED prepared with C1-xIP:0.03Dy3+ phosphor and 365 nm chip. The research work sheds light on the relationship between lattice defects and thermal stability, and meanwhile offers a new strategy for the development of ATQ phosphors.

Two New C21 Steroidal Glycosides from Selaginella Braunii Baker.

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.

Decoding the Mechanism of Shixiao Powder in Treating Coronary Heart Disease Based on Network Pharmacology and Molecular Docking.

Shixiao powder comes from the Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and consists of two herbs, Puhuang (PH) and Wulingzhi (WLZ). PH-WLZ is a commonly used drug pair for the treatment of coronary heart disease (CHD), and its clinical effect is remarkable. However, our understanding of the mechanism of treatment of CHD is still unclear. In this study, the method of network pharmacology was used to explore the mechanism of PH-WLZ in the treatment of CHD. A total of 56 active ingredients were identified from PH-WLZ, of which 93 targets of 41 active ingredients overlapped with those of CHD. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with CHD and those associated with the mechanism of PH-WLZ in the treatment of CHD. By constructing the protein-protein interaction (PPI) network of common targets, 10 hub genes were identified. Based on the number of hub genes contained in the enrichment analysis, we obtained the key pathways of PH-WLZ in the treatment of CHD. The key KEGG pathway in the treatment of CHD by PH-WLZ is mainly enriched in atherosclerosis, inflammation, immunity, oxidative stress, and infection-related pathways. Moreover, the results of molecular docking showed that the active ingredients of PH-WLZ had a good affinity with the hub genes. The results indicate that the mechanism of PH-WLZ in the treatment of CHD may be related to regulation of lipid metabolism, regulation of immune and inflammatory responses, regulation of downstream genes of fluid shear stress, antiaging and oxidative stress, and virus inhibition.

Case Report: Chemotherapy and Radiotherapy Combined With DC-CIK for Pulmonary and Mediastinal Metastases From Nasopharyngeal Carcinoma.

INTRODUCTION: The optimal treatment for pulmonary and mediastinal metastasis of nasopharyngeal carcinoma (NPC) is still controversial, and the therapeutic effect is poor recently. In one case, we demonstrated a long-term survival after postoperative chemoradiotherapy combined with dendritic cell and cytokine-induced killer (DC-CIK) immunotherapy for pulmonary and mediastinal metastases from NPC. BASELINE CHARACTERISTICS: A 53-year-old woman was admitted to our hospital in June 2008. Pathological biopsy revealed a poorly differentiated squamous cell carcinoma located in the nasopharynx with the invasion of internal pterygoid muscles, the sphenoid bone, and unilateral neck lymph node metastasis. No distant metastases were observed. The stage of NPC was T3N1M0 III (AJCC8). The patient received concurrent chemoradiotherapy for primary lesion and neck lymph nodes and achieved complete remission (CR) of the disease after 3 months. Follow-up at 3-month intervals was carried out. Pulmonary and mediastinal lymph node metastases were found in July 2009. The patient then underwent right upper lobectomy and mediastinal lymph node dissection and five cycles of gemcitabine and cisplatin (GP) regimen chemotherapy, following radiotherapy and DC-CIK immunotherapy. RESULTS: After a follow-up time of 13 years, no tumor recurrence or metastasis and severe adverse reactions were found. CONCLUSION: Postoperative chemotherapy and radiotherapy in combination with DC-CIK immunotherapy may produce a synergistic therapeutic effect on patients with mediastinal lymph node metastasis from NPC.

Cyclophilin BcCyp2 Regulates Infection-Related Development to Facilitate Virulence of the Gray Mold Fungus Botrytis cinerea.

Cyclophilin (Cyp) and Ca2+/calcineurin proteins are cellular components related to fungal morphogenesis and virulence; however, their roles in mediating the pathogenesis of Botrytis cinerea, the causative agent of gray mold on over 1000 plant species, remain largely unexplored. Here, we show that disruption of cyclophilin gene BcCYP2 did not impair the pathogen mycelial growth, osmotic and oxidative stress adaptation as well as cell wall integrity, but delayed conidial germination and germling development, altered conidial and sclerotial morphology, reduced infection cushion (IC) formation, sclerotial production and virulence. Exogenous cyclic adenosine monophosphate (cAMP) rescued the deficiency of IC formation of the ∆Bccyp2 mutants, and exogenous cyclosporine A (CsA), an inhibitor targeting cyclophilins, altered hyphal morphology and prevented host-cell penetration in the BcCYP2 harboring strains. Moreover, calcineurin-dependent (CND) genes are differentially expressed in strains losing BcCYP2 in the presence of CsA, suggesting that BcCyp2 functions in the upstream of cAMP- and Ca2+/calcineurin-dependent signaling pathways. Interestingly, during IC formation, expression of BcCYP2 is downregulated in a mutant losing BcJAR1, a gene encoding histone 3 lysine 4 (H3K4) demethylase that regulates fungal development and pathogenesis, in B. cinerea, implying that BcCyp2 functions under the control of BcJar1. Collectively, our findings provide new insights into cyclophilins mediating the pathogenesis of B. cinerea and potential targets for drug intervention for fungal diseases.

The outcome and burden of Chinese patients with neurodegenerative diseases: A 10-year clinical feature study.

BACKGROUND: As the Chinese population continues to age, the incidence of neurodegenerative diseases (NDDs) has increased dramatically, which results in heavy medical and economic burden for families and society. OBJECTIVE: The objective of this study was to evaluate NDDs in a southern Chinese hospital over a 10-year period and examine trends in demographics, outcome, length of stay (LOS) and cost. METHODS: Retrospective medical records of patients from January 2010 to December 2019 were collected, including 7231 patients with NDDs (as case group) and 9663 patients without any NDDs (as control group). The information of social demographic data, admission source, reasons for admission, outcomes, LOS, and cost were extracted and analysed. RESULT: The average hospitalisation age of the patients with NDDs is over 65 years (peak age 70-89 years). Compared with the control group, the case group had a longer LOS and a higher cost and the numbers of patients with NDDs increased yearly from 2010 to 2019. The LOS shortened while the cost increased. Clinical features affected LOS and cost. Patients suffering from infection, abnormal blood pressure and the imbalance of water-electrolyte homoeostasis as main reasons for admission were decreased; however, heart disease, cerebrovascular accident and mental diseases were significantly increased, the overall change trend of fracture/trauma remained stable. The rate of discharge to home care and mortality declined; discharge to other medical or community facilities increased over 10 years. CONCLUSION: The majority of NDDs patients tended to be older. During the last 10 years from 2010 to 2019, the numbers of NDDs patients increased yearly, the trend of LOS became shortening and the cost gradually increasing. The main reasons of admission and outcomes of hospital showed different trends.

Smad2/4 Signaling Pathway Is Critical for Epidermal Langerhans Cell Repopulation Under Inflammatory Condition but Not Required for Their Homeostasis at Steady State.

Epidermal Langerhans cells (LCs) are skin-resident dendritic cells that are essential for the induction of skin immunity and tolerance. Transforming growth factor-ß 1 (TGFß1) is a crucial factor for LC maintenance and function. However, the underlying TGFß1 signaling pathways remain unclear. Our previous research has shown that the TGFß1/Smad3 signaling pathway does not impact LC homeostasis and maturation. In this study, we generated mice with conditional deletions of either individual Smad2, Smad4, or both Smad2 and Smad4 in the LC lineage or myeloid lineage, to further explore the impact of TGFß1/Smad signaling pathways on LCs. We found that interruption of Smad2 or Smad4 individually or simultaneously in the LC lineage did not significantly impact the maintenance, maturation, antigen uptake, and migration of LCs in vivo or in vitro during steady state. However, the interruption of both Smad2 and Smad4 pathways in the myeloid lineage led to a dramatic inhibition of bone marrow-derived LCs in the inflammatory state. Overall, our data suggest that canonical TGFß1/Smad2/4 signaling pathways are dispensable for epidermal LC homeostasis and maturation at steady state, but are critical for the long-term LC repopulation directly originating from the bone marrow in the inflammatory state.

Transcriptome analysis and functional validation reveal a novel gene, BcCGF1, that enhances fungal virulence by promoting infection-related development and host penetration.

Simultaneous transcriptome analyses of both host plants and pathogens, and functional validation of the identified differentially expressed genes (DEGs) allow us to better understand the mechanisms underlying their interactions. Here, we analyse the mixed transcriptome derived from Botrytis cinerea (the causal agent of grey mould) infected tomato leaves at 24 hr after inoculation, a critical time point at which the pathogen has penetrated and developed in the leaf epidermis, whereas necrotic symptoms have not yet appeared. Our analyses identified a complex network of genes involved in the tomato-B. cinerea interaction. The expression of fungal transcripts encoding candidate effectors, enzymes for secondary metabolite biosynthesis, hormone and reactive oxygen species (ROS) production, and autophagy-related proteins was up-regulated, suggesting that these genes may be involved in the initial infection processes. Specifically, tomato genes involved in phytoalexin production, stress responses, ATP-binding cassette transporters, pathogenesis-related proteins, and WRKY DNA-binding transcription factors were up-regulated. We functionally investigated several B. cinerea DEGs via gene replacement and pathogenicity assays, and demonstrated that BcCGF1 was a novel virulence-associated factor that mediates fungal development and virulence via regulation of conidial germination, conidiation, infection structure formation, host penetration, and stress adaptation. The fungal infection-related development was controlled by BcCGF-mediated ROS production and exogenous cAMP restored the mutant infection-related development. Our findings provide new insights into the elucidation of the simultaneous tactics of pathogen attack and host defence. Our systematic elucidation of BcCGF1 in mediating fungal pathogenesis may open up new targets for fungal disease control.

The Non-Concentration-Quenching Phosphor Ca3Eu2B4O12 for WLED Application.

Commercial white LED devices usually suffer from a high color temperature and poor color rendering. Developing a new, efficient, and stable red phosphor is the key to solving this problem. In this work, a series of pure Ca3Y2-xB4O12:xEu3+ (0 < x ≤ 2) samples, including the new and fully transitional borate phosphor Ca3Eu2B4O12 (CEBO), have been successfully prepared by solid-state reaction synthesis. CEBO is isostructural with Ca3Y2B4O12 (CYBO), belonging to the orthorhombic system with space group Pnma (No. 62). Under optimal 393 nm excitation, this borate exhibits a strong red emission, peaking at 615 nm, with high color purity. Interestingly, the luminescence of CEBO is relatively higher than that of CYBO:Eu3+ phosphors. The quantum yield of this non-concentration-quenching phosphor reaches 95.6%. Furthermore, a warm pc-WLED device has been fabricated by mixing as-prepared CEBO powders and commercial BaMgAl10O17:Eu2+ and (Sr, Ba)2SiO4:Eu2+ phosphors, which exhibits a high color rendering index (Ra = 83.7) along with a color temperature of around 3883 K. The present work indicates that this new borate, with outstanding quantum efficiency and favorable thermal stability, can be used as a red phosphor for application in WLEDs.

Efficient and stable Sr3Eu2B4O12 red phosphor benefiting from low symmetry and distorted local environment.

The development of suitable red phosphors to obtain improved white color stands a good chance to serve in the new generation of white light-emitting diodes. Owing to multi-elements via doping and oxidation of reduced valence state of lanthanide or transition metal ions, most of the reported phosphors usually suffer from complex synthetic processes and unstable color of the lighting industry cycle. In this work, we present a new red emitting and stable Sr3Eu2B4O12 phosphor with regard to its special structure. It crystallizes as an orthorhombic cell, with Sr and Eu atoms co-occupying three different lattice sites in the space group of Pnma (no. 62). It is proposed that the long bond distance between activators minimizes the content quenching, while the high disorder of location restricts the thermal quenching. This phosphor emits bright red light with good color purity under UV excitation, with the luminescence intensity and quantum yield tunable via the fabrication temperature. Through a preliminary optimization of the synthesis process, the Sr3Eu2B4O12 phosphor prepared at 1250 °C has high quantum yields of about 94.7% and excellent thermal stability of 85.6% intensity retention at 150 °C relative to the initial value at room temperature. The calculated Judd-Ofelt intensity parameters (Ω2, Ω4) further clarified that the Eu3+ site in Sr3Eu2B4O12 had lower symmetry without an inversion center, and more distorted local environment and structural rigidity of the host, predicting excellent thermal stability. Finally, a warm pc-WLED device has been produced by mixing as-prepared Sr3Eu2B4O12 powders and commercial BaMgAl10O17:Eu2+ and (Sr, Ba)2SiO4:Eu2+ phosphors, which exhibits a high color rendering index (Ra = 83.4) along with a color temperature at around 4102 K. The present work indicates that the Sr3Eu2B4O12 phosphor is an efficient red component with excellent thermal stability for white-light production of near-UV-excited w-LEDs.

The H3K4 demethylase Jar1 orchestrates ROS production and expression of pathogenesis-related genes to facilitate Botrytis cinerea virulence.

Histone 3 Lysine 4 (H3K4) demethylation is ubiquitous in organisms, however the roles of H3K4 demethylase JARID1(Jar1)/KDM5 in fungal development and pathogenesis remain largely unexplored. Here, we demonstrate that Jar1/KDM5 in Botrytis cinerea, the grey mould fungus, plays a crucial role in these processes. The BcJAR1 gene was deleted and its roles in fungal development and pathogenesis were investigated using approaches including genetics, molecular/cell biology, pathogenicity and transcriptomic profiling. BcJar1 regulates H3K4me3 and both H3K4me2 and H3K4me3 methylation levels during vegetative and pathogenic development, respectively. Loss of BcJAR1 impairs conidiation, appressorium formation and stress adaptation; abolishes infection cushion (IC) formation and virulence, but promotes sclerotium production in the ΔBcjar1 mutants. BcJar1 controls reactive oxygen species (ROS) production and proper assembly of Sep4, a core septin protein and virulence determinant, to initiate infection structure (IFS) formation and host penetration. Exogenous cAMP partially restored the mutant appressorium, but not IC, formation. BcJar1 orchestrates global expression of genes for ROS production, stress response, carbohydrate transmembrane transport, secondary metabolites, etc., which may be required for conidiation, IFS formation, host penetration and virulence of the pathogen. Our work systematically elucidates BcJar1 functions and provides novel insights into Jar1/KDM5-mediated H3K4 demethylation in regulating fungal development and pathogenesis.

A high-density genetic map developed by specific-locus amplified fragment (SLAF) sequencing and identification of a locus controlling anthocyanin pigmentation in stalk of Zicaitai (Brassica rapa L. ssp. chinensis var. purpurea).

BACKGROUND: Caixin and Zicaitai (Brassica rapa) belong to Southern and Central China respectively. Zicaitai contains high amount of anthocyanin in leaf and stalk resulting to the purple color. Stalk is the major edible part and stalk color is an economically important trait for the two vegetables. The aim of this study is to construct a high density genetic map using the specific length amplified fragment sequencing (SLAF-seq) technique to explore genetic basis for anthocyanin pigmentation traits via quantitative trait loci (QTL) mapping. RESULTS: We constructed a high generation linkage map with a mapping panel of F2 populations derived from 150 individuals of parental lines "Xianghongtai 01" and "Yinong 50D" with purple and green stalk respectively. The map was constructed containing 4253 loci, representing 10,940 single nucleotide polymorphism (SNP) markers spanning 1030.04 centiMorgans (cM) over 10 linkage groups (LGs), with an average distance between markers of 0.27 cM. Quantitative trait loci (QTL) analysis revealed that a major locus on chromosome 7 and 4 minor QTLs explaining 2.69-61.21% of phenotypic variation (PVE) were strongly responsible for variation in stalk color trait. Bioinformatics analysis of the major locus identified 62 protein-coding genes. Among the major locus, there were no biosynthetic genes related to anthocyanin. However, there were several transcription factors like helix-loop-helix (bHLH) bHLH, MYB in the locus. Seven predicted candidate genes were selected for the transcription level analysis. Only bHLH49 transcription factor, was significantly higher expressed in both stalks and young leaves of Xianghongtai01 than Yinong50D. An insertion and deletion (InDel) marker developed from deletion/insertion in the promoter region of bHLH49 showed significant correlation with the stalk color trait in the F2 population. CONCLUSION: Using the constructed high-qualified linkage map, this study successfully identified QTLs for stalk color trait. The identified valuable markers and candidate genes for anthocyanin accumulation in stalk will provide useful information for molecular regulation of anthocyanin biosynthesis. Overall our findings will lay a foundation for functional gene cloning, marker-assisted selection (MAS) and molecular breeding of important economic traits in B. rapa.

A novel Botrytis cinerea-specific gene BcHBF1 enhances virulence of the grey mould fungus via promoting host penetration and invasive hyphal development.

Botrytis cinerea is the causative agent of grey mould on over 1000 plant species and annually causes enormous economic losses worldwide. However, the fungal factors that mediate pathogenesis of the pathogen remain largely unknown. Here, we demonstrate that a novel B. cinerea-specific pathogenicity-associated factor BcHBF1 (hyphal branching-related factor 1), identified from virulence-attenuated mutant M8008 from a B. cinerea T-DNA insertion mutant library, plays an important role in hyphal branching, infection structure formation, sclerotial formation and full virulence of the pathogen. Deletion of BcHBF1 in B. cinerea did not impair radial growth of mycelia, conidiation, conidial germination, osmotic- and oxidative-stress adaptation, as well as cell wall integrity of the ∆Bchbf1 mutant strains. However, loss of BcHBF1 impaired the capability of hyphal branching, appressorium and infection cushion formation, appressorium host penetration and virulence of the pathogen. Moreover, disruption of BcHBF1 altered conidial morphology and dramatically impaired sclerotial formation of the mutant strains. Complementation of BcHBF1 completely rescued all the phenotypic defects of the ∆Bchbf1 mutants. During young hyphal branching, host penetration and early invasive growth of the pathogen, BcHBF1 expression was up-regulated, suggesting that BcHBF1 is required for these processes. Our findings provide novel insights into the fungal factor mediating pathogenesis of the grey mould fungus via regulation of its infection structure formation, host penetration and invasive hyphal branching and growth.

NF-κB inhibitor on Toll-like receptor 4 signal-induced expression of angiotensinogen and AT1a receptor in neonatal rat left ventricular myocytes.

Effects of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway on expression of angiotensinogen and AT1a receptor were investigated, to explore the role of TLR4/NF-κB signaling pathway in cardiovascular disease. Neonatal rat left ventricular myocytes (NRVMs) were cultured and cardiomyocytes were identified by immunocytochemical staining of sarcomeric α-actin. NRVMs were treated with lipopolysaccharide (LPS) at a dose of 10, 100 and 1,000 ng/ml, and RT-PCR was performed 24 h later to detect the expression of TLR4, angiotensinogen (ATG) and AT1a at mRNA level. NRVMs were cultured and pretreated with caffeic acid phenethylester (CAPE) for 30 min. Then NRVMs were stimulated with LPS (1,000 ng/ml) for 24 h. Nuclear translocation of NF-κB p65 was detected by immunocytochemistry. Expression of TLR4, angiotensinogen and AT1a receptor after CAPE stimulation was detected by RT-PCR. TLR4 mRNA was highly expressed in in vitro cultured NRVMs, and the expression level was significantly increased by LPS (10-1,000 ng/ml) stimulation in a dose-dependent manner (P<0.05). LPS stimulation also significantly increased the expression levels of angiotensinogen and AT1a receptor in a dose-dependent manner (P<0.05). NF-κB was activated and nuclear translocation of NF-κB p65 occurred after stimulation with LPS (1,000 ng/ml) for 24 h, while CAPE (20 µg/ml) inhibited the nuclear translocation of NF-κB p65 and inhibited LPS-induced expression of angiotensinogen and AT1a receptor. With LPS stimulation, TLR4 signaling positively regulates the expression of TLR4 and upregulates the expression of angiotensinogen and AT1a receptor in NRVMs. CAPE, an inhibitor of NF-κB, inhibited NF-κB p65 activation and inhibited the upregulation of TLR4, angiotensinogen and AT1a receptors induced by LPS. These results suggest that NF-κB plays a key regulatory role in the above-mentioned effects induced by LPS. Intervention with TLR4/NF-κB signaling may become a new target for prevention and treatment of cardiovascular diseases.

Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo.

BACKGROUND: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (ß5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. METHODS: In this study, we investigated the role of ß5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo. RESULTS: We showed that 6-OHDA upregulated ß5i expression in DA neurons in a concentration- and time-dependent manner. Inhibition and downregulation of ß5i induced the expression of glucose-regulated protein (Bip) and exacerbated 6-OHDA neurotoxicity in DA neurons. The inhibition of ß5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA. ß5i also activated transporter associated with antigen processing 1 (TAP1) and promoted MHC-I expression on DA neurons. CONCLUSION: Taken together, our data suggest that ß5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.

The key gluconeogenic gene PCK1 is crucial for virulence of Botrytis cinerea via initiating its conidial germination and host penetration.

The process of initiation of host invasion and survival of some foliar phytopathogenic fungi in the absence of external nutrients on host leaf surfaces remains obscure. Here, we demonstrate that gluconeogenesis plays an important role in the process and nutrient-starvation adaptation before the pathogen host invasion. Deletion of phosphoenolpyruvate carboxykinase gene BcPCK1 in gluconeogenesis in Botrytis cinerea, the causative agent of grey mould, resulted in the failure of the ΔBcpck1 mutant conidia to germinate on hard and hydrophobic surface and penetrate host cells in the absence of glucose, reduction in conidiation and slow conidium germination in a nutrient-rich medium. The wild-type and ΔBcpck1 conidia germinate similarly in the presence of glucose (higher concentration) as the sole carbon source. Conidial glucose-content should reach a threshold level to initiate germination and host penetration. Infection structure formation by the mutants displayed a glucose-dependent fashion, which corresponded to the mutant virulence reduction. Exogenous glucose or complementation of BcPCK1 completely rescued all the developmental and virulence defects of the mutants. Our findings demonstrate that BcPCK1 plays a crucial role in B. cinerea pathogenic growth and virulence, and provide new insights into gluconeogenesis mediating pathogenesis of plant fungal pathogens via initiation of conidial germination and host penetration.

The pre-rRNA processing factor Nop53 regulates fungal development and pathogenesis via mediating production of reactive oxygen species.

Botrytis cinerea is a necrotrophic plant fungal pathogen that annually causes enormous economic losses worldwide. The ribosome is an organelle for cellular protein biosynthesis. However, little is known about how the ribosome operates as a machine to mediate microbial pathogenesis. Here, we demonstrate that Nop53, a late-acting factor for 60S ribosomal subunit maturation, is crucial for the pathogen's development and virulence. BcNop53 is functionally equivalent to yeast nop53p. Complementation of BcNOP53 completely restored the growth defect of the yeast Δnop53 mutant. BcNop53 is located in nuclei and disruption of BcNOP53 also dramatically impaired pathogen growth. Deletion of BcNOP53 blocked infection structure formation and abolished virulence of the pathogen, possibly due to reduced production of reactive oxygen species. Moreover, loss of BcNOP53 impaired pathogen conidiation and stress adaptation, altered conidial and sclerotial morphology, retarded conidium and sclerotium germination as well as reduced the activities of cell-wall degradation-associated enzymes. Sclerotium production was, however, increased. Complementation with the wild-type BcNOP53 allele rescued defects found in the ΔBcnop53 mutant. Our work establishes a systematic elucidation of Nop53 in regulating microbial development and pathogenesis, provides novel insights into ribosomal processes that regulate fungal pathogenesis, and may open up new targets for addressing fungal diseases.

Outcome of a session of extracorporeal shock wave lithotripsy before endoscopic retrograde cholangiopancreatography for problematic and large common bile duct stones.

AIM: To compare the efficacy of a session of extracorporeal shock wave lithotripsy (ESWL) before endoscopic retrograde cholangiopancreatography (ERCP) vs ERCP only for problematic and large common bile duct (CBD) stones. METHODS: Adult patients with CBD stones for whom initial ERCP was unsuccessful because of the large size of CBD stones were identified. The patients were randomized into two groups, an "ESWL + ERCP group" and an "ERCP-only" group. For ESWL + ERCP cases, ESWL was performed prior to ERCP. Clearance of the CBD, complications related to the ESWL/ERCP procedure, frequency of mechanical lithotripsy use and duration of the ERCP procedure were evaluated in both groups. RESULTS: There was no significant difference in baseline characteristics between the two groups. A session of ESWL before ERCP compared with ERCP only resulted in similar outcomes in terms of successful stone removal within the first treatment session (74.2% vs 71.0%, P = 0.135), but a higher clearance rate within the second treatment session (84.4% vs 51.6%, P = 0.018) and total stone clearance (96.0% vs 86.0%, P = 0.029). Moreover, ESWL prior to ERCP not only reduced ERCP procedure time (43 ± 21 min vs 59 ± 28 min, P = 0.034) and the rate of mechanical lithotripsy use (20% vs 30%, P = 0.025), but also raised the clearance rate of extremely large stones (80.0% vs 40.0%, P = 0.016). Post-ERCP complications were similar for the two groups. CONCLUSION: Based on the higher rate of successful stone removal and minimal complications, ESWL prior to ERCP appears to be a safe and effective treatment for the endoscopic removal of problematic and large CBD stones.

Dynamic behaviors of a modified SIR model in epidemic diseases using nonlinear incidence and recovery rates.

The transmission of infectious diseases has been studied by mathematical methods since 1760s, among which SIR model shows its advantage in its epidemiological description of spread mechanisms. Here we established a modified SIR model with nonlinear incidence and recovery rates, to understand the influence by any government intervention and hospitalization condition variation in the spread of diseases. By analyzing the existence and stability of the equilibria, we found that the basic reproduction number [Formula: see text] is not a threshold parameter, and our model undergoes backward bifurcation when there is limited number of hospital beds. When the saturated coefficient a is set to zero, it is discovered that the model undergoes the Saddle-Node bifurcation, Hopf bifurcation, and Bogdanov-Takens bifurcation of codimension 2. The bifurcation diagram can further be drawn near the cusp type of the Bogdanov-Takens bifurcation of codimension 3 by numerical simulation. We also found a critical value of the hospital beds bc at [Formula: see text] and sufficiently small a, which suggests that the disease can be eliminated at the hospitals where the number of beds is larger than bc. The same dynamic behaviors exist even when a ≠ 0. Therefore, it can be concluded that a sufficient number of the beds is critical to control the epidemic.

The septin protein Sep4 facilitates host infection by plant fungal pathogens via mediating initiation of infection structure formation.

Many phytopathogenic fungi use infection structures (IFSs, i.e., appressoria and infection cushions) to penetrate host cuticles. However, the conserved mechanisms that mediate initiation of IFS formation in divergent pathogens upon sensing the presence of host plants remain obscure. Here, we demonstrate that a conserved septin gene SEP4 plays crucial roles in this process. Disruption of SEP4 in the plant grey mould fungus Botrytis cinerea completely blocked IFS formation and abolished the virulence of ΔBcsep4 mutants on unwounded hosts. During IFS formation, mutants lacking SEP4 could produce reactive oxygen species (ROS) normally. Inhibition of ROS production in strains harbouring the SEP4 gene resulted in disordered assembly of Sep4 and the subsequent failure to form infection cushions, suggesting that proper Sep4 assembly regulated by ROS is required for initiation of IFS formation and infection. Moreover, loss of SEP4 severely impaired mutant conidiation, melanin and chitin accumulation in hyphal tips and lesion expansion on wounded hosts, but significantly promoted germ tube elongation and sclerotium production. SEP4-mediated fungal pathogenic development, including IFS formation, was validated in the hemibiotroph Magnaporthe oryzae. Our findings indicate that Sep4 plays pleiotropic roles in B. cinerea development and specifically facilities host infection by mediating initiation of IFS formation in divergent plant fungal pathogens in response to ROS signaling.