COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment: A Randomized Clinical Trial.

Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

Water temperature governs organophosphate ester dynamics in the aquatic food chain of Poyang Lake.

Organophosphate esters (OPEs) are increasingly recognized as pervasive environmental contaminants, primarily from their extensive application in flame retardants and plasticizers. Despite their widespread presence, the intricacies of OPE bioaccumulation within aquatic ecosystems remain poorly understood, particularly the environmental determinants influencing their distribution and the bioaccumulation dynamics across aquatic food chains. Here we show that water temperature plays a crucial role in modulating the dispersion of OPE in the aquatic environment of Poyang Lake. We quantified OPE concentrations across various matrices, uncovering levels ranging from 0.198 to 912.622 ng L-1 in water, 0.013-493.36 ng per g dry weight (dw) in sediment, 0.026-41.92 ng per g wet weight (ww) in plankton, 0.13-2100.72 ng per g dw in benthic invertebrates, and 0.31-3956.49 ng per g dw in wild fish, highlighting a pronounced bioaccumulation gradient. Notably, the intestines emerged as the principal site for OPE absorption, displaying the highest concentrations among the seven tissues examined. Among the various OPEs, tris(chloroethyl) phosphate was distinguished by its significant bioaccumulation potential within the aquatic food web, suggesting a need for heightened scrutiny. The propensity for OPE accumulation was markedly higher in benthic invertebrates than wild fish, indicating a differential vulnerability within aquatic biota. This study lays a foundational basis for the risk assessment of OPEs as emerging contaminants and underscores the imperative to prioritize the examination of bioaccumulation effects, particularly in benthic invertebrates, to inform future environmental safeguarding strategies.

GANSamples-ac4C: Enhancing ac4C site prediction via generative adversarial networks and transfer learning.

RNA modification, N4-acetylcytidine (ac4C), is enzymatically catalyzed by N-acetyltransferase 10 (NAT10) and plays an essential role across tRNA, rRNA, and mRNA. It influences various cellular functions, including mRNA stability and rRNA biosynthesis. Wet-lab detection of ac4C modification sites is highly resource-intensive and costly. Therefore, various machine learning and deep learning techniques have been employed for computational detection of ac4C modification sites. The known ac4C modification sites are limited for training an accurate and stable prediction model. This study introduces GANSamples-ac4C, a novel framework that synergizes transfer learning and generative adversarial network (GAN) to generate synthetic RNA sequences to train a better ac4C modification site prediction model. Comparative analysis reveals that GANSamples-ac4C outperforms existing state-of-the-art methods in identifying ac4C sites. Moreover, our result underscores the potential of synthetic data in mitigating the issue of data scarcity for biological sequence prediction tasks. Another major advantage of GANSamples-ac4C is its interpretable decision logic. Multi-faceted interpretability analyses detect key regions in the ac4C sequences influencing the discriminating decision between positive and negative samples, a pronounced enrichment of G in this region, and ac4C-associated motifs. These findings may offer novel insights for ac4C research. The GANSamples-ac4C framework and its source code are publicly accessible at http://www.healthinformaticslab.org/supp/.

[Effect of No-tillage on Soil Aggregates in Farmland：A Meta Analysis].

In order to clarify the impact of no-tillage on the quality of farmland soil aggregates in China and promote the adaptive application of no-tillage practices， a Meta-analysis was conducted by collecting data from 116 published studies. The effects of no-tillage on aggregate size distribution， mean weight diameter （MWD）， and aggregate-associated C were studied. The results showed that compared with that under tillage， no-tillage significantly increased the proportion of macroaggregates （10.9%） and MWD （12.8%） and decreased the proportion of clay and silt （-15.5%） but had no significant effect on soil microaggregate and aggregate-associated C. The subgroup and Meta regression analysis showed that no-tillage significantly increased the proportion of macroaggregates in Northwest China （17.6%） and MWD in North China （15.4%）. In upland and clay loam， no-tillage increased MWD by 12.6% and 18.4%， respectively. The effect of no-tillage on increasing the proportion of macroaggregates increased with the soil pH. When straw returned， no-tillage significantly increased the proportion of macroaggregates （9.6%） and MWD （11.6%）， but no significant effect of no-tillage on aggregates was found after straw removal. Regarding test duration， short-term （ < 5 a） no-tillage could significantly increase the proportion of macroaggregates， whereas long-term （ > 10 a） no-tillage could improve the MWD. In different soil layers， no-tillage could only significantly improve the aggregate size distribution and MWD in topsoil （0-20 cm） but had no effect in subsoil （ > 20 cm）. In summary， no-tillage could improve aggregate size distribution and stability but had no effect on aggregate-associated C. Production region， soil properties， field management methods， and other factors should be fully considered in production practice to effectively improve the quality of soil aggregates.

Fish Physiologically Based Toxicokinetic Modeling Approach for In Vitro-In Vivo and Cross-Species Extrapolation of Endocrine-Disrupting Chemicals in Risk Assessment.

High-throughput in vitro assays combined with in vitro-in vivo extrapolation (IVIVE) leverage in vitro responses to predict the corresponding in vivo exposures and thresholds of concern. The integrated approach is also expected to offer the potential for efficient tools to provide estimates of chemical toxicity to various wildlife species instead of animal testing. However, developing fish physiologically based toxicokinetic (PBTK) models for IVIVE in ecological applications is challenging, especially for plausible estimation of an internal effective dose, such as fish equivalent concentration (FEC). Here, a fish PBTK model linked with the IVIVE approach was established, with parameter optimization of chemical unbound fraction, pH-dependent ionization and hepatic clearance, and integration of temperature effect and growth dilution. The fish PBTK-IVIVE approach provides not only a more precise estimation of tissue-specific concentrations but also a reasonable approximation of FEC targeting the estrogenic potency of endocrine-disrupting chemicals. Both predictions were compared with in vivo data and were accurate for most indissociable/dissociable chemicals. Furthermore, the model can help determine cross-species variability and sensitivity among the five fish species. Using the available IVIVE-derived FEC with target pathways is helpful to develop predicted no-effect concentration for chemicals with similar mode of action and support screening-level ecological risk assessment.

Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway?

Organophosphorus flame retardants (OPFRs) have been frequently detected with relatively high concentrations in various environmental media and are considered emerging environmental pollutants. However, their biological effect and underlying mechanism is still unclear, and whether chlorinated OPFRs (Cl-OPFRs) cause adverse outcomes with the same molecular initial events or share the same key events (KEs) remains unknown. In this study, in vitro bioassays were conducted to analyze the cytotoxicity, mitochondrial impairment, DNA damage and molecular mechanisms of two Cl-OPFRs. The results showed that these two Cl-OPFRs, which have similar structures, induced severe cellular and molecular damages via different underlying mechanisms. Both tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) (TCPP) induced oxidative stress-mediated mitochondrial impairment and DNA damage, as shown by the overproduction of intracellular reactive oxygen species (ROS) and mitochondrial superoxide. Furthermore, the DNA damage caused by TCPP resulted in p53/p21-mediated cell cycle arrest, as evidenced by flow cytometry and real-time PCR. At the cellular and molecular levels, TCPP increased the sub-G1 apoptotic peak and upregulated the p53/Bax apoptosis pathway, possibly resulted in apoptosis associated with its stronger cytotoxicity. Although structurally similar to TCPP, TCEP did not induce mitochondrial impairment and DNA damage by the same KEs. These results provide insight into the toxicity of Cl-OPFRs with similar structures but different mechanisms, which is of great significance for constructing adverse outcome pathways or determining intermediate KEs.

Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.

Background: More than 850 million people worldwide suffer from acute and chronic kidney diseases (CKD) which are tremendous socioeconomic burdens for society. Currently, the treatment choices for CKD are limited. There is a great need to understand the underlying mechanisms of the development of CKD in order to develop potential therapeutic strategies. Summary: The alteration in cellular metabolism has emerged as an important common pathological mechanism in different kidney diseases. Metabolic intervening and reprogramming will yield new insights to prevent and slow the progression of kidney disease. As one essential component of cellular metabolisms in fuel-source preferences (glucose, fatty acids, or ketones), the polyamine compound metabolism comprising the metabolites (spermine, spermidine, and putrescine) and their biosynthetic and catabolic enzymes are an endogenous pathophysiological regulator that is arising as a potential therapeutic object for many diseases. Key Messages: This article aimed to review current knowledge on polyamine metabolism and physiological processes, and its potential regulatory and beneficial roles in immunoregulation, mitochondrial homeostasis, autophagy, DNA damage, and kidney diseases, and thus provide a novel therapeutic opportunity for kidney diseases.

Kaposiform hemangioendothelioma presented with raynaud phenomenon: a case report.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm affecting infants or young children. KHE includes a spectrum of lesions, ranging from small and superficial tumors to large and invasive lesions with Kasabach-Merritt phenomenon (KMP). Currently, no published studies have reported a KHE presenting as thrombocytopenia and Raynaud phenomenon. CASE PRESENTATION: A 2-year-old boy with right hand swelling and thrombocytopenia was admitted to our hospital. His right hand turned swelling and red, even occasionally cyanotic. This condition became worse in response to cool environments and improved with warming, and platelet counts were between 50 ~ 80 × 10^9/L. Physical examination on admission revealed the swelling and frostbite-like rash of the right-hand fingers, and the skin temperature of the right hand was lower than the left. On day 3 of admission, chest CT results showed an irregular mass on the right side of the spine. The puncture biopsy demonstrated positive CD31, D2-40, and FLI1 immunohistochemical staining, but negative GLUT1 staining, confirming the diagnosis of KHE. Furthermore, endothelin-1 (ET1) expression levels significantly increased, and eNOS and A20 expression levels significantly decreased comparing with control patients. The patient received methylprednisolone and sirolimus treatments, and his condition gradually improved during the follow-up. CONCLUSIONS: We reported the first case of KHE presenting with thrombocytopenia and Raynaud phenomenon. The development of Raynaud phenomenon could be associated with increased ET-1 and reduced eNOS and A20 expressions. Careful differential diagnosis of hidden KHE should be considered in children with thrombocytopenia and Raynaud phenomenon.

Self-healing properties of symmetrical power-exponent-phase vortices.

The self-healing properties of symmetrical power-exponent-phase vortices (SPEPVs) are analyzed in this paper. By placing an obstacle in the optical path of SPEPVs, we simulated the propagation of the obstructed SPEPVs and verified the self-healing of the beam theoretically. We also explored the influence of external factors (e.g., obstacle size and position) and internal parameters (topological charge l and power exponent n) on the self-healing effect of obstructed SPEPVs. Furthermore, the energy flow density, similarity coefficient, effective self-healing distance, and diffraction efficiency of the obstructed SPEPVs were also discussed. The results demonstrated that the transverse energy flows around the obstructed region of SPEPVs will recover with the propagation distance increased, and the effective self-healing distance gradually increases linearly with the obstacle size r x increased. The self-healing characteristic gives the petal-like SPEPVs the ability to trap microparticles three-dimensionally.

Performance of interferon-gamma levels may lead to earlier diagnosing macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of rheumatic diseases, predominantly in systemic juvenile idiopathic arthritis (SJIA), and is considered as an autoinflammatory disease. Specific cytokine profiles could play a pivotal role in this inflammatory response. Gram-negative bacteremia, bacterial pneumonia, Kawasaki disease, and active SJIA exhibited similar cytokine profiles with elevated interleukin-6 (IL-6) and/or IL-10, further suggesting a correlation between them. Only when JIA is complicated by MAS can increased interferon-γ (IFN-γ) levels be observed. Therefore, increased serum IFN-γ levels could contribute to early diagnosing MAS in patients with SJIA in combination with other variables such as serum ferritin. A prospective multi-center study will be performed to further confirm the role of IFN-γ in the early recognition of MAS in SJIA.

Systemic Immune-Inflammation Index Was Significantly Associated with All-Cause and Cardiovascular-Specific Mortalities in Patients Receiving Peritoneal Dialysis.

Purpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD. Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet count×neutrophil count/lymphocyte count. Kaplan-Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities. Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088-1.327, P<0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126-1.456, P<0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066-1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185-2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only. Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.

Multi-helix beams generated with binary helico-conical phase patterns.

In this paper, we generate a type of double helico-conical beam (HCB) by binarizing the modified helico-conical phase (MHCP). The diffraction patterns of the double HCBs were analyzed theoretically and experimentally. The relative position of the double HCBs can be adjusted arbitrarily by introducing a blazed grating only. In addition, the superposition of multiple binary MHCPs can be used to generate multi-helix beams. Accordingly, the diffraction patterns of the multi-helix beams were also analyzed theoretically and experimentally. The results demonstrated that the number and relative position of multi-helix beams can be adjusted by the number of superimposed MHCP profiles and the azimuth factor θ j, respectively. This kind of arrayed HCB will be potentially applied in the fields of optical manipulation and multiplexed holography.

In vitro to in vivo extrapolation for predicting human equivalent dose of phenolic endocrine disrupting chemicals: PBTK model development, biological pathways, outcomes and performance.

In vitro to in vivo (IVIVE) leverages in vitro high-throughput biological responses to predict the corresponding in vivo exposures and further estimate the human safe dose. However, for phenolic endocrine disrupting chemicals (EDCs) linked with complicated biological pathways and adverse outcomes (AO), such as bisphenol A (BPA) and 4-nonylphenol (4-NP), plausible estimation of human equivalent doses (HED) by IVIVE approaches considering various biological pathways and endpoints is still challenging. To explore the capabilities and limitations of IVIVE, this study conducted physiologically based toxicokinetic (PBTK)-IVIVE approaches to derive pathway-specific HEDs using BPA and 4-NP as examples. In vitro HEDs of BPA and 4-NP varied in different adverse outcomes, pathways, and testing endpoints and ranged from 0.0013 to 1.0986 mg/kg bw/day and 0.0551 to 1.7483 mg/kg bw/day, respectively. In vitro HEDs associated with reproductive AOs initiated by PPARα activation and ER agonism were the most sensitive. Model verification suggested the potential of using effective in vitro data to determine reasonable approximation of in vivo HEDs for the same AO (fold differences of most AOs ranged in 0.14-2.74 and better predictions for apical endpoints). Furthermore, system-specific parameters of cardiac output and its fraction, body weight, as well as chemical-specific parameters of partition coefficient and liver metabolic were most sensitive for the PBTK simulations. The results indicated that the application of fit for-purpose PBTK-IVIVE approach could provide credible pathway-specific HEDs and contribute to high throughput prioritization of chemicals in a more realistic scenario.

Photo-induced energy transfer within donor-acceptor dipeptides: Towards an artificial light-harvesting hydrogel system.

Well-defined relative orientations and distances between chromophores are prerequisites for high-efficiency energy transfer, which can generally be realized by regularly assembling short peptide compounds with different absorption wavelengths and luminescence positions. Herein, a series of dipeptides are designed and synthesized, where the dipeptides contain different chromophores with several absorption bands. A co-self-assembled peptide hydrogel is prepared for artificial light-harvesting systems. The photophysical properties and assembly behavior of these dipeptide-chromophore conjugates in solution and hydrogel are systematically studied. As a result of the three-dimensional (3-D) self-assembly feature, effective energy transfer between donor and acceptor in the hydrogel system is achieved. These systems exhibit high antenna effect at a high donor/acceptor ratio (2564:1), which is characterized by an increase in the fluorescence intensity. Further, multiple molecules with different absorption wavelengths can be co-assembled as energy donors in order to achieve a wide spectrum of absorption. The method allows flexible light-harvesting systems to be realized. The ratio of energy donors to acceptors can be adjusted arbitrarily, and constructive motifs can be selected based on the application.

Case report: Aggressive progression of acute heart failure due to juvenile tuberculosis-associated Takayasu arteritis with aortic stenosis and thrombosis.

Background: Takayasu arteritis (TA) is a chronic granulomatous vasculitis with unknown pathophysiology. TA with severe aortic obstruction has a poor prognosis. However, the efficacy of biologics and appropriate timing of surgical intervention remain controversial. We report a case of tuberculosis (TB)-associated TA with aggressive acute heart failure (AHF), pulmonary hypertension (PH), thrombosis, and seizure, who failed to survive after surgery. Case presentation: A 10-year-old boy who developed a cough with chest tightness, shortness of breath, hemoptysis with reduced left ventricular ejection fraction, PH, and increased C-reactive protein and erythrocyte sedimentation rate was hospitalized at the pediatric intensive care unit of our hospital. He had strongly positive purified protein derivative skin test and interferon-gamma release assay result. Computed tomography angiography (CTA) showed occlusion of proximal left subclavian artery and stenosis of descending aorta and upper abdominal aorta. His condition did not improve after administration of milrinone, diuretics, antihypertensive agents, and intravenous methylprednisolone pulse followed by oral prednisone. Intravenous tocilizumab was administered for five doses, followed by two doses of infliximab, but his HF worsened, and CTA on day 77 showed complete occlusion of the descending aorta with large thrombus. He had a seizure on day 99 with deterioration of renal function. Balloon angioplasty and catheter-directed thrombolysis were performed on day 127. Unfortunately, the child's heart function continued to deteriorate and died on day 133. Conclusion: TB infection may be related to juvenile TA. The biologics, thrombolysis, and surgical intervention failed to achieve the anticipated effect in our case with aggressive AHF due to severe aortic stenosis and thrombosis. More studies are needed to determine the role of biologics and surgery in such dire cases.

Interaction effect between fasting plasma glucose and lipid profiles on mortality of peritoneal dialysis patients.

Background: Peritoneal dialysis (PD) patients have a high risk of abnormal glucose and lipids metabolism. Objective: We investigated the effects of baseline fasting plasma glucose (FPG) as well as its interaction with lipid profiles on all-cause and cardiovascular disease (CVD) cause-specific mortality in PD patients. Methods: A total of 1995 PD patients were enrolled. Kaplan-Meier survival curves and Cox regression models were performed to assess the association of FPG levels with mortality in PD patients. Results: During a median (25th-75th quartile) follow-up period of 48.1 (21.8-77.9) months, 567 (28.4%) patients died, including 282 (14.1%) CVD deaths. Kaplan-Meier survival curves showed that all-cause and CVD cause-specific mortality increased significantly with elevated baseline FPG levels (Log-rank tests: both P-values <.001). However, with adjustment for potential confounding factors, baseline FPG levels were not significantly associated with all-cause and CVD cause-specific mortality. Nevertheless, a significant interaction between baseline FPG and low-density lipoprotein cholesterol (LDL-C) on all-cause mortality was found (P for interaction test: .013), and subgroup analyses further showed that all-cause mortality was significantly increased for baseline FPG ≥7.0 mmol/L compared with the normal reference (FPG <5.6 mmol/L) (hazard ratio 1.89, 95% confidence interval 1.11-3.23, P-value = .020) for patients with LDL-C ≥3.37 mmol/L only, but not for those with lower LDL-C levels (<3.37 mmol/L). Conclusion: The significant interaction effect between baseline FPG and LDL-C on all-cause mortality showed that, for PD patients with LDL-C ≥3.37 mmol/L, higher FPG levels (≥7.0 mmol/L) were significantly associated with an increased risk of all-cause mortality and need more intensive management of their FPG by clinicians in the future.

MicroRNA-146a Improved Acute Lung Injury Induced by hepatic Ischemia-reperfusion Injury by Inhibiting PRDX1.

Hepatic ischemia-reperfusion injury (HIRI)-induced acute lung injury (ALI) is characterized by high incidence and poor prognosis. The regulatory role of microRNA-146a (miR-146a) in HIRI has been reported, but if miR-146a could affect the progression of HIRI-induced ALI has not been reported. The mice HIRI model was established by ligating left hepatic portal vein and hepatic artery for 60 minutes and then treating with reperfusion for 4 hours. Hypoxia-reoxygenation (HR) was performed to establish cell model. The binding site between miR-146a and Peroxidase 1 (PRDX1) was predicted and validated. The levels of inflammation factors and redox markers were detected with commercial kits. Significant lower expression of miR-146a and higher expression of PRDX1 in HIRI animal model were observed. miR-146a inhibited the liver injury after HIRI induction through targeting PRDX1. miR-146a inhibited the lung injury caused by HIRI via regulating PRDX1. The inhibition of cell apoptosis and inflammation factors by miR-146a were reversed by pcDNA-PRDX1. This research demonstrated that miR-146a improved ALI caused by HIRI by inhibiting apoptosis, inflammation, oxidative condition through targeting PRDX1. This study might provide a novel thought for the prevention and treatment of ALI caused by HIRI by regulating miR-146a/PRDX1 axis.

First metabolic profiling of 4-n-nonylphenol in human liver microsomes by integrated approaches to testing and assessment: Metabolites, pathways, and biological effects.

4-n-nonylphenol (4-n-NP), a typical endocrine disrupting chemical, has been so far frequently detected in various environmental mediums and editable food. However, the specific metabolic pathways in human and potential adverse effects of metabolites have not been elucidated yet. Here, metabolic profiling of 4-n-NP in human liver microsome (HLM) was comprehensively characterized by integrated approaches of testing and assessment. A total of 21 metabolites were identified using nontarget analysis with high-resolution mass spectrum, including three groups of unique phase I metabolites first determined in HLM. Seven various metabolic pathways of 4-n-NP were identified by both in silico and in vitro, and CYP1A2, 2C19, and 2D6 were the mainly participating enzymes. Two secondary metabolites with carbonyl groups on side chains (M4, M7) presented most abundant in HLM, which were also predicted to have high binding affinities towards HPG-axis-related receptors (AR, ER, and PR). ESRs (estrogen receptors) were shared core protein targets for all metabolites revealed by protein-protein interaction networks. Biological functions enrichment analysis indicated that 4-n-NP metabolites might primarily involve in ESR-mediated signaling, GPCR ligand binding, Class A/1 (Rhodopsin-like receptors) and metabolism-related pathways. These findings of 4-n-NP metabolites, pathways, and biological effects provide insightful information for its environmental exposure and risk assessment.

Passive sampling of diverse pesticides in water by hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane: Kinetics, equilibrium partitioning and field application.

Pesticides are useful products for agriculture and human life, but they are often released into surface waters and are hazardous to aquatic ecosystems. Pesticides monitoring in surface waters is challenging due to the great variety, ultratrace levels and nonpoint source pollution of pesticides; however, continuous passive sampling may be conducive to solving these problems. This work evaluated the performance of a newly developed passive sampler (hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane, HECAM) for six types of currently used/present pesticides. The uptake kinetics and equilibrium partitioning of nineteen pesticides in different dissolved concentrations were studied by dynamic accumulation and equilibrium partitioning experiments, respectively. In the dynamic accumulation experiments, pesticides gradually accumulated in the HECAM and followed a first-order kinetic model. The same type of pesticides had roughly comparable accumulation concentrations. The estimated uptake rate constants ranged from 1.04 to 13.5 L g-1 d-1, and sampling rates ranged from 0.02 to 0.31 L d-1 for the pesticides in the HECAM (size of 2 cm × 3 cm). Pesticide accumulation concentrations in the HECAM increased linearly with increasing dissolved concentrations, which means that varying concentrations can also be monitored by the HECAM. In the equilibrium partitioning experiments, the pesticide partitioning behavior at varying dissolved concentrations can be described by the Freundlich model. The calculated equilibrium partition coefficients (log KD) for pesticides ranged from 3.32 to 4.54, and different pesticide types showed different changes with log Kow. Comparable results were found when estimating chemical equilibrium partition coefficients by the dynamic accumulation and equilibrium partitioning methods. Field deployment of the HECAM in river waters resulted in the detection of four pesticides, and the measured results were comparable to those of active sampling coupled with liquid-liquid extraction. These results suggest that the HECAM would be a promising strategy for simultaneously monitoring diverse pesticides in waters.

Polarization-sensitive multi-frequency switches and high-performance slow light based on quadruple plasmon-induced transparency in a patterned graphene-based terahertz metamaterial.

A periodic patterned graphene-based terahertz metamaterial comprising three transverse graphene strips and one longitudinal continuous graphene ribbon is proposed to achieve a dynamically tunable quadruple plasmon-induced transparency (PIT) effect. Further analysis of the magnetic field distribution along the x-direction shows that the quadruple-PIT window can be produced by the strong destructive interference between the bright mode and the dark mode. The spectral response characteristics of the quadruple-PIT effect are numerically and theoretically investigated, and the results obtained by the finite-difference time-domain (FDTD) simulation fit well with that by the coupled mode theory (CMT) calculation. In addition, two hepta-frequency asynchronous switches are achieved by tuning the Fermi energy of the graphene, and their maximum modulation depths are 98.9% and 99.7%, corresponding to the insertion losses of 0.173 dB and 0.334 dB, respectively. Further studies show that polarization light has a significant impact on the quadruple-PIT, resulting in a polarization-sensitive switch being realized with a maximum modulation depth of 99.7% and a minimum insertion loss of 0.048 dB. In addition, when the Fermi energy is equal to 1.2 eV, the maximum time delay and group refractive index of the quadruple-PIT can be respectively as high as 1.065 ps and 3194, and the maximum delay-bandwidth product reaches 1.098, which means that excellent optical storage is achieved. Thus, our proposed quadruple-PIT system can be used to design a terahertz multi-channel switch and optical storage.