Association of healthy diet score and adiposity with risk of colorectal cancer: findings from the UK Biobank prospective cohort study.

PURPOSE: To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. METHODS: The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. RESULTS: Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. CONCLUSION: Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk.

Human neural stem cell secretome relieves endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after traumatic brain injury in a rat model.

Neural stem cell secretome (NSC-S) plays an important role in neuroprotection and recovery. Studies have shown that endoplasmic reticulum stress (ER stress) is involved in the progression of traumatic brain injury (TBI) and is a crucial cause of secondary damage and neuronal death after brain injury. Whether NSC-S is engaged in ER stress and ER stress-mediated neuronal apoptosis post-TBI has not been investigated. In the study, the Feeney SD male rat model was established. The results showed that NSC-S treatment significantly improved the behavior of rats with TBI. In addition, NSC-S relieved ER stress in TBI rats and was observed by transmission electron microscopy and western blot. The specific mechanism was further elucidated that restoration was achieved by alleviating the PERK-eIF2α pathway and thus protecting neurons from apoptosis. Notably, the discovery of calumenin (CALU) in NSC-S by liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) may be related to the protective effect of NSC-S on ER stress in neurons. Also, the mechanism by which it functions may be related to ubiquitination. In summary, NSC-S improved prognosis and ER stress in TBI rats and might be a promising treatment for relieving TBI.

Effects of 24-hour urine-output trajectories on the risk of acute kidney injury in critically ill patients with cirrhosis: a retrospective cohort analysis.

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications for critically ill patients with cirrhosis, but it has remained unclear whether urine output fluctuations are associated with the risk of AKI in such patients. Thus, we explored the influence of 24-h urine-output trajectory on AKI in patients with cirrhosis through latent category trajectory modeling. MATERIALS AND METHODS: This retrospective cohort study examined patients with cirrhosis using the MIMIC-IV database. Changes in the trajectories of urine output within 24 h after admission to the intensive care unit (ICU) were categorized using latent category trajectory modeling. The outcome examined was the occurrence of AKI during ICU hospitalization. The risk of AKI in patients with different trajectory classes was explored using the cumulative incidence function (CIF) and the Fine-Gray model with the sub-distribution hazard ratio (SHR) and the 95% confidence interval (CI) as size effects. RESULTS: The study included 3,562 critically ill patients with cirrhosis, of which 2,467 (69.26%) developed AKI during ICU hospitalization. The 24-h urine-output trajectories were split into five classes (Classes 1-5). The CIF curves demonstrated that patients with continuously low urine output (Class 2), a rapid decline in urine output after initially high levels (Class 3), and urine output that decreased slowly and then stabilized at a lower level (Class 4) were at higher risk for AKI than those with consistently moderate urine output (Class 1). After fully adjusting for various confounders, Classes 2, 3, and 4 were associated with a higher risk of AKI compared with Class 1, and the respective SHRs (95% CIs) were 2.56 (1.87-3.51), 1.86 (1.34-2.59), and 1.83 1.29-2.59). CONCLUSIONS: The 24-h urine-output trajectory is significantly associated with the risk of AKI in critically ill patients with cirrhosis. More attention should be paid to the dynamic nature of urine-output changes over time, which may help guide early intervention and improve patients' prognoses.

Application of dsRNA for Fungi Disease Management Sclerotinia sclerotiorum and Botrytis cinerea.

Sclerotinia sclerotiorum and Botrytis cinerea are two closely related necrotrophic plant pathogenic fungi that have garnered significant attention due to their broad host range and persistent environmental presence. The use of double-stranded RNA (dsRNA) to inhibit specific genes has demonstrated promising potential in disease management. Various RNA interference (RNAi) strategies have been developed and applied in disease management, including the use of dsRNA to silence specific genes, as well as other RNA-based approaches. These strategies show promise in controlling fungal diseases and have the potential for broader application in plant protection. Here, we present a protocol that outlines techniques for preparing dsRNA and spraying it directly to control fungal diseases. This protocol offers a practical and effective solution for managing plant diseases and has the potential to be widely applied in disease management.

Long small RNA76113 targets CYCLIC NUCLEOTIDE-GATED ION CHANNEL 5 to repress disease resistance in rice.

Small RNAs are widely involved in plant immune responses. However, the role of long small RNAs (25 to 40 nt) in monocot plant disease resistance is largely unknown. Here, we identified a long small RNA (lsiR76113) from rice (Oryza sativa) that is downregulated by Magnaporthe oryzae infection and targets a gene encoding CYCLIC NUCLEOTIDE-GATED CHANNEL 5 (CNGC5). The cngc5 mutant lines were more susceptible to M. oryzae than the wild type, while knocking down lsiR76113 in transgenic rice plants promoted pathogen resistance. A protoplast transient expression assay showed that OsCNGC5 promotes Ca2+ influx. These results demonstrate that OsCNGC5 enhances rice resistance to rice blast by increasing the cytosolic Ca2+ concentration. Importantly, exogenous Ca2+ application enhanced rice M. oryzae resistance by affecting reactive oxygen species (ROS) production. Moreover, cngc5 mutants attenuated the PAMP-triggered immunity response, including chitin-induced and flg22-induced ROS bursts and protein phosphorylation in the mitogen-activated protein kinase cascade, indicating that OsCNGC5 is essential for PAMP-induced calcium signaling in rice. Taken together, these results suggest that lsiR76113-mediated regulation of Ca2+ influx is important for PTI responses and disease resistance in rice.

Mortality patterns of patients with tonsillar squamous cell carcinoma: a population-based study.

Objective: Tonsillar squamous cell carcinoma (TSCC) and second primary malignancies (SPMs) are the most common causes of mortality in patients with primary TSCC. However, the competing data on TSCC-specific death (TSD) or SPM-related death in patients with TSCC have not been evaluated. This study aimed to analyze the mortality patterns and formulate prediction models of mortality risk caused by TSCC and SPMs. Methods: Data on patients with a first diagnosis of TSCC were extracted as the training cohort from the 18 registries comprising the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk approach of cumulation incidence function was used to estimate cumulative incidence curves. Fine and gray proportional sub-distributed hazard model analyses were performed to investigate the risk factors of TSD and SPMs. A nomogram was developed to predict the 5- and 10-year risk probabilities of death caused by TSCC and SPMs. Moreover, data from the 22 registries of the SEER database were also extracted to validate the nomograms. Results: In the training cohort, we identified 14,530 patients with primary TSCC, with TSCC (46.84%) as the leading cause of death, followed by SPMs (26.86%) among all causes of death. In the proportion of SPMs, the lungs and bronchus (22.64%) were the most common sites for SPM-related deaths, followed by the larynx (9.99%), esophagus (8.46%), and Non-Melanoma skin (6.82%). Multivariate competing risk model showed that age, ethnicity, marital status, primary site, summary stage, radiotherapy, and surgery were independently associated with mortality caused by TSCC and SPMs. Such risk factors were selected to formulate prognostic nomograms. The nomograms showed preferable discrimination and calibration in both the training and validation cohorts. Conclusion: Patients with primary TSCC have a high mortality risk of SPMs, and the competing risk nomogram has an ideal performance for predicting TSD and SPMs-related mortality. Routine follow-up care for TSCC survivors should be expanded to monitor SPMs.

Thiamine administration may increase survival benefit in critically ill patients with myocardial infarction.

Background: Myocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients. Methods: The Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out. Results: This study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results. Conclusion: Thiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.

Small RNAs contribute to citrus Huanglongbing tolerance by manipulating methyl salicylate signaling and exogenous methyl salicylate primes citrus groves from emerging infection.

Citrus production is severely threatened by the devastating Huanglongbing (HLB) disease globally. By studying and analyzing the defensive behaviors of an HLB-tolerant citrus cultivar 'Shatangju', we discovered that citrus can sense Candidatus Liberibacter asiaticus (CLas) infection and induce immune responses against HLB, which can be further strengthened by both endogenously produced and exogenously applied methyl salicylate (MeSA). This immune circuit is turned on by an miR2977-SAMT (encoding a citrus Salicylate [SA] O-methyltransferase) cascade, by which CLas infection leads to more in planta MeSA production and aerial emission. We provided both transgenic and multi-year trail evidences that MeSA is an effective community immune signal. Ambient MeSA accumulation and foliage application can effectively induce defense gene expression and significantly boost citrus performance. We also found that miRNAs are battle fields between citrus and CLas, and about 30% of the differential gene expression upon CLas infection are regulated by miRNAs. Furthermore, CLas hijacks host key processes by manipulating key citrus miRNAs, and citrus employs miRNAs that coordinately regulate defense-related genes. Based on our results, we proposed that miRNAs and associated components are key targets for engineering or breeding resistant citrus varieties. We anticipate that MeSA-based management, either induced expression or external application, would be a promising tool for HLB control.

Secular trend in disease burden of leukemia and its subtypes in China from 1990 to 2019 and its projection in 25 years.

Leukemia and its subtypes impose a major public health challenge in China. Identifying the secular trend of leukemia burden is critical to facilitate optimal healthcare planning and improve the management of leukemia. The incidence rates of leukemia from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database according to the following: subtype (acute lymphocytic leukemia [ALL], acute myeloid leukemia [AML], chronic lymphocytic leukemia [CLL], chronic myelogenous leukemia [CML], and other leukemia subtypes), sex, and age group. The average annual percentage changes and relative risks were calculated using joinpoint regression and the age-period-cohort model, respectively. The Bayesian age-period-cohort model was also applied to predict the future trend of the incidence of leukemia and its subtypes in the next 25 years. From 1990 to 2019, the age-standardized incidence rates (ASIRs) of leukemia slightly declined in males and females, which is similar to the trend of other leukemia subtypes. However, the four major leukemia subtypes, namely, ALL, AML, CLL, and CML, have been on the rise over the past three decades. The incidence rates of leukemia in children and the elderly were considerably higher than those in other age groups in males and females. Age effects were the most influential risk factor for leukemia incidence. Period effects showed that the risks of leukemia and its subtypes incidence increased with time. For cohort effects, the risks of leukemia and its subtypes were higher among the early-born cohorts compared with the late-born cohorts. The ASIRs of leukemia and its subtypes will continue to increase in the next 25 years. The burden of leukemia and its subtypes is expected to continue to increase in the next 25 years in males and females. A comprehensive understanding of the risk characteristics and disease pattern of leukemia and its subtypes is needed to formulate timely and effective intervention measures to reduce the leukemia burden in China.

Trend and projection of larynx cancer incidence and mortality in China from 1990 to 2044: A Bayesian age-period-cohort modeling study.

BACKGROUND: Larynx cancer is one of the most common cancers in head and neck, and imposes heavy burden on individual and societies. A comprehensive understanding of the burden of larynx cancer is necessary to improve prevention and control strategies. However, the secular trend of larynx cancer incidence and mortality in China remains unclear. METHODS: The incidence and deaths rates of larynx cancer from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database. The temporal trend of larynx cancer was analyzed using a joinpoint regression model. The age-period-cohort model was used to explore the age, period, and cohort effects on larynx cancer and predict future trends up to 2044. RESULTS: From 1990 to 2019, the age-standardized incidence rate of larynx cancer in China increased by 1.3% (95% CI 1.1 to 1.5) in males, but decreased by 0.5% (95% CI -0.1 to 0) in females. The age-standardized mortality rate of larynx cancer in China decreased by 0.9% (95% CI -1.1 to -0.6) and 2.2% (95% CI -2.8 to -1.7) in males and females, respectively. Among the four risk factors, smoking and alcohol use contributed to a heavier burden compared to occupational exposure to asbestos and sulfuric acid with respect to mortality. Age effects showed that the incidence and deaths of larynx cancer were concentrated in people older than 50 years old. Period effects exerted the most significant effect on larynx cancer incidence for males. In terms of cohort effects, people born in the earlier cohorts presented a higher risk of larynx cancer compared with the later cohorts. From 2020 to 2044, the age-standardized incidence rates of larynx cancer continued to increase in males, whereas the age-standardized mortality rates continued to decrease in both males and females. CONCLUSION: The burden of larynx cancer in China has a significant gender difference. The age-standardized incidence rates will continue to increase in males up to 2044. The disease pattern and risk factors of larynx cancer should be comprehensively studied to promote the development of timely intervention measures and relieve the burden effectively.

First report of leaf rot on Lonicera japonica caused by Rhizopus arrhizus in China.

Lonicera japonica is a perennial shrub that has been used since ancient times as a medicine to clear heat and detoxify poisons. Its branches (the vine of L. japonica) and unopened flower buds (honeysuckle) can be used as medicine to treat external wind heat or febrile disease fever (Shang, Pan, Li, Miao, & Ding, 2011). In July 2022, a serious disease was observed in L. japonica individuals planted in an area of experimental base of Nanjing Agricultural University (N 32°02', E 118°86'), Nanjing, Jiangsu Province, China. More than 200 Lonicera plants were surveyed, and the incidence of leaf rot in Lonicera leaves was over 80%. The initial symptoms were of chlorotic spots and gradual development of visible white mycelia and powdery substances (fungal spores) were observed on the leaves. Both the front and back of the leaves gradually appeared as brown diseased spots. Thus, a combination of multiple disease spots causes leaf wilting and the leaves eventually fall off. Leaves with typical symptoms were collected and cut into approximately 5 mm square fragments. The tissues were sterilized in 1% NaOCl for 90 s and 75% ethanol for 15 s and then washed with sterile water three times. The treated leaves were cultured on Potato Dextrose Agar (PDA) medium at 25℃. When mycelia grew around the leaf pieces, fungal plugs were collected along the outer edge of the colony and transferred to fresh PDA plates using a cork borer. Eight fungal strains with the same morphology were obtained after three rounds of subculturing. The colony was initially white with a fast growth rate, and occupied a 9-cm-diameter culture dish within 24 h. The colony turned gray-black in the later stages. After 2 days, small black sporangia spots appeared on top of the hyphae. The sporangia were yellow when immature, and black at maturity. The spores were oval with an average size of 29.6 (22.4-36.9) × 35.3 (25.8-45.2) µm (n = 50) in diameter. To identify the pathogen, fungal hyphae were scraped, and the fungal genome was extracted using a kit (BioTeke, Cat#DP2031). The internal transcribed spacer region (ITS) of the fungal genome was amplified with primers ITS1/ITS4, and the results of ITS sequencing were uploaded to the GenBank database with accession number OP984201. The phylogenetic tree was constructed using the neighbor-joining method with MEGA11 software. Phylogenetic analysis based on ITS showed that the fungus was grouped together with Rhizopus arrhizus (MT590591) and had high bootstrap support. Thus, the pathogen was identified as R. arrhizus. To verify Koch's postulates, 60 ml of a spore suspension (1×104 conidia/ml) was sprayed onto the surface of 12 healthy Lonicera plants, and the other 12 plants were sprayed with sterile water as a control. All plants were kept in the greenhouse at 25°C with 60% relative humidity. After 14 d, the infected plants showed symptoms similar to those of the original diseased plants. The strain was isolated again from the diseased leaves of artificially inoculated plants and verified as the original strain by sequencing. The results showed that R. arrhizus was the pathogen responsible for Lonicera leaf rot. Previous studies have shown that R. arrhizus causes garlic bulb rot (Zhang et al., 2022) and Jerusalem artichoke tuber rot (Yang et al., 2020). To our knowledge, this is the first report of R. arrhizus causing Lonicera leaf rot disease in China. Information regarding the identification of this fungus may be helpful for controlling the leaf rot disease.

Association of thiamine administration and prognosis in critically ill patients with heart failure.

Background: Thiamine deficiency is common in patients with heart failure, and thiamine supplement can benefit these patients. However, the association between thiamine administration and prognosis among critically ill patients with heart failure remains unclear. Thus, this study aims to prove the survival benefit of thiamine use in critically ill patients with heart failure. Methods: A retrospective cohort analysis was performed on the basis of the Medical Information Mart of Intensive Care-Ⅳ database. Critically ill patients with heart failure were divided into the thiamine and non-thiamine groups depending on whether they had received thiamine therapy or not during hospitalization. The association between thiamine supplement and in-hospital mortality was assessed by using the Kaplan-Meier (KM) method and Cox proportional hazard models. A 1:1 nearest propensity-score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPW) were also performed to ensure the robustness of the findings. Results: A total of 7,021 patients were included in this study, with 685 and 6,336 in the thiamine and non-thiamine groups, respectively. The kaplan-meier survival curves indicated that the thiamine group had a lower in-hospital mortality than the none-thiamine group. After adjusting for various confounders, the Cox regression models showed significant beneficial effects of thiamine administration on in-hospital mortality among critically ill patients with heart failure with a hazard ratio of 0.78 (95% confidence interval: 0.67-0.89) in the fully adjusted model. propensity-score matching and probability of treatment weighting analyses also achieved consistent results. Conclusion: Thiamine supplement is associated with a decreased risk of in-hospital mortality in critically ill patients with heart failure who are admitted to the ICU. Further multicenter and well-designed randomized controlled trials with large sample sizes are necessary to validate this finding.

Small RNAs: Efficient and miraculous effectors that play key roles in plant-microbe interactions.

Plants' response to pathogens is highly complex and involves changes at different levels, such as activation or repression of a vast array of genes. Recently, many studies have demonstrated that many RNAs, especially small RNAs (sRNAs), are involved in genetic expression and reprogramming affecting plant-pathogen interactions. The sRNAs, including short interfering RNAs and microRNAs, are noncoding RNA with 18-30 nucleotides, and are recognized as key genetic and epigenetic regulators. In this review, we summarize the new findings about defence-related sRNAs in the response to pathogens and our current understanding of their effects on plant-pathogen interactions. The main content of this review article includes the roles of sRNAs in plant-pathogen interactions, cross-kingdom sRNA trafficking between host and pathogen, and the application of RNA-based fungicides for plant disease control.

Human Neural Stem Cell Secretome Inhibits Neuron Heme Uptake and Ferroptosis in Intracerebral Hemorrhage Through Nrf-2 Signaling Pathway.

Intracerebral hemorrhage (ICH) is a common subtype of stroke with a very high mortality rate, but there is still no effective cure. Increasing evidence suggests that heme accumulation and neuronal ferroptosis play an important role in secondary injury after ICH. Neural stem cells (NSCs), as seed cells of the central nervous system, have received much attention due to their abundant paracrine product components and low immunogenicity. In this study, we focused on the protective mechanism of neural stem cell secretome (NSC-S) against neuronal ferroptosis in an ICH mouse model using hemin-induced in vitro models and collagenase type IV-induced in vivo models. The results showed that NSC-S could ameliorate neurological deficits and reduce neuronal injury in ICH model mice. In addition, NSC-S reduced heme uptake and ferroptosis in hemin-treated N2a cells in vitro. NSC-S induced the activation of Nrf-2 signaling pathway. However, these effects of NSC-S were abolished by the Nrf-2 inhibitor ML385. Notably, HSPE1 in NSC-S may be associated with the protection of NSC-S against hemin-injured neurons via the Nrf-2 signaling pathway. In summary, NSC-S protects against secondary neuronal injury in ICH via the Nrf-2 signaling pathway. Also, this functionality may be implemented by HSPE1.

Sclerotinia sclerotiorum Protoplast Preparation and Transformation.

Sclerotinia sclerotiorum causes white mold, leading to substantial losses on a wide variety of hosts around the world. Many genes encoding effector proteins play important roles in the pathogenesis of S. sclerotiorum. Therefore, establishment of a transformation system for the exploration of gene function is necessarily significant. Here, we introduce a modified protocol to acquire protoplasts for transformation and generate knockout strains, which completements the transformation system of S. sclerotiorum.

Plant Disease Resistance-Related Pathways Recruit Beneficial Bacteria by Remodeling Root Exudates upon Bacillus cereus AR156 Treatment.

The environmentally friendly biological control strategy that relies on beneficial bacterial inoculants to improve plant disease resistance is a promising strategy. Previously, it has been demonstrated that biocontrol bacteria treatments can change the plant rhizosphere microbiota but whether plant signaling pathways, especially those related to disease resistance, mediate the changes in rhizosphere microbiota has not been explored. Here, we investigated the complex interplay among biocontrol strains, plant disease resistance-related pathways, root exudates, rhizosphere microorganisms, and pathogens to further clarify the biocontrol mechanism of biocontrol bacteria by using plant signaling pathway mutants. Bacillus cereus AR156, which was previously isolated from forest soil by our laboratory, can significantly control tomato bacterial wilt disease in greenhouse and field experiments. Moreover, compared with the control treatment, the B. cereus AR156 treatment had a significant effect on the soil microbiome and recruited 35 genera of bacteria to enrich the rhizosphere of tomato. Among them, the relative rhizosphere abundance of nine genera, including Ammoniphilus, Bacillus, Bosea, Candidimonas, Flexivirga, Brevundimonas, Bordetella, Dyella, and Candidatus_Berkiella, was regulated by plant disease resistance-related signaling pathways and B. cereus AR156. Linear correlation analysis showed that the relative abundances of six genera in the rhizosphere were significantly negatively correlated with pathogen colonization in roots. These rhizosphere bacteria were affected by plant root exudates that are regulated by signaling pathways. IMPORTANCE Our data suggest that B. cereus AR156 can promote the enrichment of beneficial microorganisms in the plant rhizosphere by regulating salicylic acid (SA) and jasmonic acid (JA)/ethylene (ET) signaling pathways in plants, thereby playing a role in controlling bacterial wilt disease. Meanwhile, Spearman correlation analysis showed that the relative abundances of these beneficial bacteria were correlated with the secretion of root exudates. Our study reveals a new mechanism for SA and JA/ET signals to participate in the adjustment of plant resistance whereby the signaling pathways adjust the rhizosphere microecology by changing the root exudates and thus change plant resistance. On the other hand, biocontrol strains can utilize this mechanism to recruit beneficial bacteria by activating disease resistance-related signaling pathways to confine the infection and spread of pathogens. Finally, our data also provide a new idea for the in-depth study of biocontrol mechanisms.

An OsPRMT5-OsAGO2/miR1875-OsHXK1 module regulates rice immunity to blast disease.

Rice ARGONAUTE2 (OsAGO2) is a core component of the rice RNA-induced silencing complex (RISC), which is repressed by Magnaporthe oryzae (M. oryzae) infection. Whether and how OsAGO2-mediated gene silencing plays a role in rice blast resistance and which sRNAs participate in this process are unknown. Our results indicate that OsAGO2 is a key immune player that manipulates rice defense responses against blast disease. OsAGO2 associates with the 24-nt miR1875 and binds to the promoter region of HEXOKINASE1 (OsHXK1), which causes DNA methylation and leads to gene silencing. Our multiple genetic evidence showed that, without M. oryzae infection, OsAGO2/miR1875 RISC promoted OsHXK1 promoter DNA methylation and OsHXK1 silencing; after M. oryzae infection, the reduced OsAGO2/miR1875 led to a relatively activated OsHXK1 expression. OsHXK1 acts as a positive regulator of blast disease resistance that OsHXK1-OE rice exhibited enhanced resistance, whereas Cas9-Oshxk1 rice showed reduced resistance against M. oryzae infection. OsHXK1 may function through its sugar sensor activity as glucose induced defense-related gene expression and reactive oxygen species (ROS) accumulation in Nipponbare and OsHXK1-OE but not in Cas9-Oshxk1 rice. OsAGO2 itself is delicately regulated by OsPRMT5, which senses M. oryzae infection and attenuates OsAGO2-mediated gene silencing through OsAGO2 arginine methylation. Our study reveals an OsPRMT5-OsAGO2/miR1875-OsHXK1 regulatory module that fine tunes the rice defense response to blast disease.

Kurstakin Triggers Multicellular Behaviors in Bacillus cereus AR156 and Enhances Disease Control Efficacy Against Rice Sheath Blight.

Kurstakin is the latest discovered family of lipopeptides secreted by Bacillus spp. In this study, the effects of kurstakin on the direct antagonism, multicellularity, and disease control ability of Bacillus cereus AR156 were explored. An insertion mutation in the nonribosomal peptide synthase responsible for kurstakin synthesis led to a significant reduction of antagonistic ability of AR156 against the plant-pathogenic fungi Rhizoctonia solani, Ascochyta citrullina, Fusarium graminearum, and F. oxysporum f. sp. cubense. The loss of kurstakin synthesis ability significantly impaired the swarming motility of AR156 and reduced biofilm formation and amyloid protein accumulation. Although the loss of kurstakin synthesis ability did not reduce the competitiveness of AR156 under laboratory conditions, the colonization and environmental adaptability of the mutant was significantly weaker than that of wild-type AR156 on rice leaves. The cell surface of wild-type AR156 colonizing the leaf surface was covered by a thick biofilm matrix under a scanning electron microscope, but not the mutant. The colonization ability on rice roots and control efficacy against rice sheath blight disease of the mutant were also impaired. Thus, kurstakin participates in the control of plant diseases by B. cereus AR156 through directly inhibiting the growth of pathogenic fungi and improving long-term environmental adaptability and colonization of AR156 on the host surface by triggering multicellularity. This study explored the multiple functions of kurstakin in plant disease control by B. cereus.

Global, regional, and national years lived with disability due to blindness and vision loss from 1990 to 2019: Findings from the Global Burden of Disease Study 2019.

Purpose: This study aimed to provide a comprehensive assessment of burden estimates and the secular trend of blindness and vision loss, as measured by years lived with disability (YLDs), at the global, regional, and national levels. Methods: The age-standardized YLD rates (ASYRs) due to blindness and vision loss and its subtypes, including moderate vision loss, severe vision loss, blindness, and presbyopia, from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in the ASYRs due to blindness and vision loss. Results: In 2019, the global ASYRs per 100,000 population was 327.98 for blindness and vision loss, specifically, 85.81 for moderate vision loss, 74.86 for severe vision loss, 95.03 for blindness, and 62.27 for presbyopia. From 1990 to 2019, the ASYRs due to blindness and vision loss slightly decreased. Females showed higher ASYRs than males in 2019. The global highest ASYRs were observed in South Asia and sub-Saharan Africa. Negative associations were found between the burden estimates of blindness and vision loss and the sociodemographic index levels. The EAPCs of ASYRs in blindness and vision loss were significantly negatively correlated with the ASYRs in 1990 and positively correlated with human development indices in 2019. Conclusions: Globally, blindness and vision loss continue to cause great losses of healthy life. Reasonable resource allocation and health-service planning are needed for the prevention and early intervention of disabilities caused by vision loss.

Association of Red Cell Distribution Width-to-Platelet Ratio and Mortality in Patients with Sepsis.

Background: As a novel inflammatory index, the ratio of red cell distribution width (RDW) to platelet count (RPR) may have prognostic value in some critical illnesses. However, studies on the prognostic influence of RPR in patients with sepsis are few. This study is aimed at investigating the association between RPR levels and 28-day mortality in patients with sepsis. Methods: Data of patients with sepsis were obtained from the Medical Information Mart for Intensive Care III database. The best cut-off value was calculated by establishing the receiver operating characteristic curve (ROC), and the predictive ability of different indicators was compared through the area under the curve (AUC). The association between RPR levels and 28-day mortality was assessed using the Cox proportional hazards model. Restrictive cubic spline analysis was applied to the multivariable Cox model to investigate the nonlinear relationship between RPR and 28-day mortality. Results: A total of 3367 patients with sepsis were included in the study. A nonlinear relationship was observed between RPR and 28-day mortality, showing a trend of a first rapid increase and a gradual increase. For the prediction of mortality, the best cut-off value for RPR was 0.109, with an AUC of 0.728 (95% confidence interval [CI]: 0.709-0.747). The predictive capability of RPR was superior to those of RDW, platelet, SOFA score, and SAPS II score. After adjusting for various confounding factors, high RPR was significantly associated with increased mortality with adjusted hazard ratios of 1.210 (95% CI: 1.045-1.400) for categorical variables and 2.826 (95% CI: 2.025-3.944) for continuous variables. Conclusion: Elevated RPR level is significantly correlated with a high risk of 28-day mortality in patients with sepsis and can be a new predictor of patient prognosis.