ABSTRACT
The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.
Subject(s)
Chitin , Flowers , Hypocreales , Oryza , Plant Diseases , Oryza/microbiology , Oryza/metabolism , Oryza/genetics , Plant Diseases/microbiology , Chitin/metabolism , Flowers/microbiology , Hypocreales/pathogenicity , Hypocreales/genetics , Hypocreales/metabolism , Signal Transduction , Host-Pathogen Interactions , Plant Proteins/metabolism , Plant Proteins/genetics , Virulence , Virulence Factors/metabolism , Virulence Factors/genetics , Fungal Proteins/metabolism , Fungal Proteins/geneticsABSTRACT
Plant disease, a huge burden, can cause yield loss of up to 100% and thus reduce food security. Actually, smart diagnosing diseases with plant phenomics is crucial for recovering the most yield loss, which usually requires sufficient image information. Hence, phenomics is being pursued as an independent discipline to enable the development of high-throughput phenotyping for plant disease. However, we often face challenges in sharing large-scale image data due to incompatibilities in formats and descriptions provided by different communities, limiting multidisciplinary research exploration. To this end, we build a Plant Phenomics Analysis of Disease (PlantPAD) platform with large-scale information on disease. Our platform contains 421 314 images, 63 crops and 310 diseases. Compared to other databases, PlantPAD has extensive, well-annotated image data and in-depth disease information, and offers pre-trained deep-learning models for accurate plant disease diagnosis. PlantPAD supports various valuable applications across multiple disciplines, including intelligent disease diagnosis, disease education and efficient disease detection and control. Through three applications of PlantPAD, we show the easy-to-use and convenient functions. PlantPAD is mainly oriented towards biologists, computer scientists, plant pathologists, farm managers and pesticide scientists, which may easily explore multidisciplinary research to fight against plant diseases. PlantPAD is freely available at http://plantpad.samlab.cn.
Subject(s)
Phenomics , Plant Diseases , Crops, Agricultural , Image Processing, Computer-Assisted , PhenotypeABSTRACT
Phytophthora effector PSR1 suppresses small RNA (sRNA)-mediated immunity in plants, but the underlying mechanism remains unknown. Here, we show that Phytophthora suppressor of RNA silencing 1 (PSR1) contributes to the pathogenicity of Phytophthora sojae and specifically binds to three conserved C-terminal domains of the eukaryotic PSR1-Interacting Protein 1 (PINP1). PINP1 encodes PRP16, a core pre-mRNA splicing factor that unwinds RNA duplexes and binds to primary microRNA transcripts and general RNAs. Intriguingly, PSR1 decreased both RNA helicase and RNA-binding activity of PINP1, thereby dampening sRNA biogenesis and RNA metabolism. The PSR1-PINP1 interaction caused global changes in alternative splicing (AS). A total of 5,135 genes simultaneously exhibited mis-splicing in both PSR1-overexpressing and PINP1-silenced plants. AS upregulated many mRNA transcripts that had their introns retained. The high occurrence of intron retention in AS-induced transcripts significantly promoted Phytophthora pathogen infection in Nicotiana benthamiana, and this might be caused by the production of truncated proteins. Taken together, our findings reveal a key role for PINP1 in regulating sRNA biogenesis and plant immunity.
Subject(s)
Phytophthora , RNA, Small Untranslated , Plant Diseases , Plant Immunity , Plants , RNA Precursors , Glycine maxABSTRACT
Flexible membranes with ultrathin thickness and excellent mechanical properties have shown great potential for broad uses in solid polymer electrolytes (SPEs), on-skin electronics, etc. However, an ultrathin membrane (<5 µm) is rarely reported in the above applications due to the inherent trade-off between thickness and antifailure ability. We discover a protic solvent penetration strategy to prepare ultrathin, ultrastrong layered films through a continuous interweaving of aramid nanofibers (ANFs) with the assistance of simultaneous protonation and penetration of a protic solvent. The thickness of a pure ANF film can be controlled below 5 µm, with a tensile strength of 556.6 MPa, allowing us to produce the thinnest SPE (3.4 µm). The resultant SPEs enable Li-S batteries to cycle over a thousand times at a high rate of 1C due to the small ionic impedance conferred by the ultrathin characteristic and regulated ionic transportation. Besides, a high loading of the sulfur cathode (4 mg cm-2) with good sulfur utilization was achieved at a mild temperature (35 °C), which is difficult to realize in previously reported solid-state Li-S batteries. Through a simple laminating process at the wet state, the thicker film (tens of micrometers) obtained exhibits mechanical properties comparable to those of thin films and possesses the capability to withstand high-velocity projectile impacts, indicating that our technique features a high degree of thickness controllability. We believe that it can serve as a valuable tool to assemble nanomaterials into ultrathin, ultrastrong membranes for various applications.
ABSTRACT
Age-related tau astrogliopathy (ARTAG) is detectable in the brains of over one-third of autopsied persons beyond age 80, but the pathoetiology of ARTAG is poorly understood. Insights can be gained by analyzing risk factors and comorbid pathologies. Here we addressed the question of which prevalent co-pathologies are observed with increased frequency in brains with ARTAG. The study sample was the National Alzheimer's Coordinating Center (NACC) data set, derived from multiple Alzheimer's disease research centers (ADRCs) in the United States. Data from persons with unusual conditions (e.g. frontotemporal dementia) were excluded leaving 504 individual autopsied research participants, clustering from 20 different ADRCs, autopsied since 2020; ARTAG was reported in 222 (44.0%) of included participants. As has been shown previously, ARTAG was increasingly frequent with older age and in males. The presence and severity of other common subtypes of pathology that were previously linked to dementia were analyzed, stratifying for the presence of ARTAG. In logistical regression-based statistical models that included age and sex as covariates, ARTAG was relatively more likely to be found in brains with limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and in brains with comorbid cerebrovascular pathology (arteriolosclerosis and/or brain infarcts). However, ARTAG was not associated with severe Alzheimer's disease neuropathologic change (ADNC), or primary age-related tauopathy (PART). In a subset analysis of 167 participants with neurocognitive testing data, there was a marginal trend for ARTAG pathology to be associated with cognitive impairment as assessed with MMSE scores (P = 0.07, adjusting for age, sex, interval between final clinic visit and death, and ADNC severity). A limitation of the study was that there were missing data about ARTAG pathologies, with incomplete operationalization of ARTAG according to anatomic region and pathologic subtypes (e.g., thorn-shaped or granular-fuzzy astrocytes). In summary, ARTAG was not associated with ADNC, whereas prior observations about ARTAG occurring with increased frequency in aging, males, and brains with LATE-NC were replicated. It remains to be determined whether the increased frequency of ARTAG in brains with comorbid cerebrovascular pathology is related to local infarctions or neuroinflammatory signaling, or with some other set of correlated factors including blood-brain barrier dysfunction.
Subject(s)
Alzheimer Disease , Dementia , TDP-43 Proteinopathies , Male , Humans , Aged, 80 and over , Alzheimer Disease/pathology , tau Proteins/metabolism , Aging/pathology , Brain/metabolismABSTRACT
BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.
ABSTRACT
Influenza (flu) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit similar clinical symptoms, complicating the diagnosis and clinical management of these critical respiratory infections. Thus, there is an urgent need for rapid on-site detection technologies that can simultaneously detect SARS-CoV-2 and influenza A viruses. Here, we have developed the first platform that combines in situ sampling with immune swabs and multichannel surface-enhanced Raman spectroscopy (SERS) for simultaneous screening of these two respiratory viruses in a single assay. A seed-mediated growth method was used to assemble a number of silver spheres on the surface of Fe3O4@SiO2 spheres, which not only creates extensive Raman hotspots but also provides numerous sites for Raman signaling molecules, enhancing the sensing sensitivity. Integrating two specific Raman signaling molecules into the nanospheres allows for the parallel detection of both viruses, improving the efficiency of SERS signal read-out. Rapid quantitative screening of both SARS-CoV-2 and H1N1 is achievable within 15 min, with detection limits of 7.76, and 8.13 pg·mL-1 for their respective target proteins. The platform demonstrated excellent performance in testing and analyzing 98 clinical samples (SARS-CoV-2:50; influenza A:48), achieving sensitivities of 88.00, and 95.83% for SARS-CoV-2 and influenza A, respectively. Pearson's correlation analysis revealed a significant correlation with the clinical CT values (P < 0.0001), underscoring the great potential of this platform for the early, rapid, and simultaneous diagnostic discrimination of multiple pathogens.
Subject(s)
COVID-19 , Influenza A virus , SARS-CoV-2 , Silver , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , SARS-CoV-2/isolation & purification , Humans , COVID-19/diagnosis , COVID-19/virology , Silver/chemistry , Influenza A virus/isolation & purification , Silicon Dioxide/chemistry , Influenza, Human/diagnosis , Influenza, Human/virology , Metal Nanoparticles/chemistryABSTRACT
The conventional lateral flow immunoassay (LFIA) method using colloidal gold nanoparticles (Au NPs) as labeling agents faces two inherent limitations, including restricted sensitivity and poor quantitative capability, which impede early viral infection detection. Herein, we designed and synthesized CsPbBr3 perovskite quantum dot-based composite nanoparticles, CsPbBr3@SiO2@Fe3O4 (CSF), which integrated fluorescence detection and magnetic enrichment properties into LFIA technology and achieved rapid, sensitive, and convenient quantitative detection of the SARS-CoV-2 virus N protein. In this study, CsPbBr3 served as a high-quantum-yield fluorescent signaling probe, while SiO2 significantly enhanced the stability and biomodifiability of CsPbBr3. Importantly, the SiO2 shell shows relatively low absorption or scattering toward fluorescence, maintaining a quantum yield of up to 74.4% in CsPbBr3@SiO2. Assembly of Fe3O4 nanoparticles mediated by PEI further enhanced the method's sensitivity and reduced matrix interference through magnetic enrichment. Consequently, the method achieved a fluorescent detection range of 1 × 102 to 5 × 106 pg·mL-1 after magnetic enrichment, with a limit of detection (LOD) of 58.8 pg·mL-1, representing a 13.3-fold improvement compared to nonenriched samples (7.58 × 102 pg·mL-1) and a 2-orders-of-magnitude improvement over commercial colloidal gold kits. Furthermore, the method exhibited 80% positive and 100% negative detection rates in clinical samples. This approach holds promise for on-site diagnosis, home-based quantitative tests, and disease procession evaluation.
Subject(s)
Metal Nanoparticles , Silicon Dioxide , Gold , Fluorescent Dyes , Immunoassay/methods , Gold ColloidABSTRACT
Tectorigenin (TEC) as a plant extract has the advantage of low side effects on metabolic dysfunction-associated steatohepatitis (MASH) treatment. Our previous study have shown that tRNA-derived RNA fragments (tRFs) associated with autophagy and pyroptosis in MASH, but whether TEC can mitigate MASH through tRFs-mediated mitophagy is not fully understood. This study aims to investigate whether TEC relies on tRFs to adjust the crosstalk of hepatocyte mitophagy with pyroptosis in MASH. Immunofluorescence results of PINK1 and PRKN with MitoTracker Green-labeled mitochondria verified that TEC enhanced mitophagy. Additionally, TEC inhibited pyroptosis, as reflected by the level of GSDME, NLRP3, IL-1ß, and IL-18 decreased after TEC treatment, while the effect of pyroptosis inhibition by TEC was abrogated by Pink1 silencing. We found that the upregulation expression of tRF-3040b caused by MASH was suppressed by TEC. The promotion of mitophagy and the suppression of pyroptosis induced by TEC were abrogated by tRF-3040b mimics. TEC reduced lipid deposition, inflammation, and pyroptosis, and promoted mitophagy in mice, but tRF-3040b agomir inhibited these effects. In summary, our findings provided that TEC significantly reduced the expression of tRF-3040b to enhance mitophagy, thereby inhibiting pyroptosis in MASH. We elucidated a powerful theoretical basis and provided safe and effective potential drugs for MASH with the prevention and treatment.
Subject(s)
Down-Regulation , Isoflavones , Mice, Inbred C57BL , Mitophagy , Pyroptosis , Pyroptosis/drug effects , Mitophagy/drug effects , Animals , Mice , Male , Isoflavones/pharmacology , Down-Regulation/drug effects , Fatty Liver/metabolism , Fatty Liver/pathology , Fatty Liver/drug therapy , Fatty Liver/genetics , HumansABSTRACT
Photocathodes play a crucial role in photoelectronic imaging and vacuum electronic devices. The quantum efficiency of photocathodes, which determines their performance, can be enhanced through materials engineering. However, the quantum efficiency of conventional planar photocathodes remains consistently low, at around 25%. In this paper, we propose what we believe is a novel structure of AlGaN nanowire array to address this issue. We investigate the photoemission characteristics of the nanowire array using the "four-step" process, which takes into account optical absorption, electron transportation, electron emission, and electron collection. We compare the quantum efficiency of nanowire arrays with different structure sizes and Al components. After studying the effect of incident light at various angles on the nanowire array photocathode, we identify the optimal dimensional parameters: a height of 400â¼500 nm and a wire width of 200â¼300 nm. Furthermore, we improved the collection efficiency of the photocathode by introducing a built-in/external electric field, and obtained a 104.4% enhancement of the collection current with the built-in electric field, meanwhile the photocurrent was increased by 87% compared to the case without the external electric field. These findings demonstrate the potential of optimizing photocathode performance through the development of a novel model and adjustment of parameters, offering a promising approach for photocathode applications.
ABSTRACT
BACKGROUND: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. METHODS: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. RESULTS: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC. CONCLUSION: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Angiopathies , Diet, Mediterranean , Intra-Abdominal Fat , Prediabetic State , Protective Factors , Risk Reduction Behavior , Humans , Prediabetic State/epidemiology , Prediabetic State/diagnosis , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Male , Female , Middle Aged , Intra-Abdominal Fat/physiopathology , Aged , Risk Factors , Risk Assessment , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/prevention & control , Time Factors , Incidence , Adiposity , United Kingdom/epidemiology , Adult , Diet, Healthy , Exercise , Healthy Lifestyle , Obesity, Abdominal/diagnosis , Obesity, Abdominal/epidemiology , Obesity, Abdominal/physiopathology , Prospective StudiesABSTRACT
BACKGROUND: The FDA issued a "black box" warning regarding risks of fluoroquinolones in 2008 with updates in 2011, 2013, and 2016. OBJECTIVE: To examine antimicrobial use in hospital-treated UTIs from 2000 to 2020. DESIGN: Cross-sectional study with interrupted time series analysis. PARTICIPANTS: Patient encounters with a diagnosis of UTI from January 2000 to March 2020, excluding diagnoses of renal abscess, chronic cystitis, and infection of the gastrointestinal tract, lungs, or prostate. MAIN MEASURES: Monthly use of fluoroquinolone and non-fluoroquinolone antibiotics were assessed. Fluoroquinolone resistance was assessed in available cultures. Interrupted time series analysis examined level and trend changes of antimicrobial use with each FDA label change. KEY RESULTS: A total of 9,950,790 patient encounters were included. From July 2008 to March 2020, fluoroquinolone use declined from 61.7% to 11.7%, with similar negative trends observed in inpatients and outpatients, age ≥ 60 and < 60 years, males and females, patients with and without pyelonephritis, and across physician specialties. Ceftriaxone use increased from 26.4% encounters in July 2008 to 63.6% of encounters in March 2020. Among encounters with available culture data, fluoroquinolone resistance declined by 28.9% from 2009 to 2020. On interrupted time series analysis, the July 2008 FDA warning was associated with a trend change (-0.32%, < 0.001) and level change (-5.02%, p < 0.001) in monthly fluoroquinolone use. CONCLUSIONS: During this era of "black box" warnings, there was a decline in fluoroquinolone use for hospital-treated UTI with a concomitant decline in fluoroquinolone resistance and rise in ceftriaxone use. Efforts to restrict use of a medication class may lead to compensatory increases in use of a single alternative agent with changes in antimicrobial resistance profiles.
Subject(s)
Anti-Bacterial Agents , United States Food and Drug Administration , Urinary Tract Infections , Humans , Urinary Tract Infections/drug therapy , Male , Female , United States/epidemiology , Cross-Sectional Studies , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Middle Aged , Aged , Adult , Fluoroquinolones/therapeutic use , Interrupted Time Series Analysis , Cross Infection/drug therapy , Cross Infection/epidemiologyABSTRACT
BACKGROUND: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. METHODS: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. CONCLUSIONS: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.
Subject(s)
Anti-Mullerian Hormone , Birth Rate , Cryopreservation , Embryo Transfer , Live Birth , Humans , Female , Embryo Transfer/methods , Embryo Transfer/statistics & numerical data , Embryo Transfer/trends , Pregnancy , Adult , Retrospective Studies , Prognosis , Anti-Mullerian Hormone/blood , Live Birth/epidemiology , Pregnancy Rate , Ovarian Reserve/physiology , Age Factors , Fertilization in Vitro/methods , Pregnancy Outcome/epidemiologyABSTRACT
Chronic alcohol consumption is a major risk factor for alcoholic steatohepatitis (ASH). Previous studies have shown that direct injury of hepatocytes is the key factor in its occurrence and development. However, our study shows that the role of Kupffer cells in ASH cannot be ignored. We isolated Kupffer cells from the livers of ASH mice and found that alcohol consumption induced Kupffer cell pyroptosis and increased the release of interleukin-1ß (IL-1ß). Furthermore, we screened the related m6A enzyme methyltransferase-like 3 (METTL3) from liver Kupffer cells, and found that silencing METTL3 alleviated inflammatory cytokine eruption by Kupffer cell pyroptosis in ASH mice. In vitro, we silenced METTL3 with lentivirus in BMDMs and RAW264.7 cells and confirmed that METTL3 could reduce pyroptosis by influencing the splicing of pri-miR-34A. Together, our results revealed a critical role of KC pyroptosis in ASH and highlighted the mechanism by which METLL3 relieves cell pyroptosis, which could be a promising therapeutic strategy for ASH.
Subject(s)
Fatty Liver, Alcoholic , MicroRNAs , Animals , Mice , Kupffer Cells , Pyroptosis , Hepatocytes , MethyltransferasesABSTRACT
AIMS: To construct an efficient bacterial complex to degrade nicosulfuron and clarify its degradative characteristics, promote the growth of maize (Zea mays), and provide a theoretical foundation for the efficient remediation of soil contaminated with nicosulfuron. METHODS AND RESULTS: Biocompatibility was determined by the filter paper sheet method by mixing Serratia marcescens A1 and Bacillus cereus A2 in a 1:1 ratio, yielding A12. The optimum culture conditions for the bacterial composite were obtained based on a three-factor, three-level analysis using response surface methodology, with 29.25 g l-1 for maltodextrin, 10.04 g l-1 for yeast extract, and 19.93 g l-1 for NaCl, which resulted in 92.42% degradation at 4 d. The degradation characteristics of A12 were clarified as follows: temperature 30°C, pH 7, initial concentration of nicosulfuron 20 mg l-1, and 4% inoculum. The ability to promote growth was determined by measuring the ratio of the lysosphere diameter (D) to the colony diameter (d), and the ability of the complex A12 to promote growth was higher than that of the two single strains. CONCLUSIONS: Nicosulfuron degradation in sterilized and unsterilized soils reached 85.4% and 91.2% within 28 d, respectively. The ability of the strains to colonize the soil was determined by extraction of total soil DNA, primer design, and gel electrophoresis. The bioremediation effect of A12 was confirmed by the maximum recovery of fresh weight (124.35%) of nicosulfuron-sensitive crop plants and the significant recovery of soil enzyme activities, as measured by the physiological indices in the sensitive plants.
Subject(s)
Bacillus cereus , Biodegradation, Environmental , Pyridines , Soil Microbiology , Soil Pollutants , Sulfonylurea Compounds , Sulfonylurea Compounds/metabolism , Soil Pollutants/metabolism , Pyridines/metabolism , Bacillus cereus/metabolism , Bacillus cereus/growth & development , Serratia marcescens/metabolism , Serratia marcescens/growth & development , Zea mays/metabolism , Zea mays/microbiology , Soil/chemistry , Herbicides/metabolismABSTRACT
Soil contains a substantial amount of organic carbon, and its feedback to global warming has garnered widespread attention due to its potential to modulate atmospheric carbon (C) storage. Temperature sensitivity (Q10) has been widely utilized as a measure of the temperature-induced enhancement in soil organic carbon (SOC) decomposition. It is currently rare to incorporate Q10 of CO2 and CH4 into the study of waterlogged soil profiles and explore the possibility of artificially reducing Q10 in rice fields. To investigate the key drivers of Q10, we collected 0-1 m paddy soil profiles, and stratified the soil for submerged anaerobic incubation. The relationship between SOC availability, microbial activity, and the Q10 of CO2 and CH4 emissions was examined. Our findings indicate that as the soil layer deepens, soil C availability and microbial activity declined, and the Q10 of anaerobic degradation increased. Warming increased C availability and microbial activity, accompanied by weakened temperature sensitivity. The Q10 of CO2 correlated strongly with soil resistant C components, while the Q10 of CH4 was significantly influenced by labile substrates. The temperature sensitivity of CH4 (Q10 = 3.99) was higher than CO2 emissions (Q10 = 1.78), indicating the need for greater attention of CH4 in predicting warming's impact on anaerobic degradation in rice fields. Comprehensively assessing CO2 and CH4 emissions, the 20-40 cm subsurface soil is the most temperature-sensitive. Despite being a high-risk area for C loss and CH4 emissions, management of this soil layer in agriculture has the potential to reduce the threat of global warming. This study underscores the importance of subsurface soil in paddy fields, advocating greater attention in scientific simulations and predictions of climate change.
Subject(s)
Carbon , Methane , Oryza , Soil Microbiology , Soil , Temperature , Soil/chemistry , Carbon/analysis , Carbon/metabolism , Oryza/growth & development , Methane/analysis , Methane/metabolism , Anaerobiosis , Carbon Dioxide/analysis , Carbon Dioxide/metabolism , Global WarmingABSTRACT
As a major challenge to global food security, soil salinity is an important abiotic stress factor that seriously affects the crop growth and yield. In this study, the mechanism of salt resistance of Pantoea jilinensis D25 and its improving effect on salt tolerance of tomato were explored with salt resistance-related genes identified in strain D25 by genomic sequencing. The results showed that in comparison with the treatment of NaCl, strain D25 significantly increased the fresh weight, shoot length, root length, and chlorophyll content of tomato under salt stress by 46.7%, 20%, 42.4%, and 44.2%, respectively, with increased absorptions of various macronutrients and micronutrients and decreased accumulation of Na+. The activities of defense enzymes (peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, and polyphenol oxidase) were enhanced, while the content of malondialdehyde was decreased. The results of quantitative real-time PCR analysis showed that the expressions of genes (SlSOS1, SlNHX1, SlHKT1.1, SlSOD1, SlAPX2, SlAOS, SlPin II, Solyc08g066270.1, Solyc03g083420.2 and SlGA20ox1) related to ion transporters, antioxidant machinery, key defense, serine/threonine protein kinase synthesis, and gibberellin (GA) signal protein were up-regulated and were the highest in the treatment of both NaCl and strain D25. The activities of enzymes (dehydrogenase, urease, invertase, and catalase activities) related to soil fertility were enhanced. The results of 16S rRNA sequencing showed that soil microbial diversity and the abundance of probiotics (e.g., Acidibacter, Limnobacter, and Romboutsia) were significantly increased. Our study provided strong experimental evidence to support the agricultural application of strain D25 in the promotion of growth in crops.
Subject(s)
Pantoea , Solanum lycopersicum , Antioxidants/metabolism , Catalase , Salt Tolerance , Pantoea/metabolism , Soil/chemistry , RNA, Ribosomal, 16S/genetics , Sodium ChlorideABSTRACT
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions with excessive inflammation in the lung. Glucocorticoids had been widely used for ALI/ARDS, but their clinical benefit remains unclear. Here, we tackled the problem by conjugating prednisolone (PSL) with a targeting peptide termed CRV. Systemically administered CRV selectively homes to the inflamed lung of a murine ALI model, but not healthy organs or the lung of healthy mice. The expression of the CRV receptor, retinoid X receptor ß, was elevated in the lung of ALI mice and patients with interstitial lung diseases, which may be the basis of CRV targeting. We then covalently conjugated PSL and CRV with a reactive oxygen species (ROS)-responsive linker in the middle. While being intact in blood, the ROS linker was cleaved intracellularly to release PSL for action. In vitro, CRV-PSL showed an anti-inflammatory effect similar to that of PSL. In vivo, CRV conjugation increased the amount of PSL in the inflamed lung but reduced its accumulation in healthy organs. Accordingly, CRV-PSL significantly reduced lung injury and immune-related side effects elsewhere. Taken together, our peptide-based strategy for targeted delivery of glucocorticoids for ALI may have great potential for clinical translation.
Subject(s)
Acute Lung Injury , Respiratory Distress Syndrome , Mice , Animals , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Pharmaceutical Preparations/metabolism , Reactive Oxygen Species/metabolism , Acute Lung Injury/drug therapy , Peptides/metabolism , Lung/metabolism , Respiratory Distress Syndrome/drug therapy , Prednisolone/therapeutic use , Lipopolysaccharides/pharmacologyABSTRACT
The aging phenomenon is commonly observed in quantum-dot light emitting diodes (QLEDs), involving complex chemical or physical processes. Resolving the underlying mechanism of these aging issues is crucial to deliver reliable electroluminescent devices in future display applications. Here, we report a reversible positive aging phenomenon that the device brightness and efficiency significantly improve after device operation, but recover to initial states after long-time storage or mild heat treatment, which can be termed as warming-up effects. Steady and transient equivalent circuit analysis suggest that the radiative recombination current dramatically increases but electron leakage from the quantum dots (QDs) to hole transport layer becomes more accessible during the warming-up process. Further analysis discloses that the notable enhancement of device efficiency can be ascribed to the filling of shell traps in gradient alloyed QDs. This work reveals a distinct positive aging phenomenon featured with reversibility, and further guidelines would be provided to achieve stable QLED devices in real display applications.