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Abstract Preharvest sprouting (PHS) is an undesirable trait that decreases yield and quality in rice production. Understanding the genes and regulatory mechanisms underlying PHS is of great significance for breeding PHS-resistant rice. In this study, we identified a mutant, preharvest sprouting 39 (phs39), that exhibited an obvious PHS phenotype in the field. MutMap+ analysis and transgenic experiments demonstrated that OsAAH, which encodes allantoate amidohydrolase, is the causal gene of phs39 and is essential for PHS resistance. OsAAH was highly expressed in roots and leaves at the heading stage and gradually increased and then weakly declined in the seed developmental stage. OsAAH protein was localized to the endoplasmic reticulum, with a function of hydrolyzing allantoate in vitro. Disruption of OsAAH increased the levels of ureides (allantoate and allantoin) and activated the tricarboxylic acid (TCA) cycle, and thus increased energy levels in developing seeds. Additionally, the disruption of OsAAH significantly increased asparagine, arginine, and lysine levels, decreased tryptophan levels, and decreased levels of indole-3-acetic acid (IAA) and abscisic acid (ABA). Our findings revealed that the OsAAH of ureide catabolism is involved in the regulation of rice PHS via energy and hormone metabolisms, which will help to facilitate the breeding of rice PHS-resistant varieties.

Abstract Cytosolic DNA sensors are a group of pattern recognition receptors (PRRs) that vary in structures, molecular mechanisms, and origins but share a common function to detect intracellular microbial DNA and trigger the innate immune response like type 1 interferon production and autophagy. Cytosolic DNA sensors have been proven as indispensable defenders against the invasion of many pathogens; however, growing evidence shows that self-DNA misplacement to cytoplasm also frequently occurs in non-infectious circumstances. Accumulation of cytosolic DNA causes improper activation of cytosolic DNA sensors and triggers an abnormal autoimmune response, that significantly promotes pathological progression. Neurodegenerative diseases are a group of neurological disorders characterized by neuron loss and still lack effective treatments due to a limited understanding of pathogenesis. But current research has found a solid relationship between neurodegenerative diseases and cytosolic DNA sensing pathways. This review summarizes profiles of several major cytosolic DNA sensors and their common adaptor protein STING. It also discusses both the beneficial and detrimental roles of cytosolic DNA sensors in the genesis and progression of neurodegenerative diseases.

Abstract Background Although abnormal accumulation of amyloid beta (Aβ) protein is thought to be the main cause of Alzheimer’s disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid β induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aβ deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding. Methods Two-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aβ oligomer stereotactic injection model was established to explain the relationship between Aβ and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms. Results Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aβ-injected model, suggesting a direct relationship between Aβ and vascular dysfunction. Pericytes showed impaired features including low PDGFRβ expression and increased pro-inflammatory chemokines secretion under the administration of Aβ in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. Conclusions Our results provide new insights into the pathogenic mechanism underlying Aβ-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.

Abstract The nuclear matrix is a nuclear compartment that has diverse functions in chromatin regulation and transcription. However, how this structure influences epigenetic modifications and gene expression in plants is largely unknown. In this study, we show that a nuclear matrix binding protein, AHL22, together with the two transcriptional repressors FRS7 and FRS12, regulates hypocotyl elongation by suppressing the expression of a group of genes known as SMALL AUXIN UP RNAs (SAURs) in Arabidopsis thaliana. The transcriptional repression of SAURs depends on their attachment to the nuclear matrix. The AHL22 complex not only brings these SAURs, which contain matrix attachment regions (MARs), to the nuclear matrix, but it also recruits the histone deacetylase HDA15 to the SAUR loci. This leads to the removal of H3 acetylation at the SAUR loci and the suppression of hypocotyl elongation. Taken together, our results indicate that MAR-binding proteins act as a hub for chromatin and epigenetic regulators. Moreover, we present a mechanism by which nuclear matrix attachment to chromatin regulates histone modifications, transcription, and hypocotyl elongation.

Coastal ecosystems are facing critical water quality deterioration, while the most convenient passage to the South China Sea, Beibu Gulf, has been under considerable pressure to its ecological environment due to rapid development and urbanization. In this study, we characterized the spatiotemporal change in the water quality in Beibu Gulf and proposed a machine learning approach to predict the water pollution level in Beibu Gulf on the basis of 5-year (2018–2022) observation data of ten water quality parameters from ten selected sites. Random forest (rf) and linear algorithms were utilized. Results show that a high frequency of exceedance of water quality parameters was observed particularly in summer and autumn, e.g., the exceeding rate of Dissolved Inorganic Nitrogen (DIN) at GX01, GX03, GX06, and GX07 station were 28.2~78.1% (average is 52.0%), 6.0~21.7% (average is 52.0%), 23.0~44.7% (average is 31.9%), and 5.2~33.4% (average is 21.2%), respectively. With regard to the spatial distribution, the pH, Water Salinity (WS), and Dissolved Oxygen (DO) values of stations inside the bay were overall lower than those of corresponding stations at the mouth of the bay and stations outside the bay. The concentrations of Chlorophyll-a concentration (except QZB) and nutrient salts showed a clearly opposite trend compared with the above concerned three parameters. For instance, the average Chl-a value of station GX09 was 22.5% higher than that of GX08 and GX10 between 2018 and 2022. Correlation analysis among water quality factors shows a significant positive correlation (r > 0.85) between Dissolved Inorganic Nitrogen (DIN) and NO3-N, followed by NO2-N and NH4-N, indicating that the main component of DIN is NO3-N. The forecasting results with machine learning also demonstrate the possibility to estimate the water quality parameters, such as chl-a concentration, DIN, and NH4-N in a cost-effective manner with prediction accuracy of approximately 60%, and thereby could provide near-real-time information to monitor the water quality of the Beibu Gulf. Predicting models initiated in this study could be of great interest for local authorities and the tourism and fishing industries.

Emissions from the iron and steel industry are a major source of air pollution. To investigate the composition characteristics, estimate the secondary transformation potential, and assess the ecological risk and human health risks of air pollutants from iron and steel industry, field measurements of volatile organic compounds (VOCs) and trace metals (TMs) were conducted simultaneously from 2020 to 2022 in the Yangtze River Delta (YRD) region, China. The average mixing concentration of VOCs (Σ64VOCs) was 58.2 ppbv. Alkanes, alkenes and aromatics were the major components. Benzene and ethylene were the most abundant VOC species. In the O3 season, the calculated OH loss rates (LOH) and ozone formation potential (OFP) were 10.87 S−1 and 181.74 ppbv, respectively, which increased 39.54% and 21.51% compared to the non-O3 season. Furthermore, the O3-VOCs-NOx sensitivity indicated that O3 formation was under the VOCs-limited regime. The average concentration of total 10 trace metals (Σ10TMs) was 226.8 ng m−3, Zn, Pb and Mn were the top abundant TM species. The results also found that Se was extremely contaminated; Pb and Zn was heavily to extremely contaminated; Cu, As and Ni were moderately to heavily contaminated. For lifetime cancer risk, the cumulative carcinogenic risks were 1.84E-5 for children, 6.14E-5 for adults and 1.83E-5 for workers. The carcinogenic risks of individual chemicals cannot be ignored, especially for Cr, Ni, benzene and 1,3-butadiene. The hazard index values for workers and residents were 0.53 and 2.23, respectively, suggesting a high non-carcinogenic risks to the exposed population. These findings deepen the understanding of the pollutant character of the iron and steel industry, and provide theoretical support for policy development on O3 pollution treatment and human health in the YRD region, China. For the study area, we recommend utilizing high-quality raw coal, reducing the volatile hydrocarbon content in the sinter feed, and installing absorption device for highly reactive VOC components at the exhaust outlet.

Increasingly diverse pathogen occurrence in coastal and mariculture areas demands improved monitoring platforms to prevent economic and public health implications. Accessible databases with up-to-date knowledge and taxonomy are critical for detecting and screening environmental pathogens. Condensed from over 3000 relevant reports in peer reviewed articles, we constructed an aquaculture bacterial pathogen database that provides specialized curation of over 210 bacterial pathogenic species impacting aquaculture. Application of the aquaculture bacterial pathogen database to environmental DNA metabarcoding monitoring data in Hong Kong coastal and mariculture waters effectively characterized regional pathogen profiles over a one-year period and improved identification of new potential pathogen targets. The results highlighted the increase in potential pathogen abundance related to aquaculture activity and the associated inorganic nitrogen load, which was chiefly due to the enrichment of Vibrio during the atypical dry winter season. The value of the aquaculture bacterial pathogen database for empowering environmental DNA-based approaches in coastal marine pathogen surveillance benefits water resource management and aquaculture development on a global scale.

Polyethylene microplastics have been detected in farmland soil, irrigation water, and soil organisms in agroecosystems, while plastic mulching is suggested as a crucial source of microplastic pollution in the agroecosystem. Plastic mulch can be broken down from plastic mulch debris to microplastics through environmental aging and degradation process in farmlands, and the colonization of polyethylene-degrading microorganisms on polyethylene microplastics can eventually enzymatically depolymerize the polyethylene molecular chains with CO2 release through the tricarboxylic acid cycle. The selective colonization of microplastics by soil microorganisms can cause changes in soil microbial community composition, and it can consequently elicit changes in enzyme activities and nutrient element content in the soil. The biological uptake of polyethylene microplastics and the associated disturbance of energy investment are the main mechanisms impacting soil-dwelling animal development and behavior. As polyethylene microplastics are highly hydrophobic, their presence among soil particles can contribute to soil water repellency and influence soil water availability. Polyethylene microplastics have been shown to cause impacts on crop plant growth, as manifested by the effects of polyethylene microplastics on soil properties and soil biota in the agroecosystems. This review reveals the degradation process, biological impacts, and associated mechanisms of polyethylene microplastics in agroecosystems and could be a critical reference for their risk assessment and management.

Summary: Background: To date, there is no homogeneous evidence of whether earlier age at menopause is associated with incident dementia. In addition, the underlying mechanism and driven mediators are largely unknown. We aimed to fill these knowledge gaps. Methods: This community-based cohort study included 154,549 postmenopausal women without dementia at enrolment (between 2006 and 2010) from the UK Biobank who were followed up until June 2021. We followed up until June 2021. Age at menopause was entered as a categorical variable (

Abstract Background Previous research suggested an association between maternal exposure to ambient air pollutants and the risk of congenital heart disease (CHD). However, the effect of individual prenatal exposure to indoor air pollutants on CHD occurrence was not reported. Methods We performed a hospital-based case–control study to investigate the association between personal air pollution exposure during pregnancy and the risk of CHD in offspring. A total of 44 cases and 75 controls were included from two hospitals in East China. We investigated maternal and residential environmental characteristics using a questionnaire and obtained personal indoor air samples to assess particulate matter (PM) and volatile organic compounds (VOCs) from 22–30 gestational weeks. Formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOCs), PM2.5, and PM10 were assessed. Logistic regression was performed to assess associations and interactions between individual indoor air pollutants and CHD after adjusting for confounders. The potential residential environmental factors affecting the risks of indoor air pollutants on CHD were also assessed. Results Median TVOC (0.400 vs. 0.005 mg/m3, P

Nutrient pollution in the coastal environment has been accelerated by progressively intensifying aquaculture activities. Excessive nutrients can lead to coastal eutrophication with serious economic and ecological consequences. In this study, we studied coastal planktonic microbial community over a year to understand the aquaculture impact on coastal water quality and function. We observed increased total inorganic nitrogen concentrations in active fish farms to favor the diverse Alpha- and Gammaproteobacteria. Bacterial community alpha diversity in fish farms was positively correlated with total inorganic nitrogen, and active fish farming co-influenced the bacterial structural composition and regional beta diversity. By analyzing the nitrogen cycle-related functional compositions and pathways using PICRUSt2 prediction on inferred genomes, we identified the contribution of over 600 bacterial species to four major pathways. Enhanced nitrogen load in active fish farms was positively correlated with elevated dissimilatory nitrate reduction and denitrification pathway abundances. Fallowed fish farms were characterized by a predicted high abundance of nirA and narB genes contributing to assimilatory nitrate reduction pathway due to the prevalence of Cyanobacteria. Overall, these results suggested active operation and short hiatus in coastal aquaculture practices could rapidly impact planktonic bacterial communities and further influence nitrogen cycling and associated processes. These findings will improve the understanding of the responses and interactions between microbiome and aquaculture activities. In a world of increasing aquaculture demands, this work has important implications for sustainable water resource management and development.

Summary: Background: The evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality. Methods: In this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a “watch-and-wait” policy). Findings: Of 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41). Interpretation: Among head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic. Funding: National Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).

Marine biofouling caused huge economic losses of maritime industries. We aim to develop high-efficient, less-toxic, and cost-effective antifoulants to solve the problems of biofouling. In this study, we described the antifouling compounds albofungin and its derivatives (albofungin A, chrestoxanthone A, and chloroalbofungin) isolated from the metabolites of bacterium Streptomyces chrestomyceticus BCC 24770, the construction of high-yield strains for albofungin production, and application of albofungin-based antifouling coatings. Results showed that these albofungins have potent antibiofilm activities against Gram-positive and Gram-negative bacteria and anti-macrofouling activities against larval settlement of major fouling organisms with low cytotoxicity. With the best antifouling activity and highest yield in bacterial culture, albofungin was subsequently incorporated with hydrolyzable and degradable copolymer to form antifouling coatings, which altered biofilm structures and prevented the settlement of macrofouling organisms in marine environments. Our results suggested that albofungins were promising antifouling compounds with potential application in marine environments.

In forest ecosystems, elevation gradient is one of the most influential factors on soil characteristics, vegetation types, and soil microorganisms. However, it remains unclear how the elevation gradient and the soil environment under its influence affect soil microbial communities under two distinct vegetation types. In this study, high-throughput sequencing technology from Illumina was utilized to examine the response of soil microbial communities to elevation and their driving factors in forests of Pinus taiwanensis and Pinus massoniana in various Jiangxi Province locales. The results demonstrated that the elevation gradients of the two pines had significant effects on soil organic carbon (SOC) and total nitrogen (TN), both in unimodal mode as well as on the alpha diversity of soil microbes. The community structure of soil bacteria is more sensitive to elevation than that of soil fungus. At different elevations in the two pine forests, Acidobacteria, Proteobacteria, Chloroflexi, Verrucomicrobia, Bacteroidetes, Patescibacteria, and Thaumarchaeota are the dominant bacterial phyla, and Ascomycota, Basidiomycota, and Mucoromycota are the dominant fungal phyla. This investigation revealed that SOC and TN were the two most influential factors on the alteration of the soil microbial community in two pine forests. In summary, there were substantial changes in soil microbial diversity and community composition across the two different pine forests, with elevation and soil characteristics (SOC and TN) serving as the primary drivers.

Abstract Background Rice growth is frequently affected by salinity. When exposed to high salinity, rice seed germination and seedling establishment are significantly inhibited. With the promotion of direct-seeding in Asia, improving rice seed germination under salt stress is crucial for breeding. Results In this study, an indica landrace Wujiaozhan (WJZ) was identified with high germinability under salt stress. A BC1F2 population derived from the crossing WJZ/Nip (japonica, Nipponbare)//Nip, was used to quantitative trait loci (QTL) mapping for the seed germination rate (GR) and germination index (GI) under H2O and 300 mM NaCl conditions. A total of 13 QTLs were identified, i.e. ten QTLs under H2O conditions and nine QTLs under salt conditions. Six QTLs, qGR6.1, qGR8.1, qGR8.2, qGR10.1, qGR10.2 and qGI10.1 were simultaneously identified under two conditions. Under salt conditions, three QTLs, qGR6.2, qGR10.1 and qGR10.2 for GR were identified at different time points during seed germination, which shared the same chromosomal region with qGI6.2, qGI10.1 and qGI10.2 for GI respectively. The qGR6.2 accounted for more than 20% of phenotypic variation under salt stress, as the major effective QTL. Furthermore, qGR6.2 was verified via the BC2F2 population and narrowed to a 65.9-kb region with eleven candidate genes predicted. Based on the microarray database, five candidate genes were found with high transcript abundances at the seed germination stage, of which LOC_Os06g10650 and LOC_Os06g10710 were differentially expressed after seed imbibition. RT-qPCR results showed the expression of LOC_Os06g10650 was significantly up-regulated in two parents with higher levels in WJZ than Nip during seed germination under salt conditions. Taken together, it suggests that LOC_Os06g10650, encoding tyrosine phosphatase family protein, might be the causal candidate gene for qGR6.2. Conclusions In this study, we identified 13 QTLs from a landrace WJZ that confer seed germination traits under H2O and salt conditions. A major salt-tolerance-specific QTL qGR6.2 was fine mapped to a 65.9-kb region. Our results provide information on the genetic basis of improving rice seed germination under salt stress by marker-assisted selection (MAS).

Introduction. Radiotherapy for patients with head and neck cancers raises their risk of aspiration pneumonia-related death. We aimed to develop and validate a model to predict radiation-associated aspiration pneumonia (RAP) among patients with dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). Materials and Methods. A total of 453 dysphagic patients with NPC were retrospectively recruited from Sun Yat-Sen Memorial Hospital from January 2012 to January 2018. Patients were randomly divided into training cohort (n=302) and internal validation cohort (n=151) at a ratio of 2 : 1. The concordance index (C-index) and calibration curve were used to evaluate the accuracy and discriminative ability of this model. Moreover, decision curve analysis was performed to evaluate the net clinical benefit. The results were externally validated in 203 dysphagic patients from the First People’s Hospital of Foshan. Results. Derived from multivariable analysis of the training cohort, four independent factors were introduced to predict RAP, including Kubota water drinking test grades, the maximum radiation dose of lymph node gross tumor volume (Dmax of the GTVnd), neutrophil count, and erythrocyte sedimentation rate (ESR). The nomogram showed favorable calibration and discrimination regarding the training cohort, with a C-index of 0.749 (95% confidence interval (CI), 0.681 to 0.817), which was confirmed by the internal validation cohort (C-index 0.743; 95% CI, 0.669 to 0.818) and the external validation cohort (C-index 0.722; 95% CI, 0.606 to 0.838). Conclusions. Our study established and validated a simple nomogram for RAP among patients with dysphagia after radiotherapy for NPC.

Estuarine sediments are increasingly contaminated by heavy metals as a result of urbanization and human activities. Continuous multi-heavy metal accumulation in the ecosystem can provoke new effects on top of the complex environmental interactions already present in estuarine ecosystems. It is important to study their integrated influence on imperative microbial communities to reflect on the environmental and ecological risks they may impose. Inductively coupled plasma optical emission spectroscopy analysis for five metals Cd, Cr, Cu, Pb, and Zn showed that Cr and Cu concentrations in intertidal sediments of the urbanized Yangtze River estuary in China have consistently exceeded respective threshold effect concentration (TEC) levels. The geo-accumulation and potential ecological risk index results of the five metals showed that all sampling sites were weakly to moderately polluted, and at considerable to high ecological risk, respectively. Redundancy and correlation analyses showed that Zn followed by Cr in the ecosystem were explanatory of the shifts in recorded microbial community structures. However, the spatial variation in metal concentrations did not correspond to the selection of metal resistance genes (MRGs). Unlike many other dominant bacterial taxa, most of the sulfate-reducing bacteria (SRB) and associated sulfate respiration as the dominant microbially contributed ecological function were found to negatively correlate with Zn and total heavy metal pollution. Zn concentration was proposed to be a potent indicator for heavy metal pollution-associated microbial community compositional shifts under urbanized estuarine conditions. The associations between heavy metals and estuarine microbial communities in this study demonstrate the influence of heavy metals on microbial community structure and adaptations that is often overshadowed by environmental factors (i.e., salinity and nutrients).

ObjectiveOur aim was to compare the clinical outcomes of patients treated with bevacizumab combined with corticosteroids and those with bevacizumab monotherapy from a radiation-induced brain necrosis (RN) registry cohort (NCT03908502).MethodsWe utilized clinical data from a prospective RN registry cohort (NCT03908502) from July 2017 to June 2020. Patients were considered eligible if they had symptomatic RN after radiotherapy for nasopharyngeal carcinoma (NPC) and received bevacizumab (5 mg/kg, two to four cycles) with a minimum follow-up time of 3 months. The primary outcome was a 2-month response rate determined by MRI and clinical symptoms. Secondary outcomes included quality of life [evaluated by the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire] and cognitive function (evaluated by the Montreal Cognitive Assessment scale) at 2 months, RN recurrence during follow-up, and adverse events.ResultsA total of 123 patients (34 in the combined therapy group and 89 in the monotherapy group) were enrolled in our study with a median follow-up time of 0.97 year [interquartile range (IQR) = 0.35–2.60 years]. The clinical efficacy of RN did not differ significantly between patients in these two groups [odds ratio (OR) = 1.642, 95%CI = 0.584–4.614, p = 0.347]. Furthermore, bevacizumab combined with corticosteroids did not reduce recurrence compared with bevacizumab monotherapy [hazard ratio (HR) = 1.329, 95%CI = 0.849–2.079, p = 0.213]. The most common adverse events of bevacizumab were hypertension (17.89%), followed by nosebleed (8.13%) and fatigue (8.13%). There was no difference in grade 2 or more severe adverse events between the two groups (p = 0.811).InterpretationOur results showed that the treatment strategy of combining bevacizumab with corticosteroids did not lead to better clinical outcomes for RN patients with a background of radiotherapy for nasopharyngeal carcinoma.

Abstract Background Rice (Oryza sativa L.) yield is seriously influenced by panicle exsertion (PE) and the uppermost internode (UI) through panicle enclosure or energy transport during grain-filling stages. We evaluated the traits of PE and UI of 205 rice accessions in two independent environments and performed genome-wide association (GWAS) to explore the key genes controlling PE and UI, which could be used to improve panicle enclosure in rice breeding. Results In this study, extensive genetic variation was found in both PE and UI among the 205 rice accessions, and 10.7% of accessions had panicle enclosure (PE/UI ≤ 0). Correlation analysis revealed that PE was significantly positively correlated with 1000-grain weight (1000-GW) but negatively correlated with heading date (HD), and UI was significantly positively correlated with HD but no significantly correlated with 1000-GW. A total of 22 and 24 quantitative trait loci (QTLs) were identified for PE and UI using GWAS, respectively. Eight loci for PE and nine loci for UI were simultaneously detected both in 2015 and in 2016, seven loci had adjacent physical positions between PE and UI, and ten loci for PE and seven loci for UI were located in previously reported QTLs. Further, we identified the CYP734A4 gene, encoding a cytochrome P450 monooxygenase, and the OsLIS-L1 gene, encoding a lissencephaly type-1-like protein, as causal genes for qPE14 and qUI14, and for qPE19, respectively. PE and UI were both significantly shorter in these two genes’ mutants than in WT. Allelic Hap.1/2/4 of CYP734A4 and Hap.1/2/4 of OsLIS-L1 increased PE, UI, PE/UI, and 1000-GW, but Hap.3 of CYP734A4 and Hap.3 of OsLIS-L1 reduced them. In addition, six candidate genes were also detected for four key novel loci, qPE16, qPE21, qUI1, and qUI18, that seemed to be related to PE and UI. Conclusions Our results provide new information on the genetic architecture of PE and UI in rice, confirming that the CYP734A4 and OsLIS-L1 genes participate in PE and UI regulation, which could improve our understanding of the regulatory mechanism of PE and UI for rice breeding in the future.

Mass suspension of anthropogenic activities is extremely rare, the quarantine due to the coronavirus disease 2019 (COVID-19) represents a natural experiment to investigate the impact of anthropogenic activities on air quality. The mitigation of air pollution during the COVID-19 lockdown has been reported from a global perspective; however, the air pollution levels vary in different regions. This study initiated a novel synthesis of multiple-year satellite observations, national ground measurements towards SO2, NO2 and O3 and meteorological conditions to evaluate the impact of the COVID-19 lockdown in Beihai, a specific city in a less developed area in southwest China, to reveal the potential implications of control strategies for air pollution. The levels of the major air pollutants during the COVID-19 lockdown (LP) and during the same period of previous years (SP) were compared and a series of statistical tools were applied to analyze the sources of air pollution in Beihai. The results show that air pollutant levels decreased with substantial diversity during the LP. Satellite-retrieved NO2 and SO2 levels during the LP decreased by 5.26% and 22.06%, while NO2, SO2, PM2.5 and PM10 from ground measurements during the LP were 25.6%, 2.7%, 22.2% and 22.2% lower than during SP, respectively. Ground measured SO2 concentrations during the LP were only 2.7% lower than during the SP, which may be attributed to uninterrupted essential industrial activities, such as power plants. Polar plots analysis shows that NO2 concentrations were strongly associated with local emission sources, such as automobiles and local industry. Additionally, the much lower levels of NO2 concentrations during the LP and the absence of an evening peak may highlight the significant impact of the traffic sector on NO2. The decrease in daily mean O3 concentrations during the LP may be associated with the reduction in NO2 concentrations. Indications in this study could be beneficial for the formulation of atmospheric protection policies.

To investigate composition characteristics and assess occupational health risks and odor pollution of volatile organic compounds (VOCs) from industrial activities in the Yangtze River Delta (YRD) region, China, one-year field measurements of VOCs were conducted simultaneously at an iron and steel industrial park (ISP), one chemical industrial park (CMP) and one petrochemical industrial park (PCP) from September, 2018 to August, 2019. The concentrations of VOCs were 80.2 ± 67.9 ppbv, 28.1 ± 27.2 ppbv and 144 ± 378 ppbv for ISP, CMP and PCP, respectively. Aromatics, alkanes and alkenes were the major components of VOCs at ISP, CMP and PCP, respectively. Moreover, the toluene to benzene ratios were 0.330 ± 0.302, 4.31 ± 6.48 and 1.84 ± 3.34, which generally showed the characteristics of combustion source for ISP, industrial activities for CMP and petrochemical industry for PCP, respectively. The hazard index values were 0.752 ± 0.438, 0.108 ± 0.248 and 0.090 ± 0.260 at ISP, CMP and PCP, which were generally lower than threshold limit value, suggesting a low noncarcinogenic risk for workers. Meanwhile, the 95th percentile LCR values of VOCs were 8.76 × 10−5, 1.15 × 10−5 and 1.00 × 10−5 at ISP, CMP and PCP, respectively, which were also under acceptable risk level, indicating a low carcinogenic risk. Benzene and 1,3-butadiene were main harmful substances for both noncarcinogenic and carcinogenic risks of VOCs. The odor levels of VOCs were 2.12 ± 4.21, 12.5 ± 28.7 and 1.01 ± 7.84 at ISP, CMP and PCP, respectively. Aromatics for ISP and sulfide compounds for CMP and PCP were primary pollutants for odor pollution. This work could improve the understanding of risk levels and odor characteristics of VOCs and benefit policy development on alleviating odor complaints and health risks for workers in YRD region, China.

Microbial communities are important indicators of aquatic ecosystem health, responsible for functional roles sustaining the ecosystem such as nutrient cycling, as well as environmental problems. Urbanized estuaries are vulnerable intersections between terrestrial and marine ecosystems and are susceptible to pressure and perturbation from both natural processes and human activities over time. The response by microbial communities toward changes in the environment should be closely monitored and studied. In this study, microbial communities in brackish intertidal sediments, sampled seasonally over a year along the coast of Yangtze River estuary, were analyzed using 16S rRNA gene sequencing. Potential compositional and functional changes in microbial communities resulting from temporal variation and associated physiochemical gradients in the environment were studied and notable patterns were observed over time. Summer season was recorded with the lowest microbial community α-diversity. For β-diversity, spatiotemporal differentiation in community structures was recorded with seasonal clustering. Proteobacteria was recorded as the most dominant phylum among all sampling sites throughout the year but its relative abundance showed no temporal changes. Instead, relative abundances of phyla Actinobacteria, Chloroflexi, and Verrucomicrobia were found to differ significantly over time, generally favoring the wet Spring and Summer. In contrast, temporal variation was observed for the class Deltaproteobacteria and some of the corresponding sulfate/sulfur-reducing bacterial genera, favoring the dry Autumn and Winter. However, there were no major temporal changes in ecological functions contributed by microbial communities throughout the study period. While results from redundancy analysis showed that the subtle changes in pH in the environment had the greatest impact on microbial community composition, the variation it explained remained relatively low. Alternatively, precipitation, distinguishing the dry and wet seasons of the subtropical monsoon climate zone, was suggested to be another potential key factor influencing microbial community composition and their relative abundances. The present study provides new data and insights on the impact of temporal variation on microbial community composition and ecological function in an urbanized estuarine ecosystem.

Butenolide derivatives have the potential to be effective and environmentally friendly antifouling agents. In the present study, a butenolide derivative was structurally modified into Boc-butenolide to increase its melting point and remove its foul smell. The structurally modified Boc-butenolide demonstrated similar antifouling capabilities to butenolide in larval settlement bioassays but with significantly lower toxicity at high concentrations. Release-rate measurements demonstrated that the antifouling compound Boc-butenolide could be released from polycaprolactone-polyurethane (PCL-PU)-based coatings to inhibit the attachment of foulers. The coating matrix was easily degraded in the marine environment. The performance of the Boc-butenolide antifouling coatings was further examined through a marine field test. The coverage of biofouler on the Boc-butenolide coatings was low after 2 months, indicating the antifouling potential of Boc-butenolide.

Abstract Although post-ischemic inflammation induced by the innate immune response is considered an essential step in the progression of cerebral ischemia injury, the role of triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of ischemic stroke remains to be elucidated. Here, we found that the transcriptional and post-transcriptional levels of TREM2 were increased in cultured primary microglia after oxygen-glucose deprivation and reoxygenation and in the ischemic penumbra of the cerebral cortex after middle cerebral artery occlusion (MCAO) and reperfusion in mice. TREM2 was mainly expressed in microglia, but not in astrocytes, neurons, or oligodendrocytes in mice subjected to MCAO. Manipulating TREM2 expression levels in vitro and in vivo significantly regulated the production of pro- and anti-inflammatory mediators after ischemic stroke. TREM2 overexpression markedly suppressed the inflammatory response and neuronal apoptosis. By contrast, TREM2 gene silencing intensified the inflammatory response, increased neuronal apoptosis and infarct volume, and further exacerbated neurological dysfunction. Our study demonstrated that TREM2 protects against cerebral ischemia/reperfusion injury through the aspect of post-ischemic inflammatory response and neuronal apoptosis. Pharmacological targeting of TREM2 to suppress the inflammatory response may provide a new approach for developing therapeutic strategies in the treatment of ischemic stroke and other cerebrovascular diseases.

Silver nanoparticles (AgNPs) are widely used in commercial applications as antimicrobial agents, but there have recently been increasing concerns raised about their possible environmental and health impacts. In this study, zebrafish embryos were exposed to two sizes of AgNP, 4 and 10 nm, through a continuous exposure from 4 to 96 h post-fertilisation (hpf), to study their uptake, impact and molecular defense responses. Results showed that zebrafish embryos were significantly impacted by 72 hpf when continuously exposed to 4 nm AgNPs. At concentrations above 0.963 mg/L, significant in vivo uptake and delayed yolk sac absorption was evident; at 1.925 mg/L, significantly reduced body length was recorded compared to control embryos. Additionally, 4 nm AgNP treatment at the same concentration resulted in significantly upregulated hypoxia inducible factor 4 (HIF4) and peroxisomal membrane protein 2 (Pxmp2) mRNA expression in exposed embryos 96 hpf. In contrast, no significant differences in terms of larvae body length, yolk sac absorption or gene expression levels were observed following exposure to 10 nm AgNPs. These results demonstrated that S4 AgNPs are available for uptake, inducing developmental (measured as body length and yolk sac area) and transcriptional (specifically HIF4 and Pxmp2) perturbations in developing embryos. This study suggests the importance of particle size as one possible factor in determining the developmental toxicity of AgNPs in fish embryos.

Lariat RNAs formed as by-products of splicing are quickly degraded by the RNA debranching enzyme 1 (DBR1), leading to their turnover. Null dbr1 mutants in both animals and plants are embryo lethal, but the mechanism underlying the lethality remains unclear. Here we characterized a weak mutant allele of DBR1 in Arabidopsis, dbr1-2, and showed that a global increase in lariat RNAs was unexpectedly accompanied by a genome-wide reduction in miRNA accumulation. The dbr1-2 mutation had no effects on expression of miRNA biogenesis genes or primary miRNAs (pri-miRNAs), but the association of pri-miRNAs with the DCL1/HYL1 dicing complex was impaired. Lariat RNAs were associated with the DCL1/HYL1 dicing complex in vivo and competitively inhibited the binding of HYL1 with pri-miRNA. Consistent with the impacts of lariat RNAs on miRNA biogenesis, over-expression of lariat RNAs reduced miRNA accumulation. Lariat RNAs localized in nuclear bodies, and partially co-localize with HYL1, and both DCL1 and HYL1 were mis-localized in dbr1-2. Together with our findings that nearly four hundred lariat RNAs exist in wild type plants and that these lariat RNAs also associate with the DCL1/HYL1 dicing complex in vivo, we thus propose that lariat RNAs, as decoys, inhibit miRNA processing, suggesting a hitherto unknown layer of regulation in miRNA biogenesis.

Increased concentrations of airborne particulate matter in megacities within China, caused by rapid economic growth, urbanization and industrialization, have become a major health concern. High energy consumption, emissions from a large fleet of on-road vehicles and intense industrial activities all contributed to the deterioration of urban air quality in China. In this study, we investigated the bioaccessibility of twelve particulate-bound trace elements (Al, Co, Cd, Cr, Cu, Fe, K, Mg, Mn, Ni, Pb, and Zn) using simulated lung fluids (Gamble’s solution (pH = 7.4) and artificial lysosomal fluid (ALF) (pH = 4.5)) following the collection of PM in Shanghai, a megacity in China, to gain a better understanding of their fate upon inhalation by adults and children. All the trace elements showed higher bioaccessibility in ALF, compared to that in the Gamble’s solution, due to lower pH and higher ionic strength of the former over the latter. In most cases, the kinetic response of trace elements in terms of their solubility followed a curvilinear pattern and approached near steady-state characteristics after a protracted period of incubation in the lung fluids. Health risk assessment was conducted for adults and children based on the measured bioaccessible fractions of trace elements, which showed significant excess lifetime cancer risk to both children and adults.

Easy shattering reduces yield from grain loss during rice ( L.) harvest. We characterized a nonshattering rice landrace Jiucaiqing from Taihu Lake valley in China. The breaking tensile strength (BTS; grams force, gf) of the grain pedicel was measured using a digital force gauge to evaluate the degree of shattering at 0, 7, 14, 21, 28, and 35 d after heading (DAH). The BTS of Jiucaiqing did not significantly decrease with increasing DAH, maintaining a level of 152.2 to 195.9 gf, while that of IR26 decreased greatly during 0 to 14 DAH and finally stabilized at ∼100 gf. Then the chromosome segment substitution lines (CSSLs) and near isogenic lines (NILs) of Jiucaiqing in IR26 background were developed for quantitative trait loci (QTL) mapping. Four putative QTL (, , , and ) for shattering were detected, and the was confirmed on chromosome 1. We further mapped to a 98.4-kb region, which contains 14 genes. Os01g62920 was considered to be a strong candidate for , which colocated with . Further quantitative real-time polymerase chain reaction (PCR) analyses confirmed that the QTL can significantly decrease the expression of shattering related genes (, , , , and ) especially at the middle development stage at 10 and 15 cm panicle length, which causes rice shattering decrease. The elite allele and the NIL with desirable agronomic traits identified in this study could be useful for rice breeding.

Replicating circular RNAs are independent plant pathogens known as viroids, or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs. The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demanding and time-consuming. We previously described an approach for homology-independent discovery of replicating circular RNAs by analysing the total small RNA populations from samples of diseased tissues with a computational program known as progressive filtering of overlapping small RNAs (PFOR). However, PFOR written in PERL language is extremely slow and is unable to discover those subviral pathogens that do not trigger in vivo accumulation of extensively overlapping small RNAs. Moreover, PFOR is yet to identify a new viroid capable of initiating independent infection. Here we report the development of PFOR2 that adopted parallel programming in the C++ language and was 3 to 8 times faster than PFOR. A new computational program was further developed and incorporated into PFOR2 to allow the identification of circular RNAs by deep sequencing of long RNAs instead of small RNAs. PFOR2 analysis of the small RNA libraries from grapevine and apple plants led to the discovery of Grapevine latent viroid (GLVd) and Apple hammerhead viroid-like RNA (AHVd-like RNA), respectively. GLVd was proposed as a new species in the genus Apscaviroid, because it contained the typical structural elements found in this group of viroids and initiated independent infection in grapevine seedlings. AHVd-like RNA encoded a biologically active hammerhead ribozyme in both polarities, and was not specifically associated with any of the viruses found in apple plants. We propose that these computational algorithms have the potential to discover novel circular RNAs in plants, invertebrates and vertebrates regardless of whether they replicate and/or induce the in vivo accumulation of small RNAs.

Seed vigor is an important characteristic of seed quality. In this study, one rice population of recombinant inbred lines (RILs) was used to determine the genetic characteristics of seed vigor, including the germination potential, germination rate, germination index and time for 50% of germination, at 4 (early), 5 (middle) and 6 weeks (late) after heading in two years. A total of 24 additive and 9 epistatic quantitative trait loci (QTL) for seed vigor were identified using QTL Cartographer and QTLNetwork program respectively in 2012; while 32 simple sequence repeat (SSR) markers associated with seed vigor were detected using bulked segregant analysis (BSA) in 2013. The additive, epistatic and QTL × development interaction effects regulated the dry maturity developmental process to improve seed vigor in rice. The phenotypic variation explained by each additive, epistatic QTL and QTL × development interaction ranged from 5.86 to 40.67%, 4.64 to 11.28% and 0.01 to 1.17%, respectively. The QTLs were rarely co-localized among the different maturity stages; more QTLs were expressed at the early maturity stage followed by the late and middle stages. Twenty additive QTLs were stably expressed in two years which might play important roles in establishment of seed vigor in different environments. By comparing chromosomal positions of these stably expressed additive QTLs with those previously identified, the regions of QTL for seed vigor are likely to coincide with QTL for grain size, low temperature germinability and seed dormancy; while 5 additive QTL might represent novel genes. Using four selected RILs, three cross combinations of seed vigor for the development of RIL populations were predicted; 19 elite alleles could be pyramided by each combination.

In this study, one rice population of recombinant inbred lines (RILs) was used to determine the genetic characteristics of seed reserve utilization during the early (day 6), middle (day 10) and late (day 14) germination stages. The seedling dry weight (SDW) and weight of the mobilized seed reserve (WMSR) were increased, while the seed reserve utilization efficiency (SRUE) decreased, during the process of seed germination. The SDW and WMSR were affected by the seed weight, while the SRUE was not affected by the seed weight. A total of twenty unconditional and twenty-one conditional additive QTLs and eight epistatic QTLs were identified at three germination stages, and the more QTLs were expressed at the late germination stage. Among them, twelve additive and three epistatic QTLs for SDW, eight additive and three epistatic QTLs for WMSR and thirteen additive and two epistatic QTLs for SRUE were identified, respectively. The phenotypic variation explained by each additive QTL, epistatic QTL and QTL × development interaction ranged from 6.10 to 23.91%, 1.79 to 6.88% and 0.22 to 2.86%, respectively. Two major additive QTLs qWMSR7.1 and qSRUE4.3 were identified, and each QTL could explain more than 20% of the total phenotypic variance. By comparing the chromosomal positions of these additive QTLs with those previously identified, eleven QTLs might represent novel genes. The best four cross combinations of each trait for the development of RIL populations were selected. The selected RILs and the identified QTLs might be applicable to improve rice seed reserve utilization by the marker-assisted selection approach.

The key to plant survival under NaCl salt stress is maintaining a low Na(+) level or Na(+)/K(+) ratio in the cells. A population of recombinant inbred lines (RILs, F(2:9)) derived from a cross between the salt-tolerant japonica rice variety Jiucaiqing and the salt-sensitive indica variety IR26, was used to determine Na(+) and K(+) concentrations in the roots and shoots under three different NaCl stress conditions (0, 100 and 120 mM NaCl). A total of nine additive QTLs were identified by QTL Cartographer program using single-environment phenotypic values, whereas eight additive QTLs were identified by QTL IciMapping program. Among these additive QTLs, five were identified by both programs. Epistatic QTLs and QTL-by-environment interactions were detected by QTLNetwork program in the joint analyses of multi-environment phenotypic values, and one additive QTL and nine epistatic QTLs were identified. There were three epistatic QTLs identified for Na(+) in roots (RNC), three additive QTLs and two epistatic QTLs identified for Na(+) in shoots (SNC), four additive QTLs identified for K(+) in roots (RKC), four additive QTLs and three epistatic QTLs identified for K(+) in shoots (SKC) and one additive QTL and one epistatic QTL for salt tolerance rating (STR). The phenotypic variation explained by each additive, epistatic QTL and QTL×environment interaction ranged from 8.5 to 18.9%, 0.5 to 5.3% and 0.7 to 7.5%, respectively. By comparing the chromosomal positions of these additive QTLs with those previously identified, five additive QTLs, qSNC9, qSKC1, qSKC9, qRKC4 and qSTR7, might represent novel salt tolerance loci. The identification of salt tolerance in selected RILs showed that a major QTL qSNC11 played a significant role in rice salt tolerance, and could be used to improve salt tolerance of commercial rice varieties with marker-assisted selection (MAS) approach.

The degree of paraxiality (DOP) of a diffracted multi-Gaussian beam is discussed. It is shown that the DOP of the multi-Gaussian beam will decrease as it is diffracted by a circular aperture, and the DOP of the diffracted multi-Gaussian beam is influenced by both the aperture radius and the characteristics of beam source. As an example, the dependence of the DOP on the aperture radius, the boundary characteristic, and the beam waist width is investigated. [ABSTRACT FROM AUTHOR]