Degree of paraxiality of radially polarized twisted multi-Gaussian Schell-model beams.

The degree of paraxiality (DOP) of a radially polarized twisted multi-Gaussian Schell-model (RPT MGSM) beam is discussed, and the influence of the source parameters on its DOP is studied. It is shown that the parameters of the beam source, including the boundary characteristic, the beam waist width, the coherence width of the source correlation, and the twist factor, have a significant impact on the DOP of the RPT MGSM beam. To explain the behaviors of the DOP, the far-field divergence angle of this beam is also discussed.

Allantoate Amidohydrolase OsAAH is Essential for Preharvest Sprouting Resistance in Rice.

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.

Potassium transporter OsHAK9 regulates seed germination under salt stress by preventing gibberellin degradation through mediating OsGA2ox7 in rice.

Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non-invasive micro-test technology results showed that OsHAK9 restricted K+ efflux in salt-exposed germinating seeds for the balance of K+/Na+. Disruption of OsHAK9 significantly reduced gibberellin 4 (GA4) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA3 treatment under salt stress. RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA-deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice.

Amyloid ß oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction.

BACKGROUND: Although abnormal accumulation of amyloid beta (Aß) protein is thought to be the main cause of Alzheimer's disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid ß induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aß 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. Aß oligomer stereotactic injection model was established to explain the relationship between Aß 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 Aß-injected model, suggesting a direct relationship between Aß and vascular dysfunction. Pericytes showed impaired features including low PDGFRß expression and increased pro-inflammatory chemokines secretion under the administration of Aß 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 Aß-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.

Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits.

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.

Chromatin attachment to the nuclear matrix represses hypocotyl elongation in Arabidopsis thaliana.

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.

Investigation on ozone formation mechanism and control strategy of VOCs in petrochemical region: Insights from chemical reactivity and photochemical loss.

To investigate disparities in VOCs pollution characteristics, O3 generation activity, and source apportionment outcomes resulting from photooxidation, online monitoring of 106 VOCs was conducted in Jinshan District, Shanghai from April to October 2020. The observed VOCs concentrations (VOCs-obs) were 47.1 ppbv and 59.2 ppbv for clear days (CD) and O3-polluted days (OPD), respectively. The increase in daytime concentrations of alkenes is a significant factor contributing to the enhanced atmospheric photochemical activity during the OPD period, corroborated by VOCs-loss, ozone formation potential (OFP), propy-equiv concentration, and LOH. The sensitivity analysis of O3-NOx-VOCs indicated that O3 formation was in a transitional regime towards NOx-limited conditions. The results of positive matrix factorization (PMF) demonstrated that refining and petrochemicals (20.8-25.0 %), along with oil and gas evaporation (15.6-16.7 %) were the main sources of VOCs concentrations. Notably, source apportionment based on VOCs-obs underestimated the contributions from sources of reactive components. It is worth highlighting that the sunlight impact & background source was identified as the major contributor to LOH (21.6 %) and OFP (25.3 %), signifying its significant role in O3 formation. This study reiterates the importance of controlling reactive VOC components to mitigate O3 pollution and provides a scientific foundation for air quality management, with emphasis on priority species and controlling sources.

Microbial colonization and chemically influenced selective enrichment of bacterial pathogens on polycarbonate plastic.

Plastic pollution in aquatic environments poses significant concerns due to its potential to serve as a refuge for aquatic pathogens. However, the role of plastic surfaces and microbial biofilm interfaces in facilitating pathogen development remains poorly understood. In this study, a microcosm setup was employed to investigate the interactions between plastics and the microbial community and examine the differences in bacterial community composition and potential pathogen occurrences between the plastisphere-biofilm and surrounding seawater. Community composition analysis combined with SEM observations over time indicated that biofilm extracellular polymeric substance formation over 14 days had a link with the relative abundance and succession patterns of pathogen taxa. Colony clusters were observed on biofilms from day 7 and coincided with higher bacterial pathogen dominance. On day 14, pathogen abundance overall decreased with a potentially degrading biofilm. Pseudomonas and Pseudoalteromonas were the dominant potential pathogen groups observed in the microcosm. When further subjected to chemical treatment as an imposed environmental stress over time, biofilm-associated Psuedoalteromonas sharply increased in abundance after three days of exposure, but quickly diminished by 14 days in favor of genera such as Acinetobacter, Pseudomonas, and Staphylococcus. These results suggest that environmental plastisphere-biofilms can promote the early selection, enrichment, and spread of pathogenic bacteria in the aquatic environment and could be later worsened under chemical and long-term pressure. This study provided new insights into the succession of pathogens in plastisphere biofilms, contributing to the understanding of pathogen risks involved in emerging plastisphere biofilms in light of global plastic pollution.

Profiling dynamics of the Southeast Asia's largest lake, Tonle Sap Lake.

Lakes, as vital components of the Earth's ecosystem with crucial roles in global biogeochemical cycles, are experiencing pervasive and irreparable worldwide losses due to natural factors and intensive anthropogenic interferences. In this study, we investigated the long-term dynamic patterns of the Tonle Sap Lake, the largest freshwater lake in the Mekong River Basin, using a series of hydrological data and remote sensing images between 2000 and 2020. Our findings revealed a significant decline in the annual average water level of the lake by approximately 2.1 m over 20 years, accompanied by an annual average reduction in surface area of about 1400 km2. The Tonle Sap Lake exhibited episodic declines in water level and surface area, characterized by the absence of flooding during the flood season and increasing aridity during the dry season. Furthermore, the shoreline of the lake has significantly advanced towards the lake in the northwestern and southern regions during the dry season, primarily due to sedimentation-induced shallowing of the lake edge depth and decreased water levels. In contrast, lake shorelines in the eastern region remained relatively stable due to the constructed embankments for the protection of the cultivated farmland. While the seasonal fluctuations of the Tonle Sap Lake are regulated by regional precipitation in the Mekong River Basin, the prolonged shrinking of the lake can be mainly ascribed to intensive anthropogenic activities. The interception of dams along the upper Mekong River has resulted in a decrease in the inflow to Tonle Sap Lake, exacerbating its shrinkage. Moreover, there are minor impacts from agricultural land expansion and irrigation on the lake. This study highlights the driving forces behind the evolution of Tonle Sap Lake, providing valuable information for lake managers to develop strategies aimed at conserving and restoring the ecological integrity of the Tonle Sap Lake.

Proposal of policies based on temporal-spatial dynamic characteristics and co-benefits of CO2 and air pollutants from vehicles in Shanghai, China.

In megacities, vehicle emissions face urgent challenges related to air pollution and CO2 control. To achieve the refinement of vehicle control policies for the co-control of air pollutants and CO2, this study established a vehicle emission inventory with high spatial and temporal resolution based on the hourly traffic flow in Shanghai and analyzed the spatial and temporal distribution characteristics of the real-time vehicle emissions. Meanwhile, a policy evaluation framework was constructed by combining pollutant emission predictions with quantitative co-control effect assessments. The results indicated that spatio-temporal variations in different air pollutants and CO2 could mainly be attributed to primary contributing vehicle types. The pollutants (CO2, CO and VOCs) primarily contributed by private cars exhibited a bimodal pattern in 24-h time series and their spatial distribution was concentrated in the urban city center. The spatial distribution of NOx and PM primarily contributed by heavy trucks was still obvious on non-urban center areas. Furthermore, the results of synergistic effect analysis revealed that the alternative energy replacement scenario demonstrated the most significant potential for the co-control. Based on temporal-spatial and co-benefit analysis, the precise control policy of vehicle emissions can be established through time-, region-, and model-control. This study provides references and research methods for the formulation of the vehicle refinement control policies in worldwide megacities.

Brain perivascular macrophages: current understanding and future prospects.

Brain perivascular macrophages are specialized populations of macrophages that reside in the space around cerebral vessels, such as penetrating arteries and venules. With the help of cutting-edge technologies, such as cell fate mapping and single-cell multi-omics, their multifaceted, pivotal roles in phagocytosis, antigen presentation, vascular integrity maintenance and metabolic regulation have more recently been further revealed under physiological conditions. Accumulating evidence also implies that perivascular macrophages are involved in the pathogenesis of neurodegenerative disease, cerebrovascular dysfunction, autoimmune disease, traumatic brain injury and epilepsy. They can act in either protective or detrimental ways depending on the disease course and stage. However, the underlying mechanisms of perivascular macrophages remain largely unknown. Therefore, we highlight potential future directions in research on perivascular macrophages, including the utilization of genetic mice and novel therapeutic strategies that target these unique immune cells for neuroprotective purposes. In conclusion, this review provides a comprehensive update on the current knowledge of brain perivascular macrophages, shedding light on their pivotal roles in central nervous system health and disease.

Progression of cognitive dysfunction in NPC survivors with radiation-induced brain necrosis: A prospective cohort.

BACKGROUND AND PURPOSE: The evidence of longitudinal changes in cognition in nasopharyngeal carcinoma (NPC) survivors with radiation-induced brain necrosis (RIBN) after radiotherapy (RT) remained insufficient. We aimed to estimate the clinical progression rate of cognitive decline and identify patients with differential decline rates. MATERIALS AND METHODS: Based on an ongoing prospective cohort study, NPC patients aged ≥18 years old and diagnosed with RIBN were included in this current analysis if they finished the time frame of 3-year follow-up and had at least twice cognition assessments. The Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive state. Linear mixed-effect models were used to analyze the annual progression rates of MoCA total and seven sub-items scores. RESULTS: Among 134 patients in this study, the transition probability from normal to mild/moderate cognitive dysfunction were 14.2 % (19/134) and 1.49 % (2/134) respectively during the median follow-up time of 2.35 years. The total MoCA score declined by -0.569 (SE 0.208) points annually (p = 0.008). Patients with ≤6 years of duration from RT to RIBN have higher annual progression rate of total scores [-0.851 (SE 0.321), p = 0.013; p for interaction = 0.041]. CONCLUSION: Our findings of the annual decline rate of cognition in NPC patients with RIBN from a 3-year longitudinal data, particularly for those who developed RIBN rapidly after RT, have important implications for the upcoming clinical trials designed to prevent or decrease cognitive decline in NPC patients with RIBN, regarding the selection of study patients and the calculation of sample size.

Diel Pattern of Microplastic Residues in Zebrafish.

As one of the emerging pollutants, microplastics (MPs) can be taken up by aquatic organisms through ingestion. However, little is known about the uptake pattern in organisms over time and the associated mechanisms of retention patterns. The present study aims to elucidate these patterns in fish, their relationship with light/dark conditions, and examine the uptake kinetic process of small-sized plastic pollutants, especially during the long-neglected dark period. Zebrafish were sampled every 2 h during the light and dark periods after exposure to an environmentally relevant concentration (100 items/L) of MPs. The results demonstrated that MP residues in zebrafish decreased during the dark period rather than increased over time. The MP retention rhythm and the swimming behavior of exposed zebrafish displayed a statistically significant light/dark variation. Moreover, a very strong and statistically significant positive correlation was found between the swimming speed of zebrafish and the number of MP residues in the gastrointestinal tracts of zebrafish. These results clearly demonstrate that fibrous MP residues in the fish have a discernible diel pattern. This work improves the understanding of the dynamic residual process of MPs in organisms and calls for further in-depth circadian toxicokinetic studies to better suit particle pollutants.

Identification of priority pollutants at an integrated iron and steel facility based on environmental and health impacts in the Yangtze River Delta region, China.

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.

Aquaculture bacterial pathogen database: Pathogen monitoring and screening in coastal waters using environmental DNA.

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.

Association of earlier age at menopause with risk of incident dementia, brain structural indices and the potential mediators: a prospective community-based cohort study.

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 (<40, 40-49, and ≥50 years) with ≥50 years taken as a reference. The primary outcome was all-cause dementia in a time-to-event analysis and the secondary outcomes included Alzheimer's disease, vascular dementia, and other types of dementia. In addition, we investigated the association between magnetic resonance (MR) brain structure indices with earlier menopause, and explored the potential underlying driven mediators on the relationship between earlier menopause and dementia. Findings: 2266 (1.47%) dementia cases were observed over a median follow-up period of 12.3 years. After adjusting for confounders, women with earlier menopause showed a higher risk of all-cause dementia compared with those ≥50 years (adjusted-HRs [95% CIs]: 1.21 [1.09-1.34] and 1.71 [1.38-2.11] in the 40-49 years and <40 years groups, respectively; P for trend <0.001). No significant interactions between earlier menopause and polygenic risk score, cardiometabolic factors, type of menopause, or hormone-replacement therapy strata were found. Earlier menopause was negatively associated with brain MR global and regional grey matter indices, and positively associated with white matter hyperintensity. The relationship between earlier menopause and dementia was partially mediated by menopause-related comorbidities including sleep disturbance, mental health disorder, frailty, chronic pain, and metabolic syndrome, with the proportion (95% CI) of mediation effect being 3.35% (2.18-5.40), 1.38% (1.05-3.20), 5.23% (3.12-7.83), 3.64% (2.88-5.62) and 3.01% (2.29-4.40), respectively. Multiple mediator analysis showed a combined effect being 13.21% (11.11-18.20). Interpretation: Earlier age at menopause was associated with risk of incident dementia and deteriorating brain health. Further studies are warranted to clarify the underlying mechanisms by which earlier age at menopause is linked to an increased risk of dementia, and to determine public health strategies to attenuate this association. Funding: National Natural Science Foundation of China, the Science and Technology Program of Guangzhou, the Key Area Research and Development Program of Guangdong Province, the China Postdoctoral Science Foundation, and the Guangdong Basic and Applied Basic Research Foundation.

Plastic mulching, and occurrence, incorporation, degradation, and impacts of polyethylene microplastics in agroecosystems.

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.

Revealing the impact of China's clean air policies on synergetic control of CO2 and air pollutant emissions: Evidence from Chinese cities.

China is presently confronted with the intricate challenge of simultaneously mitigating air pollution and decelerating the pace of climate change. An integrated perspective to investigate the synergetic control of CO2 and air pollutant emissions is in an urgent need. Using data for 284 Chinese cities from 2009 to 2017, we introduced an indicator called coupling and coordination degree of CO2 and air pollutant emissions control (CCD) and found an upward and spatial agglomeration trend of CCD distribution during the research period. Then, this study posed a specific focus on the impact of China's Air Pollution Prevention and Control Action Plan (APPCAP). The DID model revealed that implementation of the APPCAP resulted in a 4.0% increase in CCD for cities with special emission limits, attributed to industrial structural adjustments and the promotion of technology innovation. Furthermore, we also identified positive spillover effects of the APPCAP on neighboring control group cities situated within 350 km of the treatment group cities, providing an explanation for the spatial agglomeration trend observed in CCD distribution. These findings hold significant implications for the synergetic control in China and underscored the potential benefits of industrial structural adjustments and technology innovation in mitigating environmental pollution.

Identification of a key locus, qNL3.1, associated with seed germination under salt stress via a genome-wide association study in rice.

KEY MESSAGE: Two causal OsTTL and OsSAPK1 genes of the key locus qNL3.1 significantly associated with seed germination under salt stress were identified via a genome-wide association study, which could improve rice seed germination under salt stress. Rice is a salt-sensitive crop, and its seed germination determines subsequent seedling establishment and yields. In this study, 168 accessions were investigated for the genetic control of seed germination under salt stress based on the germination rate (GR), germination index (GI), time at which 50% germination was achieved (T50) and mean level (ML). Extensive natural variation in seed germination was observed among accessions under salt stress. Correlation analysis showed significantly positive correlations among GR, GI and ML and a negative correlation with T50 during seed germination under salt stress. Forty-nine loci significantly associated with seed germination under salt stress were identified, and seven of these were identified in both years. By comparison, 16 loci were colocated with the previous QTLs, and the remaining 33 loci might be novel. qNL3.1, colocated with qLTG-3, was simultaneously identified with the four indices in two years and might be a key locus for seed germination under salt stress. Analysis of candidate genes showed that two genes, the similar to transthyretin-like protein OsTTL and the serine/threonine protein kinase OsSAPK1, were the causal genes of qNL3.1. Germination tests indicated that both Osttl and Ossapk1 mutants significantly reduced seed germination under salt stress compared to the wild type. Haplotype analysis showed that Hap.1 of OsTTL and Hap.1 of OsSAPK1 genes were excellent alleles, and their combination resulted in high seed germination under salt stress. Eight accessions with elite performance of seed germination under salt stress were identified, which could improve rice seed germination under salt stress.

Amifostine-Loaded Nanocarrier Traverses the Blood-Brain Barrier and Prevents Radiation-Induced Brain Injury.

Radiation-induced brain injury (RIBI) is a severe, irreversible, or even life-threatening cerebral complication of radiotherapy in patients with head and neck tumors, and there is no satisfying prevention and effective treatment available for these patients. Amifostine (AMF) is a well-known free radical scavenger with demonstrated effectiveness in preventing radiation-induced toxicity. However, the limited permeability of AMF across the blood-brain barrier (BBB) when administered intravenously reduces the effectiveness of AMF in preventing RIBI. Herein, we construct a nanoparticle (NP) platform for BBB delivery of AMF. AMF is conjugated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)]-hydroxy succinamide [DSPE-PEG-NHS, PEG M 2000], and the product is DSPE-PEG-AMF. Then, the nanoparticles (DAPP NPs) were formed by self-assembly of poly(lactic-co-glycolic acid) (PLGA), DSPE-PEG-AMF, and polysorbate 80 (PS 80). PEG shields the nanoparticles from blood clearance by the reticuloendothelial system and lengthens the drug circulation time. PS 80 is used to encapsulate nanoparticles for medication delivery to the brain. The results of our study showed that DAPP NPs were able to effectively penetrate the blood-brain barrier (BBB) in healthy C57BL/6 mice. Furthermore, in a well-established mouse model of X-knife-induced brain injury, treatment with DAPP NPs (corresponding to 250 mg/kg AMF) was found to significantly reduce the volume of brain necrosis compared to mice treated with AMF (250 mg/kg). Importantly, the use of DAPP NPs was also shown to significantly mitigate the effects of radiation-induced neuronal damage and glial activation. This work presents a convenient brain-targeted AMF delivery system to achieve effective radioprotection for the brain, providing a promising strategy with tremendous clinical translation potential.