Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

A new risk calculation model for complications of hepatectomy in adults over 75.

BACKGROUND: Owing to poor organ function reserve, older adults have a high risk of postoperative complications. However, there is no well-established system for assessing the risk of complications after hepatectomy in older adults. METHODS: This study aimed to design a risk assessment tool to predict the risk of complications after hepatectomy in adults older than 75 years. A total of 326 patients were identified. A logistic regression equation was used to create the Risk Assessment System of Hepatectomy in Adults (RASHA) for the prediction of complications (Clavien‒Dindo classification ≥ II). RESULTS: Multivariate correlation analysis revealed that comorbidity (≥ 5 kinds of disease or < 5 kinds of disease, odds ratio [OR] = 5.552, P < 0.001), fatigue (yes or no, OR = 4.630, P = 0.009), Child‒Pugh (B or A, OR = 4.211, P = 0.004), number of liver segments to be removed (≥ 3 or ≤ 2, OR = 4.101, P = 0.001), and adjacent organ resection (yes or no, OR = 1.523, P = 0.010) were independent risk factors for postoperative complications after hepatectomy in older persons (aged ≥ 75 years). A binomial logistic regression model was established to evaluate the RASHA score (including the RASHA scale and RASHA formula). The area under the curve (AUC) for the RASHA scale was 0.916, and the cut-off value was 12.5. The AUC for the RASHA formula was 0.801, and the cut-off value was 0.2106. CONCLUSION: RASHA can be used to effectively predict the postoperative complications of hepatectomy through perioperative variables in adults older than 75 years. TRIAL REGISTRATION: The Research Registry: researchregistry8531. https://www.researchregistry.com/browse-the-registry#home/registrationdetails/63901824ae49230021a5a0cf/ .

Efficacy of a modified FRAIL scale in predicting the peri-operative outcome of hepatectomy in older adults (aged ≥ 75 years): a model development study.

BACKGROUND: The FRAIL scale for evaluating frailty consists of five items: fatigue, resistance, aerobic, illness, and loss of weight. However, it is difficult to obtain a specific weight loss value. Since the Timed Up and Go Test (TUGT) is simple, accurate, and easy to perform, we replaced weight loss with the TUGT in the FRAIL scale, with the remaining four items unchanged, and named it the FRAIT scale. The aim of this study was to determine the value of the FRAIT scale in predicting the peri-operative outcome of hepatectomy. METHODS: This model development study was conducted between January 2017 and December 2021. The reliability, validity and area under the curve (AUC) of the FRAIL/FRAIT scales were calculated. The frailty status of patients aged ≥ 75 years who underwent hepatectomy was measured using the FRAIL/FRAIT scales. Logistic regression was used to compare the relationship between FRAIL/FRAIT scores/grades and perioperative outcomes. RESULTS: The AUCs for predicting operation duration, intraoperative bleeding, complications, and death based on the FRAIL score were 0.692, 0.740, 0.709, and 0.733, respectively, and those based on the FRAIT score were 0.700, 0.745, 0.708, and 0.724, respectively. The AUCs for predicting operation duration, intraoperative bleeding, complications, and death based on the FRAIL grade were 0.693, 0.735, 0.695, and 0.755, respectively, and those based on the FRAIT grades were 0.700, 0.758, 0.699, and 0.750, respectively. The FRAIL score has three effective predictors (intraoperative bleeding, complications, and death), while the FRAIT score has four effective predictors (operation duration, intraoperative bleeding, complications, and death). The FRAIL grade has two effective predictors (intraoperative bleeding and death), while the FRAIT grade has three effective predictors (operation duration, intraoperative bleeding, and death). CONCLUSIONS: This study describes a new and more effective tool for the assessment of preoperative frailty in older adults undergoing hepatectomy. The items of the FRAIT scale are easier to obtain than those of the FRAIL scale, and the predictive effect of the FRAIT scale is stronger than that of the FRAIL scale.

Single-Particle Hyperspectral Imaging for Monitoring of Gold Nanoparticle Aggregates in Macrophages.

Gold nanoparticles (Au NPs) have a promising future in the diagnosis and therapy of diseases owing to their unique photoelectric properties. In the body, monodisperse Au NPs may aggregate extracellularly and intracellularly, which influences their in vivo fate and physiological effects. However, due to the lack of a rapid, precise, and high throughput method for characterizing Au NP aggregates, the intricate aggregation process of Au NPs has not yet been fully understood. In order to overcome this obstacle, we develop a single-particle hyperspectral imaging method to identify Au NP aggregates, making use of the outstanding plasmonic properties of monodisperse and aggregated Au NPs. This method enables us to monitor the dynamic formation of Au NP aggregates in biological mediums and cells. Further single-particle hyperspectral imaging analysis reveals that following exposure to 100 nm Au NPs, the formation of Au NP aggregates in macrophages highly depends on exposure dosage and is less affected by exposure duration. In particular, surface coating, including PEGylation and protein corona, can considerably mitigate the intracellular aggregation of Au NPs. Our findings highlight that single-particle hyperspectral imaging is an efficient way for studying how Au NPs aggregate in biological scenarios.

Study on anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy.

BACKGROUND: Patients with malignant tumors are more likely to have psychological problems due to their worries about their life expectancy. To understand the psychological status of elderly patients with malignant liver tumor undergoing hepatectomy better, the study was designed to investigate the current situation of anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy and to analyze its related factors. METHODS: A total of 126 elderly patients with malignant liver tumor undergoing hepatectomy were selected as the research objects. The anxiety and depression of all subjects were evaluated by HADS (Hosptial Anxiety and Depression Scale). The correlation factors affecting the psychological state of elderly patients with malignant liver tumor undergoing hepatectomy were analyzed by linear regression method. RESULTS: The HADS-A score of elderly patients with malignant liver tumor undergoing hepatectomy was 8.79 ± 2.56, among which 37 patients were asymptomatic, 60 patients with suspicious symptoms, and 29 patients with definite symptoms. The HADS-D score was 8.40 ± 2.97, among which 61 patients were asymptomatic, 39 patients with suspicious symptoms, and 26 patients with definite symptoms. Multivariate analysis using linear regression method showed that FRAIL score, residence, and complication were significantly associated with anxiety and depression of elderly patients with malignant liver tumor undergoing hepatectomy. CONCLUSIONS: Anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy were obvious. FRAIL score, regional differences, and the complication were the risk factors for anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy. Improving frailty, reducing regional differences, and preventing complications is beneficial to alleviate the adverse mood of elderly patients with malignant liver tumor undergoing hepatectomy.

Quantitative Comparison of Gold Nanoparticle Delivery via the Enhanced Permeation and Retention (EPR) Effect and Mesenchymal Stem Cell (MSC)-Based Targeting.

There are still some gaps in existing knowledge in the field of cancer nanotheranostics, e.g., the efficiency of nanoparticle-loaded cells for targeted delivery. In the current study, gold nanoparticles (Au NPs) were delivered to tumors in both subcutaneous tumor and lung metastasis tumor models by intravenous injection of either free Au NPs or of human bone marrow mesenchymal stem cells (MSCs), which were loaded with endocytosed Au NPs. By making injections with the same dose of administrated Au NPs, it was possible to directly compare tumor targeting of both delivery modes. Hereby, the passive targeting of tumor by the plain Au NPs was facilitated by the enhanced permeation and retention (EPR) effect. Au NP retention by tumors, as well as tumor penetration, were found to be improved up to 2.4-to-9.3-fold when comparing the MSC-mediated delivery of Au NPs to the delivery of the plain Au NPs via EPR effect on day 7 post administration. While the absolute retention of Au NPs in the tumor remained low, our data show that, upon injection of the same amount of Au NPs, in fact MSC-mediated delivery is quantitatively higher than EPR-mediated delivery of NPs by half an order of magnitude.

Engineered Macrophages: A Safe-by-Design Approach for the Tumor Targeting Delivery of Sub-5 nm Gold Nanoparticles.

Ultrasmall nanoparticles (NPs) are a promising platform for the diagnosis and therapy of cancer, but the particles in sizes as small as several nanometers have an ability to translocate across biological barriers, which may bring unpredictable health risks. Therefore, it is essential to develop workable cell-based tools that can deliver ultrasmall NPs to the tumor in a safer manner. Here, this work uses macrophages as a shuttle to deliver sub-5 nm PEGylated gold (Au) NPs to tumors actively or passively, while reducing the accumulation of Au NPs in the brain. This work demonstrates that sub-5 nm Au NPs can be rapidly exocytosed from live macrophages, reaching 45.6% within 24 h, resulting in a labile Au NP-macrophage system that may release free Au NPs into the blood circulation in vivo. To overcome this shortcoming, two straightforward methods are used to engineer macrophages to obtain "half-dead" and "dead" macrophages. Although the efficiency of engineered macrophages for delivering sub-5 nm Au NPs to tumors is 2.2-3.8% lower than that of free Au NPs via the passive enhanced permeability and retention effect, this safe-by-design approach can dramatically reduce the accumulation of Au NPs in the brain by more than one order of magnitude. These promising approaches offer an opportunity to expand the immune cell- or stem cell-mediated delivery of ultrasmall NPs for the diagnosis and therapy of diseases in a safer way in the future.

Perioperative factors related to the prognosis of elderly patients with hepatocellular carcinoma.

BACKGROUND: Hepatic resection is a potentially curative treatment for patients with hepatocellular carcinoma (HCC). The treatment of elderly patients with HCC has always been difficult. With the development of geriatrics and geriatric surgery, the number of elderly patients with HCC undergoing hepatectomy has gradually increased. To further improve the long-term prognosis of elderly patients with hepatocellular carcinoma undergoing surgery, it is necessary to study the related perioperative factors. Our aim was to study the impact of preoperative and intraoperative factors on the long-term survival of elderly patients with HCC who underwent hepatectomy. METHODS: A total of 151 elderly patients with HCC who underwent hepatectomy were retrospectively studied. Univariate and multivariate Cox regression analyses were performed for preoperative- and intraoperative-related prognostic factors. RESULTS: The 1-, 3-, 5- and 10-year overall survival rates of elderly patients with HCC who underwent resection were 79.5%, 60.8%, 46.6%, and 25.4%, respectively. Multivariate analyses identified four independent predictors of long-term prognosis: Child-Pugh grade (B/C versus A: HR[hazard ratio] = 2.318, P = 0.019), alpha-fetoprotein value (> 20 ng/ml versus ≤ 20 ng/ml: HR = 1.972, P = 0.005), resection style (anatomical versus no anatomical: HR = 1.976, P = 0.006), and intraoperative blood loss (> 400 ml versus ≤ 400 ml: HR = 2.008, P = 0.003). CONCLUSIONS: Poor survival of elderly patients with HCC who underwent hepatectomy was correlated with the preoperative and intraoperative factors of Child-Pugh grade, Alpha-fetoprotein value, resection style, and intraoperative blood loss.

Effect of perioperative factors on the prognosis of patients with hepatocellular carcinoma who underwent hepatectomy.

BACKGROUND: Hepatic resection is a potentially curative treatment for patients with hepatocellular carcinoma (HCC). Controversy persists regarding preoperative and intraoperative characteristics related to patient survival in various medical institutes. This study aimed to evaluate the impact of preoperative and intraoperative factors on the long-term survival of patients with HCC who underwent hepatectomy. METHODS: Data on 455 patients with HCC who underwent hepatectomy over a 20-year period were retrospectively reviewed. Univariate and multivariate Cox regression analyses were performed for preoperative- and intraoperative-related prognostic factors. RESULTS: The 1-, 3-, 5-, and 10-year overall survival rates of patients with HCC who underwent resection were 76.3%, 57.9%, 46.7%, and 27.4%, respectively. Multivariate analyses identified four independent predictors of long-term prognosis-sex (male versus female, hazard ratio [HR] = 2.732, p = 0.026); differentiation (poor versus well, HR = 2.037, p = 0.030); total bilirubin value (µmol/L, HR = 1.056, p = 0.033); and intraoperative blood transfusion (no transfusion versus transfusion, HR = 0.417, p = 0.002). Hepatitis virus B infection (negative versus positive, HR = 0.669, p = 0.232) and resection style (anatomical versus nonanatomical, HR = 0.698, p = 0.181) were not associated with survival. DISCUSSION: Based on this 20-year study, poor survival of patients with HCC who underwent hepatectomy was correlated with preoperative and intraoperative factors including male sex, poor differentiation, increased total bilirubin levels, and intraoperative blood transfusion.

Individualized risk estimation for postoperative pulmonary complications after hepatectomy based on perioperative variables.

BACKGROUND: At present, there is no perfect system to evaluate pulmonary complications of liver surgery using perioperative variables. AIM: To design and verify a risk assessment system for predicting postoperative pulmonary complications (PPCs) after hepatectomy based on perioperative variables. METHODS: A retrospective analysis was performed on 1633 patients who underwent liver surgery. The variables were screened using univariate and multivariate analyses, and graded scores were assigned to the selected variables. Logistic regression was used to develop the liver operation pulmonary complication scoring system (LOPCSS) for the prediction of PPCs. The LOPCSS was verified using the receiver operating characteristic curve. RESULTS: According to the multivariate correlation analysis, the independent factors which influenced PPCs of liver surgery were age [≥ 65 years old/< 65 years old, odds ratio (OR) = 1.926, P = 0.011], medical diseases requiring drug treatment (yes/no, OR = 3.523, P < 0.001), number of liver segments to be removed (≥ 3/≤ 2, OR = 1.683, P = 0.002), operation duration (≥ 180 min/< 180 min, OR = 1.896, P = 0.004), and blood transfusion (yes/no, OR = 1.836, P = 0.003). The area under the curve (AUC) of the LOPCSS was 0.742. The cut-off value of the expected score for complications was 5. The incidence of complications in the group with ≤ 4 points was significantly lower than that in the group with ≥ 6 points (2.95% vs 33.40%, P < 0.001). Furthermore, in the validation dataset, the corresponding AUC of LOPCSS was 0.767. CONCLUSION: As a novel and simplified assessment system, the LOPCSS can effectively predict PPCs of liver surgery through perioperative variables.

Establishment of an Assessment System for the Prediction of Severe Post-operative Complications after Hepatectomy Based on Preoperative Parameters.

OBJECTIVE: At present, there is no appropriate system to evaluate the severe complications of liver surgery through the preoperative factors. This study aimed to design and verify a risk assessment system for the prediction of severe post-operative complications after a hepatectomy based on the preoperative parameters. METHODS: A retrospective analysis was performed on 1732 patients who had undergone liver surgery. The severity of the complications was graded by Accordion Severity Grading of post-operative complications. The variables were screened by multivariate analysis, and graded scores were assigned to the selected variables. A logistic regression equation was used to form the liver operation risk formula (LORF) for the prediction of severe post-operative complications. The LORF was verified by the receiver operating characteristic (ROC) curve. RESULTS: The multivariate correlation analysis revealed the independent influencing factors of the severe post-operative complications of liver surgery were Child-Pugh grade (OR=4.127; P<0.001), medical diseases requiring drug treatment (OR=3.092; P<0.001), the number of liver segments to be removed (OR=2.209; P=0.006), organ invasion (OR=4.538; P=0.024), and pathological type (OR=4.023; P=0.002). The binomial logistic regression model was established to obtain the calculation formula (LORF) of the severe complication risk. The area under the ROC curve (AUC) of the LORF was 0.815. The cut-off value of the expected probability of severe complications was 0.3225 (32.25%). Furthermore, in the validation data set, the corresponding AUC of the LORF was 0.829. CONCLUSION: As a novel and simplified assessment system, the LORF could effectively predict the severe post-operative complications of liver surgery through the preoperative factors, and therefore it could be used to evaluate the risk of severe liver surgical complications before surgery.

Effect of Postoperative ω-3 Fatty Acid Immunonutritional Therapy on NK Cell Gene Methylation in Elderly Patients with Gastric Cancer.

OBJECTIVE: This study aims to investigate the effect of ω-3 fatty acid immunonutritional therapy on natural killer (NK) cell gene methylation and function in elderly patients with gastric cancer. METHODS: A total of 70 cases of elderly patients with gastric cancer were randomized into the ω-3 fatty acid group and placebo group, according to the type of nutritional support administered. The methylation status of the tumor necrosis factor (TNF)-α gene promoter in peripheral NK cells was detected by methylation specific polymerase chain reaction, and the TNF-α level in peripheral NK cells was detected by enzyme-linked immunosorbent assay. RESULTS: After 14 days of immunonutritional therapy with ω-3 fatty acid or placebo, patients in the ω-3 group had significantly higher average NK cell activity (0.27 vs. 0.24, P=0.013) and lower percentages of TNF-α gene promoter methylation (25.7% vs. 60%, P<0.05) than the placebo group. However, there were no significant differences in the concentration of albumin, prealbumin and TNF-α in serum, and the NK cell count between the ω-3 group and placebo group. CONCLUSION: The postoperative application of ω-3 fatty acid may improve the activity of NK cells, which is correlated to the methylation status of the TNF-α gene promoter.

Emerging health risks and underlying toxicological mechanisms of uranium contamination: Lessons from the past two decades.

Uranium contamination is a global health concern. Regarding natural or anthropogenic uranium contamination, the major sources of concern are groundwater, mining, phosphate fertilizers, nuclear facilities, and military activities. Many epidemiological and laboratory studies have demonstrated that environmental and occupational uranium exposure can induce multifarious health problems. Uranium exposure may cause health risks because of its chemotoxicity and radiotoxicity in natural or anthropogenic scenarios: the former is generally thought to play a more significant role with regard to the natural uranium exposure, and the latter is more relevant to enriched uranium exposure. The understanding of the health risks and underlying toxicological mechanisms of uranium remains at a preliminary stage, and many controversial findings require further research. In order to present state-of-the-art status in this field, this review will primarily focus on the chemotoxicity of uranium, rather than its radiotoxicity, as well as the involved toxicological mechanisms. First, the natural or anthropogenic uranium contamination scenarios will be briefly summarized. Second, the health risks upon natural uranium exposure, for example, nephrotoxicity, bone toxicity, reproductive toxicity, hepatotoxicity, neurotoxicity, and pulmonary toxicity, will be discussed based on the reported epidemiological cases and laboratory studies. Third, the recent advances regarding the toxicological mechanisms of uranium-induced chemotoxicity will be highlighted, including oxidative stress, genetic damage, protein impairment, inflammation, and metabolic disorder. Finally, the gaps and challenges in the knowledge of uranium-induced chemotoxicity and underlying mechanisms will be discussed.

OsPAL2-1 Mediates Allelopathic Interactions Between Rice and Specific Microorganisms in the Rhizosphere Ecosystem.

The use of plant allelopathy to control weeds in the field has been generally recognized as a win-win strategy because it is an environmentally friendly and resource-saving method. The mechanism of this natural weed-control method relies on allelochemicals, the rhizosphere microbiome, and their bio-interaction, and exploring the link between allelochemicals and specific microbes helps accelerate the application of allelopathic characteristics in farming. In this study, we used allelopathic rice PI312777 (PI), its genetically modified OsPAL2-1 repression (PR) or overexpression (PO) lines, and non-allelopathic rice Lemont (Le) as donor plants to reveal the bio-interaction between rice allelochemicals and rhizosphere specific microorganisms. The results showed a higher content of phenolic acid exudation from the roots of PI than those of Le, which resulted in a significantly increased population of Myxococcus in the rhizosphere soil. Transgenic PO lines exhibited increasing exudation of phenolic acid, which led to the population of Myxococcus xanthus in the rhizosphere soil of PO to be significantly increased, while PR showed the opposite result in comparison with wild type PI. Exogenous application of phenolic acid induced the growth of M. xanthus, and the expressions of chemotaxis-related genes were up-regulated in M. xanthus. In addition, quercetin was identified in the culture medium; according to the bioassay determination, a quercetin concentration of 0.53 mM inhibited the root length by 60.59%. Our study indicates that OsPAL2-1 is among the efficient genes that regulate rice allelopathy by controlling the synthesis of phenolic acid allelochemicals, and phenolic acid (ferulic acid, FA) induces the chemotactic aggregation of M. xanthus, which promoted the proliferation and aggregation of this microbe. The potential allelochemical, quercetin was generated from the FA-induced M. xanthus cultured medium.

The Crucial Role of Environmental Coronas in Determining the Biological Effects of Engineered Nanomaterials.

In aquatic environments, a large number of ecological macromolecules (e.g., natural organic matter (NOM), extracellular polymeric substances (EPS), and proteins) can adsorb onto the surface of engineered nanomaterials (ENMs) to form a unique environmental corona. The presence of environmental corona as an eco-nano interface can significantly alter the bioavailability, biocompatibility, and toxicity of pristine ENMs to aquatic organisms. However, as an emerging field, research on the impact of the environmental corona on the fate and behavior of ENMs in aquatic environments is still in its infancy. To promote a deeper understanding of its importance in driving or moderating ENM toxicity, this study systemically recapitulates the literature of representative types of macromolecules that are adsorbed onto ENMs; these constitute the environmental corona, including NOM, EPS, proteins, and surfactants. Next, the ecotoxicological effects of environmental corona-coated ENMs on representative aquatic organisms at different trophic levels are discussed in comparison to pristine ENMs, based on the reported studies. According to this analysis, molecular mechanisms triggered by pristine and environmental corona-coated ENMs are compared, including membrane adhesion, membrane damage, cellular internalization, oxidative stress, immunotoxicity, genotoxicity, and reproductive toxicity. Finally, current knowledge gaps and challenges in this field are discussed from the ecotoxicology perspective.

Metabolite profiling of rhizosphere soil of different allelopathic potential rice accessions.

BACKGROUND: Identification of the allelopathy-interrelated metabolites from the allelopathic rice rhizosphere is crucial to understand the allelopathic mechanism of rice, which in turn can promote its applications to farming. In this study, the metabolites from the rhizosphere soil of five different rice lines, including allelopathic rice accession PI312777 (PI) and non-allelopathic rice accession Lemont (Le) as well as their genetic derivatives (e.g., phenylalanine ammonia-lyase (PAL) gene overexpression transgenic lines of PI and Le, namely, PO and LO respectively, and PAL RNA interference line of PI, namely, PR) were identified and comparatively analyzed to explore the positive compounds that are involved in the process of rice allelopathy. RESULTS: The results showed that 21 non-polar compounds and 21 polar compounds differed in content in the rhizosphere soil of PI and Le, which include several volatile fatty acids and long-chain fatty acids. The relative contents of fatty acids also differed between PAL overexpressing or RNA interference (RNAi)-silenced line and their wild-type respectively. Acetic acid content also differed among groups, i.e., it is higher in the high allelopathic potential rice. Further analysis showed that different metabolites from the ADS8 resin-extracted phase were more abundant than that those from the ADS21 resin-extracted phase, suggesting that the allelochemicals in root exudates of allelopathic rice are mainly non-polar substances. KEGG annotation of these differential metabolites revealed that these compounds were related to nutrient metabolism, secondary metabolite synthesis, signaling substance synthesis, and toxin degradation. CONCLUSIONS: Rice allelochemicals deposited in the ADS8 resin-extracted phase were more abundant than those in the ADS21 resin-extracted phase. Allelochemicals in root exudates of allelopathic rice are mainly non-polar substances, and long-chain fatty acids are considered as allelopathy interrelated metabolites.

Silver nanoparticles compromise the development of mouse pubertal mammary glands through disrupting internal estrogen signaling.

Despite numerous studies on the environmental health and safety (EHS) of silver nanoparticles (AgNPs), most studies looked into their gross toxicities with rather limited understanding on their labyrinthine implicit effects on the target sites, such as the endocrine system. Burgeoning evidence documents the disrupting effects of AgNPs on endocrine functions; however, little research has been invested to recognize the potential impacts on the mammary gland, a susceptible estrogen-responsive organ. Under this setting, we here aimed to scrutinize AgNP-induced effects on the development of pubertal mammary glands at various concentrations that bear significant EHS relevance. We unearthed that AgNPs could accumulate in mouse mammary glands and result in a decrease in the percentage of ducts and terminal ducts in the adult mice after chronic exposure. Strikingly, smaller sized AgNPs showed greater capability to alter the pubertal mammary development than larger sized particles. Intriguingly, mechanistic investigation revealed that the reduction of epithelial proliferation in response to AgNPs was ascribed to reduced ERα expression, which, at least partially, accounted for diseased epithelial morphology in mammary glands. Meanwhile, the decline in fibrous collagen deposition around the epithelium was found to contribute to the compromised development of mammary glands under the exposure of AgNPs. Moreover, as an extension of the mechanism, AgNPs diminished serum levels of estradiol in exposed animals. Together, these results uncovered a novel toxicity feature of AgNPs: compromised development of mouse pubertal mammary glands through the endocrine-disrupting actions. This study would open a new avenue to unveil the EHS impacts of AgNPs.

Ageing alters the physicochemical properties of silver nanoparticles and consequently compromises their acute toxicity in mammals.

Despite numerous investigations into AgNP-induced toxicity, little has been taken into consideration the potential health impacts of aged AgNPs in comparison to fresh AgNPs. In the current study, we scrutinized the potential effects of aged AgNPs in animals. We first found that AgNPs underwent morphological transformations after natural ageing in aqueous solution upon exposure to air and sunlight for 9 days, as characterized by significant aggregation with increase of particle size approximately by 2 fold. Meanwhile, dissolved Ag ions from aged AgNPs increased by 33% compared to fresh AgNPs. Strikingly, the acute exposure results showed that aged AgNPs induced lower toxicity in mice relative to fresh AgNPs. Aged AgNPs caused milder local inflammation in the peritoneal cavity of mice, as evidenced by 63% reduction of tumor necrosis factor α (TNF-α) than that induced by fresh AgNPs. The deposition mass of aged AgNPs in the liver, spleen, lung and kidney was diminished by 69%, 39%, 83% and 40%, respectively, compared to the distribution profiles in response to fresh AgNPs. Whereby, milder splenic hyperemia was observed, and no significant hepatoxicity was found. Additionally, aged AgNPs provoked milder increase of periphery leukocytes and malondialdehyde (MDA) in mice in comparison to fresh AgNPs. Taken together, this study unraveled that the ageing process elicited remarkable alterations to physicochemical properties and toxic effects as well. This study would provide new insights into the potential health impacts of AgNPs under transformation-determined exposure scenarios.