The EDS1-PAD4-ADR1 node mediates Arabidopsis pattern-triggered immunity.

Plants deploy cell-surface and intracellular leucine rich-repeat domain (LRR) immune receptors to detect pathogens1. LRR receptor kinases and LRR receptor proteins at the plasma membrane recognize microorganism-derived molecules to elicit pattern-triggered immunity (PTI), whereas nucleotide-binding LRR proteins detect microbial effectors inside cells to confer effector-triggered immunity (ETI). Although PTI and ETI are initiated in different host cell compartments, they rely on the transcriptional activation of similar sets of genes2, suggesting pathway convergence upstream of nuclear events. Here we report that PTI triggered by the Arabidopsis LRR receptor protein RLP23 requires signalling-competent dimers of the lipase-like proteins EDS1 and PAD4, and of ADR1 family helper nucleotide-binding LRRs, which are all components of ETI. The cell-surface LRR receptor kinase SOBIR1 links RLP23 with EDS1, PAD4 and ADR1 proteins, suggesting the formation of supramolecular complexes containing PTI receptors and transducers at the inner side of the plasma membrane. We detected similar evolutionary patterns in LRR receptor protein and nucleotide-binding LRR genes across Arabidopsis accessions; overall higher levels of variation in LRR receptor proteins than in LRR receptor kinases are consistent with distinct roles of these two receptor families in plant immunity. We propose that the EDS1-PAD4-ADR1 node is a convergence point for defence signalling cascades, activated by both surface-resident and intracellular LRR receptors, in conferring pathogen immunity.

Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis.

INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.

Botrytis cinerea infection accelerates ripening and cell wall disassembly to promote disease in tomato fruit.

Postharvest fungal pathogens benefit from the increased host susceptibility that occurs during fruit ripening. In unripe fruit, pathogens often remain quiescent and unable to cause disease until ripening begins, emerging at this point into destructive necrotrophic lifestyles that quickly result in fruit decay. Here, we demonstrate that one such pathogen, Botrytis cinerea, actively induces ripening processes to facilitate infections and promote disease in tomato (Solanum lycopersicum). Assessments of ripening progression revealed that B. cinerea accelerated external coloration, ethylene production, and softening in unripe fruit, while mRNA sequencing of inoculated unripe fruit confirmed the corresponding upregulation of host genes involved in ripening processes, such as ethylene biosynthesis and cell wall degradation. Furthermore, an enzyme-linked immunosorbent assay (ELISA)-based glycomics technique used to assess fruit cell wall polysaccharides revealed remarkable similarities in the cell wall polysaccharide changes caused by both infections of unripe fruit and ripening of healthy fruit, particularly in the increased accessibility of pectic polysaccharides. Virulence and additional ripening assessment experiments with B. cinerea knockout mutants showed that induction of ripening depends on the ability to infect the host and break down pectin. The B. cinerea double knockout Δbc polygalacturonase1 Δbc polygalacturonase2 lacking two critical pectin degrading enzymes was incapable of emerging from quiescence even long after the fruit had ripened at its own pace, suggesting that the failure to accelerate ripening severely inhibits fungal survival on unripe fruit. These findings demonstrate that active induction of ripening in unripe tomato fruit is an important infection strategy for B. cinerea.

Transformation of Diffusion and Local Structure of CH4 , CO2 , SO2 and H2 O Mixtures in Graphene Under Wide Temperature and Pressure Range: A Molecular Dynamics Simulation Study.

As a material with high specific surface area and excellent chemical stability, graphene exhibited remarkable adsorption and separation performance as well as a wide range of potential applications. The graphene layer played a significant role in influencing gas transmission. In this study, we employed molecular dynamics simulation to investigate the diffusion characteristics and local structures of a mixed system consisting of CH4 , CO2 , SO2 and H2 O. Additionally, we further examined the transformation of the behavior of these mixtures within graphene layers. The order of diffusion coefficients of the four molecules without graphene was H2 O>SO2 >CO2 ≫CH4 . However, in the double-layer graphene, the order changed to CH4 >CO2 ≫H2 O>SO2 . Higher temperatures and lower pressures were found to facilitate gas diffusion. Temperature and pressure had great effects on the local structures of CH4 , CO2 and SO2 , while their impact on H2 O was limited due to the extensive network of hydrogen bonds formed by H2 O molecules. The statistical results of average coordination number revealed that CH4 tended to aggregate with itself, whereas CO2 and SO2 exhibited a tendency to aggregate with H2 O. The graphene structure enhanced the separation and transportation of CH4 from mixed systems.

A H2O2 Oxidation Approach to Ti3C2/TiO2 for Efficient Photocatalytic Removal of Distinct Organic Pollutants in Water.

To develop versatile photocatalysts for efficient degradation of distinct organic pollutants in water is a continuous pursuit in environment remediation. Herein, we directly oxidize Ti3C2 MXene with hydrogen peroxide to produce C-doped anatase TiO2 nanowires with aggregates maintaining a layered architecture of the MXene. The Ti3C2 MXene provides a titanium source for TiO2, a carbon source for in situ C-doping, and templates for nanowire aggregates. Under UV light illumination, the optimized Ti3C2/TiO2 exhibits a reaction rate constant 1.5 times that of the benchmark P25 TiO2 nanoparticles, toward photocatalytic degradations of trace phenol in water. The mechanism study suggests that photogenerated holes play key roles on the phenol degradation, either directly oxidizing phenol molecules or in an indirect way through oxidizing first the surface hydroxyl groups. The unreacted Ti3C2 MXene, although with trace amounts, is supposed to facilitate electron transfer, which inhibits charge recombination. The unique nanostructure of layered aggregates of nanowires, abundant surface oxygen vacancies arising from the carbon doping, and probably the Ti3C2/TiO2 heterojunction guarantee the high photocatalytic efficiency toward removals of organic pollutants in water. The photocatalyst also exhibits an activity superior to, or at least comparable to, the benchmark P25 TiO2 toward photodegradations for typical persistent organic pollutants of phenol, dye molecule of rhodamine B, antibiotic of tetracycline, pharmaceutical wastewater of ofloxacin, and pesticide of N,N-dimethylformamide, when evaluated in total organic carbon removal.

Fractional exhaled nitric oxide, a potential biomarker for evaluating glucocorticoids treatment and prognosis in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. OBJECTIVE: To investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment. METHODS: This study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data. RESULTS: Different prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation. CONCLUSION: Our findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.

Predictive value of the serum uric acid to high-density lipoprotein cholesterol ratio for culprit plaques in patients with acute coronary syndrome.

BACKGROUND: Hyperuricemia and low level of high-density lipoprotein cholesterol (HDL-C) are both risk factors for coronary artery disease (CAD). The uric acid to HDL-C ratio (UHR) has recently been identified as a new inflammatory and metabolic biomarker. However, the relationship between the UHR and coronary culprit plaques has not been fully investigated in patients with acute coronary syndrome (ACS). METHODS: A total of 346 patients with ACS were enrolled in this study. Culprit lesion characteristics were assessed by optical coherence tomography (OCT). Logistic regression and linear correlation analyses were performed to assess the association between the UHR and culprit plaques. The predictive value of the UHR was investigated by receiver operating characteristic (ROC) curve analysis. RESULTS: The percentages of typical culprit plaques, including ruptures, erosions and thrombi, were greater in the high-UHR subgroup than those in the low-UHR subgroup. A positive relationship was also found between the UHR and diameter stenosis (r = 0.160, P = 0.003) and between the UHR and area stenosis (r = 0.145, P = 0.007). The UHR was found to be independently associated with plaque rupture, erosion and thrombus. Furthermore, ROC analysis suggested that the UHR had a better predictive value than low-density lipoprotein cholesterol. CONCLUSIONS: An elevated UHR level was independently related to the occurrence rate of culprit plaques. The UHR is a simple and easily acquired parameter for detecting culprit plaques in patients with ACS.

Albumin-to-D-dimer ratios: A novel prognostic factor for evaluating first-line chemotherapy efficacy in advanced lung adenocarcinoma patients.

The prognosis of advanced lung adenocarcinoma (LUAD) remains unfavorable, with chemotherapy constituting a primary treatment modality. Discerning the efficacy of chemotherapy for advanced LUAD is imperative. Prior investigations have demonstrated the prognostic value of albumin and D-dimer individually for malignancies; however, the predictive capacity of albumin-to-D-dimer ratios (ADR) for advanced LUAD subjected to first-line platinum-based chemotherapy remains unexplored. A cohort of 313 patients with advanced LUAD was retrospectively examined in this study, spanning from January 2017 to January 2021. ADR threshold values were ascertained via receiver operating characteristic analysis, followed by the evaluation of the association between pretreatment ADR and clinicopathological characteristics, disease control rate (DCR), and overall response rate (ORR) pertinent to first-line chemotherapy. Prognostic factors for progression-free survival (PFS) were determined employing Cox univariate and multivariate analyses. Subsequently, survival data were illustrated utilizing the Kaplan-Meier method and scrutinized through the log-rank test across the entire and subgroup populations. ADR demonstrated a superior area under the curve (AUC) value relative to albumin and D-dimer individually and exhibited enhanced prognostic predictive capability compared to albumin-to-fibrinogen ratios (AFR) for advanced LUAD (AUC: 0.805 vs. 0.640, DeLong test: p<0.001). ADR yielded a cut-off value of 16.608. A greater proportion of non-smokers was observed within the high-ADR group (ADR>16.608) compared to the low-ADR group (ADR≤16.608). Patients in the high-ADR group displayed elevated BMI and Na+ levels and reduced neutrophil count, monocyte count, globulin, and alkaline phosphatase (all p<0.05). Notably, the high-ADR group exhibited heightened DCR (96.7% vs. 89.2%, p=0.008) and ORR rates (70.1% vs. 51.0%, p=0.001) relative to the low-ADR group. Multivariate analysis outcomes indicated that high ADR constituted an independent risk factor for PFS (hazard ratio: 0.24, p<0.001). Furthermore, patients in the high-ADR cohort displayed a significantly prolonged median PFS (254 vs. 142 days, p<0.0001) compared to their low-ADR counterparts. In subpopulations exhibiting favorable implications for PFS, as determined by multivariate analysis, high-ADR patients consistently demonstrated extended PFS durations relative to the low-ADR group (all p<0.0001). Collectively, our findings suggest that ADR constitutes a novel and promising prognostic indicator for advanced LUAD patients, surpassing the accuracy of albumin and D-dimer individually and AFR. ADR thus serves as a potent instrument for assessing treatment effects and PFS in advanced LUAD patients undergoing first-line chemotherapy.

ASPP2 suppresses tumour growth and stemness characteristics in HCC by inhibiting Warburg effect via WNT/ß-catenin/HK2 axis.

Abnormal energy metabolism is one of the characteristics of tumours. In the last few years, more and more attention is being paid to the role and regulation of tumour aerobic glycolysis. Cancer cells display enhanced aerobic glycolysis, also known as the Warburg effect, whereby tumour cells absorb glucose to produce a large amount of lactic acid and energy under aerobic conditions to favour tumour proliferation and metastasis. In this study, we report that the haploinsufficient tumour suppressor ASPP2, can inhibit HCC growth and stemness characteristics by regulating the Warburg effect through the WNT/ß-catenin pathway. we performed glucose uptake, lactate production, pyruvate production, ECAR and OCR assays to verify ASPP2 can inhibit glycolysis in HCC cells. The expression of ASPP2 and HK2 was significantly inversely correlated in 80 HCC tissues. Our study reveals downregulation of ASPP2 can promote the aerobic glycolysis metabolism pathway, increasing HCC proliferation, glycolysis metabolism, stemness and drug resistance. This ASPP2-induced inhibition of glycolysis metabolism depends on the WNT/ß-catenin pathway. ASPP2-regulated Warburg effect is associated with tumour progression and provides prognostic value. and suggest that may be promising as a new therapeutic strategy in HCC.

Oryza sativa PECTIN DEFECTIVE TAPETUM1 affects anther development through a pectin-mediated signaling pathway in rice.

Galacturonosyltransferase (GalAT) is required for the synthesis of pectin, an important component of plant cell walls that is also involved in signal transduction. Here, we describe the rice (Oryza sativa) male-sterile mutant O. sativa pectin-defective tapetum1 (ospdt1), in which GalAT is mutated. The ospdt1 mutant exhibited premature programmed cell death (PCD) of the tapetum and disordered pollen walls, resulting in aborted pollen grains. Pectin distribution in the anther sac was comparable between the mutant and the wild-type, suggesting that the structural pectin was not dramatically affected in ospdt1. Wall-associated kinases are necessary for the signal transduction of pectin, and the intracellular distribution of O. sativa indica WALL-ASSOCIATED KINASE1 (OsiWAK1), which binds pectic polysaccharides to its extracellular domain, was affected in ospdt1. OsiWAK1 RNA interference lines exhibited earlier tapetal PCD, similar to ospdt1. Furthermore, overexpression of OsiWAK1 in ospdt1 lines partially rescued the defects observed in ospdt1, suggesting that OsiWAK1 plays pivotal roles in the function of OsPDT1. These results suggest that the mutation of OsPDT1 does not dramatically affect structural pectin but affects components of the pectin-mediated signaling pathway, such as OsiWAK1, and causes male sterility.

POLLEN WALL ABORTION 1 is essential for pollen wall development in rice.

The integrity of pollen wall structures is essential for pollen development and maturity in rice (Oryza sativa L.). In this study, we isolated and characterized the rice male-sterile mutant pollen wall abortion 1 (pwa1), which exhibits a defective pollen wall (DPW) structure and has sterile pollen. Map-based cloning, genetic complementation, and gene knockout experiments revealed that PWA1 corresponds to the gene LOC_Os01g55094 encoding a coiled-coil domain-containing protein. PWA1 localized to the nucleus, and PWA1 was expressed in the tapetum and microspores. PWA1 interacted with the transcription factor TAPETUM DEGENERATION RETARDATION (TDR)-INTERACTING PROTEIN2 (TIP2, also named bHLH142) in vivo and in vitro. The tip2-1 mutant, which we obtained by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated gene editing, showed delayed tapetum degradation, sterile pollen, and DPWs. We determined that TIP2/bHLH142 regulates PWA1 expression by binding to its promoter. Analysis of the phenotype of the tip2-1 pwa1 double mutant indicated that TIP2/bHLH142 functions upstream of PWA1. Further studies suggested that PWA1 has transcriptional activation activity and participates in pollen intine development through the ß-glucosidase Os12BGlu38. Therefore, we identified a sterility factor, PWA1, and uncovered a regulatory network underlying the formation of the pollen wall and mature pollen in rice.

Association of the time course of Chinese visceral adiposity index accumulation with cardiovascular events in patients with hypertension.

BACKGROUND: The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension. METHODS: This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006-2007, 2010-2011, and 2014-2015) and who were free of myocardial infarction and stroke before 2014. The cumCVAI was calculated as the weighted sum of the mean CVAI for each time interval (value × time). The time course of CVAI accumulation was categorized by splitting the overall accumulation into early (cumCVAI06 - 10) and late (cumCVAI10 - 14) accumulation, or the slope of CVAI versus time from 2006 to 2014 into positive and negative. RESULTS: During the 6.59-year follow-up period, 1,184 new-onset CVD events were recorded. After adjusting for confounding variables, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD were 1.35 (1.13-1.61) in the highest quartile of cumCVAI, 1.35 (1.14-1.61) in the highest quartile of the time-weighted average CVAI, 1.26 (1.12-1.43) in those with a cumulative burden > 0, and 1.43 (1.14-1.78) for the group with a 10-year exposure duration. When considering the time course of CVAI accumulation, the HR (95% CI) for CVD was 1.33 (1.11-1.59) for early cumCVAI. When considering the combined effect of cumCVAI accumulation and its time course, the HR (95% CI) for CVD was 1.22 (1.03-1.46) for cumCVAI ≥ median with a positive slope. CONCLUSIONS: In this study, incident CVD risk depended on both long-term high cumCVAI exposure and the duration of high CVAI exposure among patients with hypertension. Early CVAI accumulation resulted in a greater risk increase than later CVAI accumulation, emphasizing the importance of optimal CVAI control in early life.

OsMYB103 is essential for tapetum degradation in rice.

KEY MESSAGE: OsMYB103 positively regulates tapetum degradation, and functions downstream of TDR and upstream of EAT1 and PTC1. The precise regulation of programmed cell death (PCD) of the tapetum is crucial for the development of anthers and pollen in rice. In this study, we isolated and identified a male-sterile mutant of rice, osmyb103, which exhibited delayed tapetum degradation and defective mature pollen. Map-based cloning and genetic complementation revealed that OsMYB103 corresponded to the gene LOC_Os04g39470 and encoded a R2R3 MYB transcription factor. OsMYB103 was localized in the nucleus and was expressed preferentially in the tapetal cells and microspores of the anther. OsMYB103 regulated the expression of two transcription factors, ETERNAL TAPETUM 1 (EAT1) and PERSISTENT TAPETAL CELL 1 (PTC1), both of which regulated tapetum degradation positively. Moreover, the expression of OsMYB103 was directly regulated by the additional positive regulator of tapetum degradation TAPETUM DEGENERATION RETARDATION (TDR) and was able to interact with it. Genetic evidence confirmed that OsMYB103 acted upstream of EAT1. The results show that OsMYB103 is a positive regulator of tapetum degradation in rice. These findings provide a better understanding of the regulatory network that underlies degradation of the tapetum in rice.

OsFLA1 encodes a fasciclin-like arabinogalactan protein and affects pollen exine development in rice.

KEY MESSAGE: OsFLA1 positively regulates pollen exine development, and locates in the cellular membrane. Arabinogalactan proteins are a type of hydroxyproline-rich glycoprotein that are present in all plant tissues and cells and play important roles in plant growth and development. Little information is available on the participation of fasciclin-like arabinogalactan proteins in sexual reproduction in rice. In this study, a rice male-sterile mutant, osfla1, was isolated from an ethylmethanesulfonate-induced mutant library. The osfla1 mutant produced withered, shrunken, and abortive pollen. The gene OsFLA1 encoded a FLA protein and was expressed strongly in the anthers in rice. Subcellular localization showed that OsFLA1 was located in the cellular membrane. In the osfla1 mutant, abnormal Ubisch bodies and a discontinuous nexine layer of the microspore wall were observed, which resulted in pollen abortion and ultimately in male sterility. The results show the important role that OsFLA1 plays in male reproductive development in rice.

Alkyl-benzofuran dimers from Eupatorium chinense with insulin-sensitizing and anti-inflammatory activities.

Five new racemic alkyl-benzofuran dimers, (±)-dieupachinins I-M (1-5), were isolated from the root tubers of Eupatorium chinense, a well-known traditional Chinese medicine for the treatment of diphtheria in Guangdong province. The structures of these compounds, especially the first examples of 12,10'-epoxy dimer dieupachinin I (1), 12-nor-dimer dieupachinin J (2), and 12,12'-dinor-dimer dieupachinin K (3), were elucidated by spectroscopic data analysis. Chiral resolution were further carried out on a cellulose column by HPLC, and compounds 2-5 were successfully separated into two enantiomers, respectively. The absolute configurations of (+)-(2-5) and (-)-(2-5) were established by theoretical ECD calculation. All the compounds were evaluated for insulin-stimulated glucose uptake in C2C12 myotubes and (±)-dieupachinin I (1) exhibited the best activity. Compound 1 enhanced insulin-stimulated glucose uptake via activating the insulin receptor substrate 1/protein kinase B/glycogen synthase kinase-3ß signaling pathway. Moreover, all the isolates were tested for their nitric oxygen (NO) inhibitory effects in lipopolysaccharide-treated RAW264.7 macrophages, and compounds (±)-1, (±)-2, and (±)-4 showed promising inhibitory effects with IC50 values of 6.42 ± 1.85, 6.29 ± 1.94, and 16.03 ± 2.07 µM, respectively. (±)-Dieupachinin I (1) again dose-dependently suppressed LPS-induced expression of inducible NO synthase and nuclear translocation of p65.

BMI differences among in-hospital management and outcomes in patients with atrial fibrillation: findings from the Care for Cardiovascular Disease project in China.

BACKGROUND: Underweight or obese status influences the prognosis of atrial fibrillation (AF). However, the association between stratification of body mass index (BMI) and in-hospital outcomes in patients with AF, remains lacking in China. METHODS: Using data from the Improving Care for Cardiovascular Disease in China-AF project, which was launched in February 2015 and recruited 150 hospitals in China, we compared characteristics, in-hospital treatments and clinical outcomes among the stratifications of BMI for Asians. RESULTS: A total of 15,867 AF patients with AF were enrolled, including 830 (5.23%) underweight, 4965 (31.29%) with normal weight, 3716 (23.42%) overweight, 5263 (33.17%) obese class I and 1093 (6.89%) obese class II participants. Compared with normal weight patients, underweight, overweight, and obese patients showed increased percentages of CHADS2 scores (3-6) and CHA2DS2-VASc scores (5-9). During hospitalization, overweight or obese patients showed greater use of rhythm control medications, anticoagulant drugs, and intervention therapies than underweight-normal weight patients. In adjusted logistic models, BMI was a strong predictor of in-hospital mortality. Especially, underweight BMI was associated with higher incidence of in-hospital mortality, with an adjusted odds ratio of 2.08 (95% confidence interval, 1.56-4.46; p = 0.04) than overweight and obese BMI. CONCLUSIONS: Asian patients with AF and high BMI received more medical treatments and presented less adverse in-hospital outcomes compared with those with underweight-normal weight. Although low BMI may be associated with other comorbidities and advanced age, underweight BMI retained a negative correlation with all-cause mortality in the patients with AF during hospitalization.

Bacterial succession in epiphytic biofilms and deciduous layer sediments during Hydrilla verticillata decay: A field investigation.

Submersed macrophytes decay is an important natural process and has important role in mass and energy flow in aquatic ecosystems. However, little is known about the dynamical changes in nutrients release and bacterial community during submersed macrophyte decay in natural environment. In this study, a field observation was conducted in a wetland dominated with Hydrilla verticillata for 36 days. Increase of H2O2 and malondialdehyde (MDA) content and decrease of soluble proteins concentration were detected in leaves during H. verticillata decay. Meanwhile, ammonium-N, soluble microbial products (SMP) and TOC concentration increased in overlying water. According to bacterial 16S rRNA Illumina sequencing analysis, the Shannon values were lower in epiphytic biofilms than deciduous layer sediments. The relative abundances of Proteobacteria, Cyanobacteria and Actinobacteria were higher in epiphytic biofilms than in deciduous layer sediments (P < 0.05). Co-occurrence network analyses showed that a total of 578 and 845 pairs of correlations (|r| > 0.6) were identified from 122 and 112 genera in epiphytic biofilms and deciduous layer sediments, respectively. According to co-occurrence patterns, eight hubs were mainly from phyla Proteobacteria, Acidobacteria and Parcubacteria in epiphytic biofilms; while 37 hubs from the 14 phyla (Proteobacteria, Bacteroidetes, Acidobacteria, Chloroflexi, et al.) were detected in deciduous layer sediments. Our results indicate that bacterial community in deciduous layer sediments was more susceptible than in epiphytic biofilms during decay process. These data highlight the role of microbial community in deciduous layer sediments on nutrients removal during H. verticillata decay and will provide useful information for wetland management.

Angiotensin II deteriorates advanced atherosclerosis by promoting MerTK cleavage and impairing efferocytosis through the AT1R/ROS/p38 MAPK/ADAM17 pathway.

Vulnerable plaques in advanced atherosclerosis have defective efferocytosis. The role of ANG II in the progression of atherosclerosis is not fully understood. Herein, we investigated the effects and the underlying mechanisms of ANG II on macrophage efferocytosis in advanced atherosclerosis. ANG II decreased the surface expression of Mer tyrosine kinase (MerTK) in macrophages through a disintegrin and metalloproteinase17 (ADAM17)-mediated shedding of the soluble form of MerTK (sMer) in the medium, which led to efferocytosis suppression. ANG II-activated ADAM17 required reactive oxygen species (ROS) and p38 MAPK phosphorylation. Selective angiotensin II type 1 receptor (AT1R) blocker losartan suppressed ROS production, and ROS scavenger N-acetyl-l-cysteine (NAC) prevented p38 MAPK phosphorylation. In addition, mutant MERTKΔ483-488 was resistant to ANG II-induced MerTK shedding and efferocytosis suppression. The advanced atherosclerosis model that is characterized by larger necrotic cores, and less collagen content was established by feeding apolipoprotein E knockout (ApoE-/-) mice with a high-fat diet for 16 wk. NAC and losartan oral administration prevented atherosclerotic lesion progression. Meanwhile, the inefficient efferocytosis represented by decreased macrophage-associated apoptotic cells and decreased MerTK+CD68+double-positive macrophages in advanced atherosclerosis were prevented by losartan and NAC. Additionally, the serum levels of sMer were increased and positively correlated with the upregulated levels of ANG II in acute coronary syndrome (ACS) patients. In conclusion, ANG II promotes MerTK shedding via AT1R/ROS/p38 MAPK/ADAM17 pathway in macrophages, which led to defective efferocytosis and atherosclerosis progression. Defining the molecular mechanisms of defective efferocytosis may provide a promising prognosis and therapy for ACS patients.

Structure-Function Analysis of Immune Receptor AtRLP23 with Its Ligand nlp20 and Coreceptors AtSOBIR1 and AtBAK1.

Pattern-triggered immunity is an inherent feature of the plant immune system. Recognition of either microbe-derived surface structures (patterns) or of plant materials released due to the deleterious impact of microbial infection is brought about by plasma membrane pattern recognition receptors (PRRs). PRRs composed of leucine-rich repeat (LRR) ectodomains are thought to mediate sensing of proteinaceous patterns and to initiate signaling cascades culminating in the activation of generic plant defenses. In contrast to LRR receptor kinases, LRR receptor proteins (LRR-RPs) lack a cytoplasmic kinase domain for initiation of downstream signal transduction. LRR-RPs form heteromeric constitutive, ligand-independent complexes with coreceptor SOBIR1. Upon ligand binding to LRR-RPs, recruitment of coreceptor SERK3/BAK1 results in formation of a ternary PRR complex. Structure-function analysis of LRR-RP-type PRRs is missing. AtRLP23 constitutes an LRR-RP PRR that mediates recognition of a peptide motif (nlp20) found in numerous bacterial, fungal, and oomycete necrosis and ethylene-inducing peptide 1-like proteins (NLPs). We here report the use of a series of AtRLP23 variants to decipher subdomains required for ligand binding and interaction with coreceptors AtSOBIR1 and AtBAK1, respectively. Deletion of LRR1 or LRR3 subdomains efficiently abrogated the ability of AtRLP23 receptor variants to confer nlp20 pattern sensitivity, to bind nlp20, and to recruit AtBAK1 into a ternary PRR complex. This suggests that the very N-terminal part of the AtRLP23 ectodomain is crucial for receptor function. Deletion of the intracellular 17-amino-acid tail of AtRLP23 reduced but did not abolish receptor function, suggesting an auxiliary role of this domain in receptor function. We further found that interaction of AtRLP23 and other LRR-RP-type PRRs with AtSOBIR1 does not require the AtRLP23 LRR ectodomain but is brought about by a GxxxG protein dimerization motif in the transmembrane domain and a stretch of negatively charged glutamic acid residues in the outer juxtamembrane domain of the receptor. Further, AtRLP23 levels were found to be unaltered in Atsobir1-1 mutant genotypes, suggesting that AtSOBIR1 does not act as a protein scaffold in stabilizing LRR-RP-type PRRs in Arabidopsis.

Comparing Arabidopsis receptor kinase and receptor protein-mediated immune signaling reveals BIK1-dependent differences.

Pattern recognition receptors (PRRs) sense microbial patterns and activate innate immunity against attempted microbial invasions. The leucine-rich repeat receptor kinases (LRR-RK) FLS2 and EFR, and the LRR receptor protein (LRR-RP) receptors RLP23 and RLP42, respectively, represent prototypical members of these two prominent and closely related PRR families. We conducted a survey of Arabidopsis thaliana immune signaling mediated by these receptors to address the question of commonalities and differences between LRR-RK and LRR-RP signaling. Quantitative differences in timing and amplitude were observed for several early immune responses, with RP-mediated responses typically being slower and more prolonged than those mediated by RKs. Activation of RLP23, but not FLS2, induced the production of camalexin. Transcriptomic analysis revealed that RLP23-regulated genes represent only a fraction of those genes differentially expressed upon FLS2 activation. Several positive and negative regulators of FLS2-signaling play similar roles in RLP23 signaling. Intriguingly, the cytoplasmic receptor kinase BIK1, a positive regulator of RK signaling, acts as a negative regulator of RP-type immune receptors in a manner dependent on BIK1 kinase activity. Our study unveiled unexpected differences in two closely related receptor systems and reports a new negative role of BIK1 in plant immunity.