Colletotrichum fructicola co-opts cytotoxic ribonucleases that antagonize host competitive microorganisms to promote infection.

Phytopathogens secrete numerous molecules into the environment to establish a microbial niche and facilitate host infection. The phytopathogenic fungus Colletotrichum fructicola, which causes pear anthracnose, can colonize different plant tissues like leaves and fruits, which are occupied by a diversity of microbes. We speculate that this fungus produces antimicrobial effectors to outcompete host-associated competitive microorganisms. Herein, we identified two secreted ribonucleases, CfRibo1 and CfRibo2, from the C. fructicola secretome. The two ribonucleases both possess ribonuclease activity and showed cytotoxicity in Nicotianan benthamiana without triggering immunity in an enzymatic activity-dependent manner. CfRibo1 and CfRibo2 recombinant proteins exhibited toxicity against Escherichia coli, Saccharomyces cerevisiae, and, importantly, the phyllosphere microorganisms isolated from the pear host. Among these isolated microbial strains, Bacillus altitudinis is a pathogenic bacterium causing pear soft rot. Strikingly, CfRibo1 and CfRibo2 were found to directly antagonize B. altitudinis to facilitate C. fructicola infection. More importantly, CfRibo1 and CfRibo2 functioned as essential virulence factors of C. fructicola in the presence of host-associated microorganisms. Further analysis revealed these two ribonucleases are widely distributed in fungi and are undergoing purifying selection. Our results provide the first evidence of antimicrobial effectors in Colletotrichum fungi and extend the functional diversity of fungal ribonucleases in plant-pest-environment interactions. IMPORTANCE: Colletotrichum fructicola is emerging as a devastating pathogenic fungus causing anthracnose in various crops in agriculture, and understanding how this fungus establishes successful infection is of great significance for anthracnose disease management. Fungi are known to produce secreted effectors as weapons to promote virulence. Considerable progress has been made in elucidating how effectors manipulate plant immunity; however, their importance in modulating environmental microbes is frequently neglected. The present study identified two secreted ribonucleases, CfRibo1 and CfRibo2, as antimicrobial effectors of C. fructicola. These two proteins both possess toxicity to pear phyllosphere microorganisms, and they efficiently antagonize competitive microbes to facilitate the infection of pear hosts. This study represents the first evidence of antimicrobial effectors in Colletotrichum fungi, and we consider that CfRibo1 and CfRibo2 could be targeted for anthracnose disease management in diverse crops in the future.

Connectome gradient dysfunction contributes to white matter hyperintensity-related cognitive decline.

BACKGROUND: Although white matter hyperintensity (WMH) is closely associated with cognitive decline, the precise neurobiological mechanisms underlying this relationship are not fully elucidated. Connectome studies have identified a primary-to-transmodal gradient in functional brain networks that support the spectrum from sensation to cognition. However, whether connectome gradient structure is altered as WMH progresses and how this alteration is associated with WMH-related cognitive decline remain unknown. METHODS: A total of 758 WMH individuals completed cognitive assessment and resting-state functional MRI (rs-fMRI). The functional connectome gradient was reconstructed based on rs-fMRI by using a gradient decomposition framework. Interrelations among the spatial distribution of WMH, functional gradient measures, and specific cognitive domains were explored. RESULTS: As the WMH volume increased, the executive function (r = -0.135, p = 0.001) and information-processing speed (r = -0.224, p = 0.001) became poorer, the gradient range (r = -0.099, p = 0.006), and variance (r = -0.121, p < 0.001) of the primary-to-transmodal gradient reduced. A narrower gradient range (r = 0.131, p = 0.001) and a smaller gradient variance (r = 0.136, p = 0.001) corresponded to a poorer executive function. In particular, the relationship between the frontal/occipital WMH and executive function was partly mediated by gradient range/variance of the primary-to-transmodal gradient. CONCLUSIONS: These findings indicated that WMH volume, the primary-to-transmodal gradient, and cognition were interrelated. The detrimental effect of the frontal/occipital WMH on executive function was partly mediated by the decreased differentiation of the connectivity pattern between the primary and transmodal areas.

Expression of CXCL8 and its relationship with prognosis in patients with non-small cell lung cancer.

To determine the expression of chemokine 8 (CXCL8) in non-small cell lung cancer (NSCLC) patients and analyze its correlation with tumor characteristics and patient prognosis. We conducted a retrospective analysis of 149 NSCLC patients treated between January 2016 and April 2018, measuring serum CXCL8 expression upon admission or prior to treatment. The clinical characteristics, including lymph node metastasis and staging, based on CXCL8 expression levels, were analyzed. Receiver Operating Characteristic (ROC) curves was drawn to assess its predictive value for lymph node metastasis and staging in NSCLC patients. Furthermore, the Kaplan-Meier curve was plotted to assess the impact of CXCL8 on 5-year survival in NSCLC Patients. NSCLC patients exhibited significantly higher serum CXCL8 levels than those with benign tumors (P<0.001), with the high CXCL8 expression group showing a higher incidence of lymph node metastasis or stage III NSCLC (P<0.01). CXCL8 was identified as an independent predictor of lymph node metastasis (AUC=0.730) and higher TNM stage (AUC=0.708), as well as a validated biomarker for predicting five-year survival in NSCLC patients. This study highlights the strong association between CXCL8 expression in NSCLC and patient prognosis, particularly regarding lymph node metastasis and clinical staging, suggesting the need for further research to explore CXCL8's specific role in the tumor microenvironment and its impact on different NSCLC subtypes.

Comparisons of different general anesthetic techniques on immune function in patients undergoing flap reconstruction for oral cancer.

BACKGROUND: Anesthetic-induced immunosuppression is of particular interest in tumor surgery. This study aimed to investigate the influence of the 4 most common general anesthetic techniques on immune function in patients undergoing flap reconstruction for oral cancer. METHODS: 116 patients were randomly divided into 4 groups. Patients in group S were given sevoflurane-based anesthesia. Group P was administered propofol-based anesthesia. The SD group received sevoflurane combined with dexmedetomidine anesthesia. The propofol combined with dexmedetomidine anesthesia (PD) group received PD. Blood samples were obtained at 5 time points: baseline (T0), 1 hour after the start of the operation (T1), end of the operation (T2), 24 hours (T3), and 48 hours (T4) after the operation. Lymphocyte subsets (including CD3+, CD4+, CD8+, and B lymphocytes) and dendritic cells were analyzed by flow cytometry. Blood glucose, norepinephrine, and cortisol levels were measured using ELISA and a blood gas analyzer respectively. RESULTS: In total, 107 patients were included in the final analysis. Immunological indicators, except CD8+ counts, were all decreased in groups S, P, and SD at T1-4 compared with the baseline value, and the counts of CD3+, CD4+, and dendritic cells, as well as CD4+/CD8+ ratios, were significantly higher in the PD group than in the S, P, and SD at T1-3 (P < .05). There were no significant differences between groups P and SD at any observation time point. Intraoperative stress indices, including norepinephrine and cortisol levels, were significantly lower in the PD group than in the other 3 groups at T1-2 (P < .05). CONCLUSION: These findings suggest that PD as a probably optimal choice can alleviate immunosuppression in patients undergoing flap reconstruction for oral cancer.

Two polyketide synthase genes VpPKS10 and VpPKS33 regulated by VpLaeA are essential to the virulence of Valsa pyri.

Valsa pyri, the causal agent of pear canker disease, typically induces cankers on the bark of infected trees and even leads to tree mortality. Secondary metabolites (SMs) produced by pathogenic fungi play a crucial role in the pathogenic process. In this study, secondary metabolic regulator VpLaeA was identified in V. pyri. VpLaeA was found to strongly affect the pathogenicity, fruiting body formation and toxicity of SMs of V. pyri. Additionally, VpLaeA was also found to be required for the response of V. pyri to some abiotic stresses. Transcriptome data analysis revealed that many of differentially expressed genes were involved in the secondary metabolite biosynthesis (SMB). Among them, about one third of SMB core genes were regulated by VpLaeA at different periods. Seven differentially expressed SMB core genes (VpPKS9, VpPKS10, VpPKS33, VpNRPS6, VpNRPS7, VpNRPS16, and VpNRPS17) were selected for knockout. Two modular polyketide synthase (PKS) genes (VpPKS10 and VpPKS33), which were closely related to the virulence of V. pyri from the above seven genes were identified. Notably, VpPKS10 and VpPKS33 also affected the production of fruiting body of V. pyri, but didn't participate in the resistance of V. pyri to abiotic stresses. Overall, this study demonstrates the multifaceted biological functions of VpLaeA in V. pyri, and identifies two toxicity-associated PKS genes in Valsa species fungi for the first time.

Insight Into the Degradation Pathways of an AAV9.

The use of recombinant adeno-associated virus (AAV) vectors is a popular choice for in vivo gene therapy, with hundreds of ongoing clinical trials targeting various genetic diseases. However, due to limited material availability and the complexity of AAV structure, there is a critical lack of comprehensive studies on AAV degradation pathways. In this study, we intended to elucidate the degradation pathways for a model AAV9 with GFP as the transgene under relevant stressed conditions. We assessed a diverse set of critical quality attributes and examined the overall impact of various stresses on transgene expression. This assessment revealed various degradation mechanisms of AAV9 and demonstrated the potential risk of a base formulation in causing AAV9 instability and potency loss under thermal stress at 25 and 40 °C while maintaining stability under freeze-thaw stress, interfacial stress due to membrane filtration, and short-term storage of up to 4 weeks at 5 °C.

Evaluation of Stripe Rust Resistance and Chip Detection Resistance Genes in 286 Xinjiang Wheat Cultivars and Breeding Lines.

Wheat stripe rust is a destructive disease worldwide, caused by Puccinia striiformis f. sp. tritici (Pst). Resistance breeding is the most effective method of controlling stripe rust. Xinjiang is a relatively independent epidemic region of wheat stripe rust in China. In recent years, wheat stripe rust in this area has shown an upward trend. Therefore, the purpose of this study was to evaluate the resistance level of wheat cultivars (lines) to the prevalent Pst races and determine the genetic background of stripe rust resistance genes in Xinjiang. Six predominant Pst races in China were used to study resistance of 286 wheat cultivars (lines) at both seedling under controlled conditions and adult-plant stages under field conditions. In the seedling tests, 175 (61.19%) entries were resistant to races CYR23, 125 (43.71%) to CYR29, 153 (53.50%) to CYR31, 88 (30.77%) to CYR32, 174 (60.84%) to CYR33, and 98 (34.27%) to CYR34. Among the resistant entries, 23 (8.04%) were resistant to all six races. In the field test, 135 (47.20%) entries were resistant to the tested mixed races. Through comparing the responses in the seedling and adult-plant stages, 109 (38.11%) entries were found to have adult-plant resistance (APR), and 14 (4.90%) entries have all-stage resistance (ASR). The 286 wheat entries were also tested using a wheat breeder chip containing 12 Yr resistance loci. Among these entries, 44 (15.38%) were found to have single gene, 221 (77.27%) have two or more genes, and 21 (7.34%) have none of the 12 genes, including 144 (50.35%) with Yr30 and 5 (1.75%) with YrSP. Entries with two or more genes have stronger resistance to Pst. Overall, the majority of entries have all-stage and/or adult-plant resistance, but their genes for resistance in addition to the 12 tested Yr genes need to be determined. It is also necessary to introduce more effective resistance genes in the breeding programs to improve stripe rust resistance in wheat cultivars in Xinjiang.

Rapid identification and quantitative analysis of malachite green in fish via SERS and 1D convolutional neural network.

Rapid and quantitative detection of malachite green (MG) in aquaculture products is very important for safety assurance in food supply. Here, we develop a point-of-care testing (POCT) platform that combines a flexible and transparent surface-enhanced Raman scattering (SERS) substrate with deep learning network for achieving rapid and quantitative detection of MG in fish. The flexible and transparent SERS substrate was prepared by depositing silver (Ag) film on the polydimethylsiloxane (PDMS) film using laser molecular beam epitaxy (LMBE) technique. The wrinkled Ag NPs@PDMS film exhibits high SERS activity, excellent reproducibility and good mechanical stability. Additionally, the fast in situ detection of MG residues onfishscales was achieved by using the wrinkled Ag NPs/PDMS film and a portable Raman spectrometer, with a minimum detectable concentration of 10-6 M. Subsequently, a one-dimensional convolutional neural network (1D CNN) model was constructed for rapid quantification of MG concentration. The results demonstrated that the 1D CNN quantitative analysis model possessed superior predictive performance, with a coefficient of determination (R2) of 0.9947 and a mean squared error (MSE) of 0.0104. The proposed POCT platform, integrating a transparent flexible SERS substrate, a portable Raman spectrometer and a 1D CNN model, provides an efficient strategy for rapid identification and quantitative analysis of MG in fish.

VmRDR2 of Valsa mali mediates the generation of VmR2-siR1 that suppresses apple resistance by RNA interference.

Cross-kingdom RNA interference (RNAi) is a crucial mechanism in host-pathogen interactions, with RNA-dependent RNA polymerase (RdRP) playing a vital role in signal amplification during RNAi. However, the role of pathogenic fungal RdRP in siRNAs generation and the regulation of plant-pathogen interactions remains elusive. Using deep sequencing, molecular, genetic, and biochemical approaches, this study revealed that VmRDR2 of Valsa mali regulates VmR2-siR1 to suppress the disease resistance-related gene MdLRP14 in apple. Both VmRDR1 and VmRDR2 are essential for the pathogenicity of V. mali in apple, with VmRDR2 mediating the generation of endogenous siRNAs, including an infection-related siRNA, VmR2-siR1. This siRNA specifically degrades the apple intracellular LRR-RI protein gene MdLRP14 in a sequence-specific manner, and overexpression of MdLRP14 enhances apple resistance against V. mali, which can be suppressed by VmR2-siR1. Conversely, MdLRP14 knockdown reduces resistance. In summary, this study demonstrates that VmRDR2 contributes to the generation of VmR2-siR1, which silences the host's intracellular LRR protein gene, thereby inhibiting host resistance. These findings offer novel insights into the fungi-mediated pathogenicity mechanism through RNAi.

Curvature-Insensitive Transparent Surface-Enhanced Raman Scattering Substrate Based on Large-Area Ag Nanoparticle-Coated Wrinkled Polystyrene/Polydimethylsiloxane Film for Reliable In Situ Detection.

Flexible and transparent surface-enhanced Raman scattering (SERS) substrates have attracted considerable attention for their ability to enable the direct in situ detection of analytes on curved surfaces. However, the curvature of an object can impact the signal enhancement of SERS during the measurement process. Herein, we propose a simple approach for fabricating a curvature-insensitive transparent SERS substrate by depositing silver nanoparticles (Ag NPs) onto a large-area wrinkled polystyrene/polydimethylsiloxane (Ag NP@W-PS/PDMS) bilayer film. Using rhodamine 6G (R6G) as a probe molecule, the optimized Ag NP@W-PS/PDMS film demonstrates a high analytical enhancement factor (AEF) of 4.83 × 105, excellent uniformity (RSD = 7.85%) and reproducibility (RSD = 3.09%), as well as superior mechanical flexibility. Additionally, in situ measurements of malachite green (MG) on objects with diverse curvatures, including fish, apple, and blueberry, are conducted using a portable Raman system, revealing a consistent SERS enhancement. Furthermore, a robust linear relationship (R2 ≥ 0.990) between Raman intensity and the logarithmic concentration of MG detected from these objects is achieved. These results demonstrate the tremendous potential of the developed curvature-insensitive SERS substrate as a point-of-care testing (POCT) platform for identifying analytes on irregular objects.

Gold nanourchin on multiple-point dielectrode for glucose biosensing by current-potential measurement.

Gestational diabetes (GD) is a condition characterized by elevated blood sugar levels during pregnancy. GD poses various health risks, such as serious birth injuries, the need for cesarean delivery, and the necessity of newborn care. Monitoring glucose levels is essential for ensuring safe delivery and reducing the risks to both the mother and fetus. Various sensors are readily available for monitoring glucose levels, and researchers are continually working to develop highly sensitive glucose sensors. This research aimed to develop a gold nanourchin (AuNU)-hybrid biosensor for quantifying glucose on a multi-point electrode sensor. Glucose oxidase (GOx) was attached to the AuNU and seeded on the sensing surface using an amine linker. The current-potential (1-2 V at 0.1 V sweep) was recorded for the GOx-glucose interaction, with a limit of detection of 560 µM and a regression coefficient (R2) of 0.9743 [y = 0.9106x - 0.9953] on the linear curve. The sensitivity was estimated to be 3.5 mAcm-2M-1. Furthermore, control experiments with galactose, sucrose, and fructose did not yield an increase in current-potential, confirming specific glucose detection. This experiment helps in monitoring glucose levels to manage conditions associated with GD.

Longitudinal association between accelerometer-derived rest-activity rhythm and atherosclerotic cardiovascular disease.

OBJECTIVE: Rest-activity rhythm is an essential behavior for human health. However, the association between rest-activity rhythm and atherosclerotic cardiovascular disease (ASCVD) risk remains unclear. Therefore, this study aimed to elucidate the association. METHODS: This study included 87,039 participants from the UK Biobank who had 7-day accelerometry data and were free of ASCVD at baseline. Relative amplitude was calculated as the difference between the most active continuous 10-h period (M10) and the least active continuous 5-h period (L5) in 24 h, and lower relative amplitude indicated the disruption of rest-activity rhythm. Cox proportional hazard model was used to examine the association of relative amplitude with ASCVD. Further, the linear association between relative amplitude and arterial stiffness measurements, including arterial stiffness index (ASI) and carotid intima-media thickness (cIMT), was examined. RESULTS: During a mean follow-up period of 6.80 ± 1.10 years, 2798 ASCVD cases were identified. A dose-response relationship was observed between relative amplitude and ASCVD risk (P for trend<0.001). The adjusted hazard ratio, for the highest vs the lowest quintile of relative amplitude, was 1.54 (95 % confidence interval: 1.31, 1.79). Further, we found significant association of lower relative amplitude with ASI and cIMT. The onset timing of M10 at ≤06:00, 09:00, 10:00, or ≥11:00, as opposed to the reference time of 07:00, was associated with higher ASCVD risk. CONCLUSIONS: Low rest-activity rhythm amplitude was associated with a higher risk of ASCVD. Rest-activity rhythm amplitude may provide a method to identify individuals at risk of ASCVD in public health and clinical practice.

Enhanced Fenton-like catalysis via interfacial regulation of g-C3N4 for efficient aromatic organic pollutant degradation.

For the efficient degradation of organic pollutants with the goal of reducing the water environment pollution, we employed an alkaline hydrothermal treatment on primeval g-C3N4 to synthesize a hydroxyl-grafted g-C3N4 (CN-0.5) material, from which we engineered a novel Fenton-like catalyst, known as Cu-CN-0.5. The introduction of numerous hydroxyl functional groups allowed the CN-0.5 substrate to stably fix active copper oxide particles through surface complexation, resulting in a low Cu leaching rate during a Cu-CN-0.5 Fenton-like process. A sequence of characterization techniques and theoretical calculations uncovered that interfacial complexation induced charge redistribution on the Cu-CN-0.5 surface. Specifically, some of the π electrons in the tris-s-triazine units were transferred to the copper oxide particles along the newly formed chemical bonds (C(π)-O-Cu), forming a π-deficient area on the tris-s-triazine plane near the complexation site. In a typical Cu-CN-0.5 Fenton-like process, a stable π-π interaction was established due to the favorable positive-negative match of electrostatic potential between the aromatic pollutants and π-deficient areas, leading to a significant improvement in Cu-CN-0.5's adsorption capacity for aromatic pollutants. Furthermore, pollutants also delivered electrons to the Cu-CN-0.5 Fenton-like system via a "through-space" approach, which suppressed the futile oxidation of H2O2 in reducing the high-valent Cu2+ and significantly improved the generation efficiency of •OH with high oxidative capacity. As expected, Cu-CN-0.5 not only exhibited an efficient Fenton degradation for several typical aromatic organic pollutants, but also demonstrated both a low metal leaching rate (0.12 mg/L) and a H2O2 utilization rate exceeding 80%. The distinctive Fenton degradation mechanism substantiated the potential of the as-prepared material for effective wastewater treatment applications.

Dietary choline intake and colorectal cancer: a cross-sectional study of 2005-2018 NHANES cycles.

Background: It remains unclear if choline intake is associated with colorectal cancer. Therefore, we examined data from the National Health and Nutrition Examination Survey (NHANES). Methods: This cross-sectional study included 32,222 U.S. adults in the 2005-2018 NHANE cycles, among whom 227 reported colorectal cancer. Dietary choline was derived from 24-h recalls. Logistic regression estimated odds of colorectal cancer across increasing intake levels, adjusting for potential confounders. Results: After adjusting for sociodemographic variables, BMI, alcohol use, smoking status, comorbidities, and dietary factors (energy, fat, fiber, and cholesterol), the odds ratio (OR) for colorectal cancer was 0.86 (95% CI: 0.69-1.06, p = 0.162) per 100 mg higher choline intake. Across increasing quartiles of choline intake, a non-significant inverse trend was observed (Q4 vs. Q1 OR: 0.76, 95%CI: 0.37 ~ 1.55, P-trend = 0.23). Subgroup analyses revealed largely consistent associations, with a significant interaction by hypertension status (P-interaction =0.022). Conclusion: In this large, nationally representative sample of U.S. adults, higher dietary choline intake was not significantly associated with colorectal cancer odds after adjusting for potential confounders. However, a non-significant inverse trend was observed. Further prospective studies are needed to confirm these findings and elucidate the underlying mechanisms.

WeiNaiAn capsule attenuates intestinal mucosal injury and regulates gut microbiome in indomethacin-induced rat.

Indomethacin, as a non-steroidal anti-inflammatory drugs, is widely used in the clinic. However, it can cause severe injury to the gastrointestinal tract and the incidence is increasing. It has become an essential clinical problem in preventing intestinal damage. Teprenone has been reported to have a significant positive effect on intestinal mucosal lesions, but long-term use of teprenone can elicit adverse reactions. WeiNaiAn capsule is a traditional Chinese medicine formulation used widely in the treatment of gastric and duodenal mucosal injury. However, how WeiNaiAn protects against intestinal mucosal injury and its mechanism of action are not known. In this study, WeiNaiAn capsule or Teprenone treatment improved the intestinal mucosal pathological score and antioxidant level in indomethacin-induced rats. 16 S rRNA sequence data showed WeiNaiAn capsule reverted the structure community and replenished the beneficial bacteria. Furthermore, fingerprint analysis revealed multiple components of WeiNaiAn capsule, including calycosin glucoside, ginsenoside Rg1, ginsenoside Rb1, taurocholic acid sodium, formonetin, and calycosin glucoside. The components of WeiNaiAn capsule promoted the wound healing of the epithelial cell in vitro. Moreover, the components of WeiNaiAn capsule inhibited the protein expressions of phosphoinositide 3-kinase /protein kinase B /mammalian target of rapamycin in hydrogen peroxide or lipopolysaccharides-induced cell model. In conclusion, WeiNaiAn capsule improves intestinal mucosal injury by regulating cell migration, enhancing antioxidant activity, and promoting the structure of the bacterial community homeostasis, the multiple targets provide the parameters for the treatment in the clinic.

Fitness cost of tet(A) type I variant-mediated tigecycline resistance in Klebsiella pneumoniae.

OBJECTIVE: The aim of the present study is to explore the impact of the tet(A) type I variant (tetA-v1) on its fitness effect in Klebsiella pneumoniae. METHODS: Clinical K. pneumoniae strains were utilized as parental strains to generate strains carrying only the plasmid vector (pBBR1MCS-5) or the tetA-v1 recombinant plasmid (ptetA-v1). Antimicrobial susceptibility testing was conducted to estimate the contribution of tetA-v1 to drug resistance. Plasmid stability was evaluated by serial passage over 10 consecutive days in the absence of tigecycline. Biological fitness was examined through growth curve analysis, in vitro competition assays and a neutropenic mouse thigh infection model. RESULTS: A 2-4-fold increase in tigecycline MIC was observed following the acquisition of tetA-v1. Without tigecycline treatment, the stability of ptetA-v1 plasmids has been decreasing since day 1. The ptetA-v1 plasmid in Kp89, Kp91, and Kp93 exhibited a decrease of about 20% compared to the pBBR1MCS-5 plasmid. The acquisition of the tetA-v1 gene could inhibit the growth ability of K. pneumoniae strains both in vitro and in vivo. tetA-v1 gene imposed a fitness cost in K. pneumoniae, particularly in the CRKP strain Kp51, with a W value of approximately 0.56. CONCLUSION: The presence of tetA-v1 is associated with a significant fitness cost in K. pneumoniae in the absence of tigecycline, both in vitro and in vivo.

Extracellular perception of multiple novel core effectors from the broad host-range pear anthracnose pathogen Colletotrichum fructicola in the nonhost Nicotiana benthamiana.

Colletotrichum fructicola is emerging as a devastating pathogenic fungus causing anthracnose in a wide range of horticultural crops, particularly fruits. Exploitation of nonhost resistance (NHR) represents a robust strategy for plant disease management. Perception of core effectors from phytopathogens frequently leads to hypersensitive cell death and resistance in nonhost plants; however, such core effectors in C. fructicola and their signaling components in non-hosts remain elusive. Here, we found a virulent C. fructicola strain isolated from pear exhibits non-adaptation in the model plant Nicotiana benthamiana. Perception of secreted molecules from C. fructicola appears to be a dominant factor in NHR, and four novel core effectors-CfCE4, CfCE25, CfCE61, and CfCE66-detected by N. benthamiana were, accordingly, identified. These core effectors exhibit cell death-inducing activity in N. benthamiana and accumulate in the apoplast. With a series of CRISPR/Cas9-edited mutants or gene-silenced plants, we found the coreceptor BAK1 and helper NLRs including ADR1, NRG1, and NRCs mediate perceptions of these core effectors in N. benthamiana. Concurrently, multiple N. benthamiana genes encoding cell surface immune receptors and intracellular immune receptors were greatly induced by C. fructicola. This work represents the first characterization of the repertoire of C. fructicola core effectors responsible for NHR. Significantly, the novel core effectors and their signaling components unveiled in this study offered insights into a continuum of layered immunity during NHR and will be helpful for anthracnose disease management in diverse horticultural crops.

Risk analysis of noise-induced hearing loss of workers in the automobile manufacturing industries based on back-propagation neural network model: a cross-sectional study in Han Chinese population.

OBJECTIVES: This study aims to predict the risk of noise-induced hearing loss (NIHL) through a back-propagation neural network (BPNN) model. It provides an early, simple and accurate prediction method for NIHL. DESIGN: Population based, a cross sectional study. SETTING: Han, China. PARTICIPANTS: This study selected 3266 Han male workers from three automobile manufacturing industries. PRIMARY OUTCOME MEASURES: Information including personal life habits, occupational health test information and occupational exposure history were collected and predictive factors of NIHL were screened from these workers. BPNN and logistic regression models were constructed using these predictors. RESULTS: The input variables of BPNN model were 20, 16 and 21 important factors screened by univariate, stepwise and lasso-logistic regression. When the BPNN model was applied to the test set, it was found to have a sensitivity (TPR) of 83.33%, a specificity (TNR) of 85.92%, an accuracy (ACC) of 85.51%, a positive predictive value (PPV) of 52.85%, a negative predictive value of 96.46% and area under the receiver operating curve (AUC) is: 0.926 (95% CI: 0.891 to 0.961), which demonstrated the better overall properties than univariate-logistic regression modelling (AUC: 0.715) (95% CI: 0.652 to 0.777). The BPNN model has better predictive performance against NIHL than the stepwise-logistic and lasso-logistic regression model in terms of TPR, TNR, ACC, PPV and NPV (p<0.05); the area under the receiver operating characteristics curve of NIHL is also higher than that of the stepwise and lasso-logistic regression model (p<0.05). It was a relatively important factor in NIHL to find cumulative noise exposure, auditory system symptoms, age, listening to music or watching video with headphones, exposure to high temperature and noise exposure time in the trained BPNN model. CONCLUSIONS: The BPNN model was a valuable tool in dealing with the occupational risk prediction problem of NIHL. It can be used to predict the risk of an individual NIHL.

Adaptive regulation of miRNAs/milRNAs in tissue-specific interaction between apple and Valsa mali.

In plant-pathogen interactions, pathogens display tissue specificity, infecting and causing disease in particular tissues. However, the involvement of microRNAs/microRNA-like RNAs (miRNAs/milRNAs) in tissue-specific regulation during plant-pathogen interactions remains largely unexplored. This study investigates the differential expression of miRNAs/milRNAs, as well as their corresponding target genes, in interactions between Valsa mali (Vm) and different apple tissues. The results demonstrated that both apple miRNAs and Vm milRNAs exhibited distinct expression profiles when Vm infected bark and leaves, with functionally diverse corresponding target genes. Furthermore, one apple miRNA (Mdo-miR482a) and one Vm milRNA (Vm-milR57) were identified as exhibiting tissue-specific expression in interactions between Vm and apple bark or leaves. Mdo-miR482a was exclusively up-regulated in response to Vm infection in bark and target a nucleotide-binding leucine-rich repeat (NLR) gene of apple. When Mdo-miR482a was transiently over-expressed or silenced, the resistance was significantly reduced or improved. Similarly, transient expression of the NLR gene also showed an increase in resistance. Vm-milR57 could target two essential pathogenicity-related genes of Vm. During Vm infection in bark, the expression of Vm-milR57 was down-regulated to enhance the expression of the corresponding target gene to improve the pathogenicity. The study is the first to reveal tissue-specific characteristics of apple miRNAs and Vm milRNAs in interactions between Vm and different apple tissues, providing new insights into adaptive regulation in tissue-specific interactions between plants and fungi.

Identification and genetic validation of leukemia inhibitory factor super-enhancers in acute respiratory distress syndrome and lung cancer.

Super-enhancers play prominent roles in driving robust pathological gene expression, but they are hidden in human genome at noncoding regions, making them difficult to explore. Leukemia inhibitory factor (LIF) is a multifunctional cytokine crucially involved in acute respiratory distress syndrome (ARDS) and lung cancer progression. However, the mechanisms governing LIF regulation in disease contexts remain largely unexplored. In this study, we observed elevated levels of LIF in the bronchoalveolar lavage fluid (BALF) of patients with sepsis-related ARDS compared to those with nonsepsis-related ARDS. Furthermore, both basal and LPS-induced LIF expression were under the control of super-enhancers. Through analysis of H3K27Ac ChIP-seq data, we pinpointed three potential super-enhancers (LIF-SE1, LIF-SE2, and LIF-SE3) located proximal to the LIF gene in cells. Notably, genetic deletion of any of these three super-enhancers using CRISPR-Cas9 technology led to a significant reduction in LIF expression. Moreover, in cells lacking these super-enhancers, both cell growth and invasion capabilities were substantially impaired. Our findings highlight the critical role of three specific super-enhancers in regulating LIF expression and offer new insights into the transcriptional regulation of LIF in ARDS and lung cancer.