Dicarboxylic acids are important constituents of organic aerosols, but the lack of their seasonal and vertical distribution hinders thorough knowledge of atmospheric physicochemical behavior. This study examines dicarboxylic acids at three heights (similar to 3, 118, and 488 m) on the 600 m high Canton Tower in urban Guangzhou, aiming to illustrate their primary sources and formation pathways across different seasons and heights. The concentration of dicarboxylic acids (678.7 +/- 351.9 ng m(-3)) was lower or comparable to those in domestic cities but higher than in remote aeras. Oxalic acid had the highest concentration, with malonic, succinic, glyoxylic, and azelaic acids following. Most dicarboxylic acids peaked in autumn, following by winter, spring and summer. Higher dicarboxylic acids were observed at upper layers. The C-3/C-4 (1.5 +/- 0.5) was relatively higher, and the proportion of C-2 in dicarboxylic acids increased with height. Our results showed that combustion and secondary conversion were primary sources of dicarboxylic acids in dry season, while biomass combustion and secondary formation processes dominated during wet season. Significant gas-phase oxidations were prevalent during summer, while aqueous-phase formations were prominent in spring. Aerosol aging process played an important role at higher atmospheric levels throughout the year, suggesting an enhanced atmospheric oxidation capacity in upper boundary layers. These vertical profiling measurements enable the identification of predominant origins and formation pathways of dicarboxylic acids across different seasons and boundary layer dynamics. The findings provide critical insights for understanding atmospheric chemical evolution processes, validating atmospheric models, and developing effective air pollution mitigation strategies.

Secondary aerosols are a major component of atmospheric particulate matter, but their formation pathways under different conditions in high mountains remain incompletely understood, impeding accurate assessment of their environmental and climatic impacts. In this study, the physicochemical properties and formation mechanisms of secondary aerosols in cloud‐free, cloud interstitial, and cloud residual particles are investigated at a mountain site in southeastern China. The results show that elevated concentrations of NO 3 − and more‐oxidized oxygenated organic aerosol (MO‐OOA) in cloud‐free particles primarily result from aqueous‐phase reactions along the dust transport. Aqueous‐phase processes during cloud events promoted the formation of NO 3 − , SO 4 2− , NH 4 + and MO‐OOA, with cloud residual particles exhibited 1.2–1.6 times higher growth rates than cloud interstitial particles. Lower fractions of C 4 H 7 + , C 4 H 9 + , C 5 H 6 O + , and C 3 H 7 O 3 + were found in cloud residual particles, suggesting that cloud droplets could facilitate the aging of these organics. Additionally, higher liquid water content increases the O/C ratio in secondary organic aerosols (SOA) by 0.1–0.15, and higher O 3 concentrations facilitate oxidation in cloud droplets via hydroxyl radicals (•OH) production in the acidic cloud water. SOA in cloud residual particles was enriched with carbonyl functional groups (>C=O), suggesting the presence of oxidized acids or esters, which contrasted with less‐oxidized aldehydes/ketones in cloud‐free and cloud interstitial particles. These findings highlight the combined influence of long‐range transport and cloud processing on secondary aerosol chemistry in high mountain region in southeastern China and provide critical insights for improving aerosol‐climate models in topographically complex regions.

Secondary organic aerosol (SOA) accounts for a large fraction of fine particulate matter (PM2.5), but the lack of vertical observations of SOA in the urban boundary layer (UBL) limits a comprehensive understanding of its sources and formation mechanisms. In this study, PM2.5 samples were simultaneously collected at 3 m, 118 m, and 488 m on the Canton Tower in Guangzhou during winter. Typical SOA tracers, including oxidation products of isoprene (SOAI), monoterpene (SOAM), sesquiterpene (SOAS), and toluene (ASOA), were investigated alongside meteorological parameters and gaseous/particulate pollutants. Total concentrations of SOA tracers showed an increasing trend with height, with daytime levels exceeding nighttime levels. C5-alkene triols and 2-methylglyceric acid displayed a significant increase with height, potentially affected by nighttime chemistry in the residual layer, determining the overall vertical trend of SOAI tracers. Concentrations of later-generation SOAM (SOAM_S) tracers also increased with height, while those of first-generation SOAM (SOAM_F) tracers decreased, indicating relatively aged SOAM in the upper layers. SOAS and ASOA tracers exhibited higher enhancement under polluted conditions, likely impacted by biomass burning and anthropogenic emissions. The yields of SOAI tracers varied with temperature in the vertical profile. The formation of SOAM_F tracers was negatively correlated with relative humidity, liquid water content, and pH, affecting their vertical distributions. The effect of O3 on SOA formation enhanced significantly with height, influenced by air mass transport, and likely contributed to the higher yields of SOA in the upper layer. However, at ground level, SOA formation was primarily driven by high local emissions of both NOx and volatile organic compounds. We also observed the roles of SO2 in SOA generation, particularly at 118 m. This study demonstrates the vertical diurnal characteristics of SOA tracers in the UBL, highlighting the varying effects of meteorological conditions and anthropogenic pollutants on SOA formation at different heights.

Nitrous acid (HONO) is an important source of atmospheric hydroxyl radical (OH). However, HONO abundance in the marine boundary layer remain largely unknown. Here, ship-based measurements were performed to characterize the origins of HONO from ship plumes, marine atmosphere, and continental emissions over South China Sea (SCS) during September 2021. The results showed that the HONO concentrations were measured at substantial levels (1.0 ± 0.8 ppbv) in polluted plumes due to generally high NOx concentrations (52.3 ± 52.5 ppbv). Comparably, much lower HONO concentrations (0.086 ± 0.102 ppbv) were observed for marine atmosphere. During nighttime, the heterogeneous conversion of NO2 was the predominant source of HONO and occurred mainly on the sea surfaces through NO2 deposition. The HONO yield from this deposition (the proportion of NO2 that was converted to HONO) was 0.08 and 0.06 for the marine atmosphere and continental emissions, respectively. In contrast, daytime known HONO formation of marine atmospheric origins was mainly attributed to homogeneous OH + NO reaction, although the contribution of heterogeneous NO2 conversion might not be negligible. Approximately half of HONO sources during daytime are unknown, which were likely from photo-enhanced NO2 conversation on the sea surfaces. Our results showed that for marine atmosphere and ship plumes, the daily contributions of HONO photolysis to OH radical formation were about 20.8 % and 72.2 %, respectively, while the contributions from ozone photolysis were 79.2 % and 27.8 %. An average HONO concentration of 0.17 ppbv was measured in close shore regions when air masses originated from mainland China, with the contributions from HONO and ozone to OH radical of 21.4 % and 78.6 % respectively, similar to those for the marine atmosphere. This study suggests that HONO in the SCS has various sources (e.g., marine atmosphere, ship plumes, and continental emissions) and makes significant contributions to the OH abundance which affects the oxidation capacity in this area.

Background:The lifestyles of preschoolers have become physically inactive and sedentary, their eating habits unhealthy, and their sleep routines increasingly disturbed. Parental involvement appears crucial to combat the unhealthy lifestyle of preschoolers. Because of the recognized barriers to traditional face-to-face interventions, easy access and lower costs make electronic health (eHealth) interventions appealing. However, whether parent-based eHealth intervention may be harnessed to improve the aforementioned lifestyle behaviors of preschoolers is currently unclear, a gap that this systematic review intends to address. This study aims to systematically review the current literature concerning the effectiveness of parent-based eHealth intervention on the physical activity, dietary behaviors, and sleep of preschoolers.Method:This systematic review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Six databases (EMBASE, PubMed, MEDLINE, Web of Science, SPORTDiscus, and PsycINFO) were retrieved for the period from January 2000 to December 2022. Studies were eligible if 1 they were quantitative study design; 2 eHealth interventions in which parents were the change agents targeted children aged 3-6 years; 3 interventions examined the effectiveness of eHealth or incorporated eHealth as one of the intervention modalities; 4 at least one variable included in either primary or secondary outcome had to concentrate on the physical activity, diet, and sleep of preschoolers; 5 publication type was limited to the English language and peer-reviewed journal articles; 6 study settings were confined to family- or parent-based ones. The risk of bias was assessed, based upon Version 2 of the Cochrane risk-of-tool for randomized trials (RoB2).Results:Twelve studies were screened. No significant group-by-time improvement in physical activity was found in studies related to physical activity outcomes. Two studies reported a significant difference between groups concerning motor ability, with one study indicating improved object control with the other reporting improvement in both object control and locomotor skills. Of the studies related to dietary behavior outcomes, six studies reported a significant difference at the posttest compared to the control group, in terms of vegetable and fruit intake, sugar-sweetened drinks, reduced candy consumption, and improved non-core food. Three studies reported a significant difference between groups in sleep duration at the end of the posttest, with the result of one study limited to preference-only participants. None of the reviewed studies found a significant difference between groups for sleep problems.Conclusion:Parent-based eHealth interventions were not significantly effective in improving physical activity and reducing sleep problems in preschoolers, but the majority of studies have found that this type of intervention significantly improves the dietary behaviors and sleep duration of preschoolers. High-quality, robustly designed studies to balance the intervention dosage and sequence are needed to investigate the effectiveness of parent-based eHealth intervention on physical activity, dietary behaviors, and sleep in preschoolers, particularly those raised in other cultural background, which may significantly impact their lifestyle.Trial registration:International Prospective Register of Systematic Review (PROSPERO): CRD42023418861.

Vascular calcification (VC) is recognized as a crucial risk factor for cardiovascular diseases. Our previous report revealed that the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) plays a role in this process. However, the underlying molecular mechanisms remain elusive. Notably, receptor-interacting protein kinase 1 (RIPK1) has been implicated in the development of cardiovascular diseases, yet its role and mechanisms in VC remain unexplored. To address this gap, we established models using chronic kidney disease mice and calcifying VSMCs to investigate the impact of RIPK1 on VC. Subsequently, a RIPK1-specific inhibitor (NEC-1) was applied in both in vitro and in vivo models. Our findings indicate significant activation of RIPK1 in calcified human arterial tissue, as well as in animal and cellular models. RIPK1 activation promotes the osteogenic transdifferentiation of VSMCs. Treatment with the NEC-1 substantially reduced VC. These results demonstrate that RIPK1 is a target for preventing VC.

The emergence of plasmid-mediated colistin resistance threatens the efficacy of colistin as a last-resort antibiotic used to treat infection caused by Gram-negative bacteria (GNB). Given the shortage of new antibiotics, the discovery of adjuvants to existing antibiotics is a promising strategy to combat infections caused by multidrug-resistant (MDR) GNB. This study was designed to investigate the potential synergistic antibacterial activity of bavachin, a bioactive compound extracted from the Psoralea Fructus, combined with colistin against MDR GNB. Herein, the synergistic efficacy in vitro and the therapeutic efficacy of colistin combined with bavachin in vivo were evaluated. The synergistic mechanism was detected by fluorescent probe and the transcript levels of mcr-1. Bavachin combined with colistin showed an excellent synergistic activity against GNB, as the FICI ≤ 0.5. In contrast to colistin alone, combination therapy dramatically increased the survival rate of Galleria mellonella and mice in vivo. Moreover, the combination of bavachin and colistin significantly reduced the amount of bacterial biofilm formation, improved the membrane disruption of colistin and inhibited mcr-1 transcription. These findings show that bavachin is a potential adjuvant of colistin, which may provide a new strategy to combat colistin-resistant bacteria infection with lower doses of colistin.

Background: No study has validated, compared and adapted scoring systems for prognosis prediction based on donor kidney core biopsy (CB), with less glomeruli than wedge biopsy. Methods: A total of 185 donor kidney CB specimens were reviewed using seven scoring systems. The association between the total score, item scores, score-based grading, and allograft prognosis was investigated. In specimens with less than ten glomeruli (88/185, 47.6%), scoring systems were modified by adjusting weights of the item scores. Results: The Maryland aggregate pathology index (MAPI) score-based grading and periglomerular fibrosis (PGF) associated with delayed graft function (DGF) (Grade: OR = 1.59, p < 0.001; PGF: OR = 1.06, p = 0.006). Total score, score-based grading and chronic lesion score in scoring systems associated with one-year and 3-year eGFR after transplantation. Total-score-based models had similar predictive capacities for eGFR in all scoring systems, except MAPI and Ugarte. Score of glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), and arteriolar hyalinosis (AH) had good eGFR predictive capacities. In specimens with less than ten glomeruli, modified scoring systems had better eGFR predictive capacities than original scoring systems. Conclusions: Scoring systems could predict allograft prognosis in paraffin-embedded CB with ten more glomeruli. A simple and pragmatic scoring system should include GS, IF, TA and AH, with weights assigned based on predictive capacity for prognosis. Replacing GS scores with tubulointerstitial scores could significantly improve the predictive capacity of eGFR. The conclusion should be further validated in frozen section.

Background/purpose: The guided protocols always yield a higher accuracy than freehand surgery. However, the accuracy of digital guides for crown lengthening surgery (CLS) is unknown. The purpose of this study was to evaluate the trueness of 3 types of digital guides for CLS. Materials and methods: Twenty individually designed maxillary models were divided into 4 groups according to surgical guides: type I (T1), type II (T2), type III (T3), and free-hand. T1 comprised a planed gingival margin at the tissue level. T2 included both the planed gingival margin and alveolar crest at the tissue level. T3 consisted of a planed gingival margin at the tissue level and an alveolar crest at the bone level. CLS was performed under the indication of the guides. Trueness of the guides was evaluated through the deviation of the gingival zenith and alveolar crest height. Results: The control group had higher vertical and horizontal distance deviations of gingival zenith compared to the 3 digital guide groups (P < 0.001). There were no significant differences among the 3 test groups in terms of gingival zenith deviations (P > 0.05). With regard to height deviation of alveolar crest, the control and T1 groups were higher than T2 group (P < 0.001), while T3 group had the lowest deviations among the 4 groups (P < 0.001). Conclusion: The digital guides assisted CLS procedures are more accurate than free-hand method. The trueness of type III guide was better than type I and type II. (c) 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Phenolic aldehydes as brown carbon (BrC) chromophores may contribute to the mass of aqueous secondary organic aerosol (aqSOA) due to their potential as atmospheric photosensitizers. However, there is still a lack of knowledge about their sensitizing ability and the impact of environmental factors. In this work, we studied the photosensitized behavior of a phenolic aldehyde, syringaldehyde (SyrAld), in aqueous solutions. Under illumination, the influences of environmental factors such as precursor concentration, solution pH, codissolved inorganic constituents (NaCl and Na2SO4), and organic matter (vanillyl alcohol, VAL, a methoxyphenol produced during biomass burning) were investigated. Our results show that increasing pH and salt concentration causes a strong red shift in the absorption peak of SyrAld, and chloride salts and sulfate salts exert different effects on the photochemical reactivity of SyrAld. Interestingly, the opposite effects of SyrAld on VAL oxidation were observed at different wavelengths of light. Under UV-B irradiation, SyrAld inhibited VAL degradation by the light shielding effect, while under UV-A irradiation, photosensitization of SyrAld promoted VAL degradation. The major photooxidation products were identified as hydroxylated products induced by reactive oxygen species (OH radicals) and dimerized products by direct oxidation of triplet excited state SyrAld (3SyrAld*) using UPLC-Q-TOF-MS. This work suggests that environmental factors play significant roles in determining the fate of phenolic aldehydes in atmospheric waters.

Background:The rapid spread of bacteria with plasmid-mediated resistance to antibiotics poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue.Methods:Synergistic activity of the FDA-approved agent oxethazine combined with colistin was investigated in vitro using checkerboard assays and time-kill curves. The synergistic mechanisms of their combination of oxethazine and colistin was explored by fluorescent dye, scanning electron microscopy (SEM) and LC-MS/MS. The synergistic efficacy was evaluated in vivo by the Galleria mellonella and mouse sepsis models.Results:In this study, we found that oxethazine could effectively enhance the antibacterial activity of colistin against both mcr-positive and -negative pathogens, and mechanistic assays revealed that oxethazine could improve the ability of colistin to destruct bacterial outer membrane and cytoplasmic membrane permeability. In addition, their combination triggered the accumulation of reactive oxygen species causing additional damage to the membrane structure resulting in cell death. Furthermore, oxethazine significantly enhanced the therapeutic efficacy of colistin in two animal models.Conclusion:These results suggested that oxethazine, as a promising antibiotic adjuvant, can effectively enhance colistin activity, providing a potential strategy for treating multidrug-resistant bacteria.

Streptococcus suis, an encapsulated zoonotic pathogen, has been reported to cause a variety of infectious diseases, such as meningitis and streptococcal-toxic-shock-like syndrome. Increasing antimicrobial resistance has triggered the need for new treatments. In the present study, we found that isopropoxy benzene guanidine (IBG) significantly attenuated the effects caused by S. suis infection, in vivo and in vitro, by killing S. suis and reducing S. suis pathogenicity. Further studies showed that IBG disrupted the integrity of S. suis cell membranes and increased the permeability of S. suis cell membranes, leading to an imbalance in proton motive force and the accumulation of intracellular ATP. Meanwhile, IBG antagonized the hemolysis activity of suilysin and decreased the expression of Sly gene. In vivo, IBG improved the viability of S. suis SS3-infected mice by reducing tissue bacterial load. In conclusion, IBG is a promising compound for the treatment of S. suis infections, given its antibacterial and anti-hemolysis activity.

Streptococcus suis is an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance in S. suis, and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused by S. suis are urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine against S. suis. Floxuridine showed excessive antibacterial activity against S. suis both in vivo and in vitro; 4 × MIC of floxuridine could kill S. suis within 8 h in a time–kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes of S. suis. Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor against S. suis.

Secondary organic aerosols (SOAs) account for a largefractionof atmospheric fine particles, but the mechanisms of their formationand evolution processes remain unclear. In this study, a ground-basedcounterflow virtual impactor was used in combination with an onlinetime-of-flight aerosol chemical speciation monitor to investigatethe multiphase (gaseous and aqueous) oxidation processes and the SOAinfluencing factors during cloud events at a mountain site in southernChina. Our results showed that the clouds promoted the formation oflow-oxidized oxygenated organic aerosol (LO-OOA) and more-oxidizedoxygenated organic aerosol (MO-OOA). At night, ozone (O-3) and nitrate radicals (NO3 center dot) oxidized volatileorganic compounds (VOCs, mostly biogenic VOCs) to the precursors ofLO-OOA and were absorbed in the cloud droplets to form LO-OOA, whilethe hydroxyl radical (center dot OH) was the main oxidant for LO-OOAduring daytime. In the cloud droplets, LO-OOA was further oxidizedby center dot OH to form MO-OOA. We propose that isoprene can be oxidizedto form products in the gas phase and then absorbed by acidic clouddroplets to form 2-methylglyceric acid (2-MG), 2-MG-organosulfate,and 2-MG-organonitrate. This study improves our understanding of SOAformation, driven by multiphase oxidation during cloud events.

Abstract Study question Whether letrozole-stimulated protocol has advantages over hormone replacement therapy (HRT) in frozen embryo transfer in patients with polycystic ovary syndrome (PCOS)? Summary answer Letrozole-stimulated protocol is more suitable for endometrial preparation than HRT in patients with PCOS, which can increase the live birth rate and reduce pregnancy complications. What is known already The current routine endometrial preparation protocol for women with PCOS is HRT. However, HRT is expensive, and recent studies have found HRT may increase the risk of adverse maternal and neonatal complications such as hypertensive disorders of pregnancy. Letrozole induces mono-ovulatory and has no antiestrogenic effect, and has been found to increase live birth rate compared with clomiphene in fresh embryo cycles. However, Letrozole is rarely used in frozen embryo cycles. Whether letrozole-stimulated protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable is still lack of evidence. Study design, size, duration This is a retrospective cohort study involving all frozen embryo transfer cycles with letrozole-stimulated and HRT for PCOS during the period from August 2018 to December 2020 at a tertiary care center. Participants/materials, setting, methods A total of 2011 letrozole-stimulated cycles and 2211 HRT cycles were included in the analysis. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between letrozole-stimulated protocol and HRT after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which letrozole-stimulated protocol was suitable. Main results and the role of chance After adjusting for confounding, letrozole-stimulated protocol increased the clinical pregnancy rate (OR,1.44; 95%CI,1.21-1.70), live birth rate (OR,1.49; 95%CI,1.27-1.74) and reduced the incidence of miscarriage (OR, 0.71; 95%CI,0.55-0.92), hypertensive disorders of pregnancy (OR, 0.66; 95%CI,0.45,0.98), gestational diabetes mellitus (OR,0.75; 95%CI,0.57,0.98) and cesarean section (OR,0.78; 95%CI,0.61,0.99) than HRT. There were no significant differences in other outcomes such as preterm birth, small for gestational age, and large for gestational age between the two endometrial preparation protocols. Subgroup analysis according to maternal age, BMI, insulin resistance and PCOS classification showed that the live birth rate of letrozole-stimulated protocol was significantly higher than that of HRT in all subgroups. Limitations, reasons for caution This study is a retrospective study, the population characteristics of the two endometrial preparation protocols existed differences. Although multivariate logistic regression was used to adjust some factors, the interference of known and unknown factors on the outcomes cannot be completely avoided. Wider implications of the findings This retrospective study found letrozole-stimulated protocol has more advantages than HRT, which can improve the live birth rate and reduce the incidence of hypertensive disorders of pregnancy, gestational diabetes mellitus in patients with PCOS. High-quality well-powered randomised clinical trials and possible mechanistic studies are needed to further validate this conclusion. Trial registration number NA

The transport of dissolved carbon (DC) from inland waters to the ocean is an important component of the global carbon cycle. However, how water retention time (WRT) affects the concentration and flux of DC in inland waters remains unclear. In this study, we collected 613 data points for WRT, the concentration and flux of dissolved organic carbon (DOC), inorganic carbon (DIC) and dissolved CO 2 from 587 field studies and 26 model simulations worldwide. We found that the longer the WRT, the higher the DOC concentration is in inland waters. In other words, longer WRT and slower water velocity generally result in smaller DC flux in inland waters. More interestingly, the decreasing rate of DC flux in rivers is twice as much as that in lakes and reservoirs; thus, the magnitudes of riverine DOC and DIC fluxes are more sensitive to WRT than lakes and reservoirs. Besides, our analysis suggested that the DOC concentrations in inland waters are positively correlated with the WRT in the temperate zone because biotic production of carbon was greater than its consumption. In contrast, the concentration of DIC and CO 2 in the temperate zone is negatively correlated with the WRT, respectively. In tropical and boreal regions, the DOC concentrations in inland waters are negatively correlated with the WRT because of high temperature- and rainfall-associated hydrologic dynamics in tropical regions and the widely distributed ice cover in the boreal regions. These findings have important implications for studying the global carbon cycle due to the significance of inland water in transporting carbon from land to ocean. Further study on the relationship between WRT and DC export in inland waters of the temperate zone is necessary, particularly for river systems.

St. John's wort (SJW) is a medicinal herb remedy for mild depression. However, long-term use of SJW has raised safety concerns in clinical practice because of drug-drug interactions. Excessive use of acetaminophen (APAP) causes severe hepatotoxicity, but whether SJW modulates APAP-induced liver injury remains unclear. In this study, the effect of long-term SJW administration on APAP-induced acute hepatotoxicity and the involved mechanisms were investigated. Morphological and biochemical assessments clearly demonstrated that SJW exacerbates APAP-induced toxicity. Moreover, SJW markedly promoted glutathione depletion and increased the levels of the APAP-cysteine and APAP-N-acetylcysteinyl adducts in mice, which enhanced APAP metabolic activation and aggravated APAP-induced liver injury. To further elucidate APAP metabolic activation in liver injury induced by SJW, the activities and expression levels of CYP2E1 and CYP3A were measured. The results showed that the activities and expression levels of CYP2E1 and CYP3A were increased after SJW treatment. Furthermore, the PXR-CYP signaling pathway was activated by SJW, and its downstream target genes were upregulated. Collectively, this study demonstrated that the long-term administration of SJW extract led to the metabolic activation of APAP and significantly exacerbated APAP-induced liver injury, which may suggest caution for the clinical use of SJW and APAP.

Although several flow routing (FR) algorithms are developed for hydrological modeling, it is still uncertain how the selection of algorithms may affect model results. This study aims to explore the similarity and dissimilarity in model results among different FR algorithms characterized by single flow direction (SD) and multiple flow direction (MD). The Coupled Hydro-Ecological Simulation System (CHESS) was incorporated with six different FR algorithms (D8, D infinity, MD infinity, MD8, MFD-md, and RMD infinity) and then applied for modeling ecohydrological processes for a semiarid mountainous watershed in the western United States during 1991-2012. Comparisons were made between the model results at the catchment and the grid scale. After slightly adjusting one of the most sensitive soil parameters, all algorithms behave similarly in simulating stream hydrographs. When averaged for the watershed, the modeled ecohydrological variables mostly do not differ significantly (<5%) among the six FR algorithms. Nevertheless, the simulated ecohydrological variables are spatially more autocorrelated under the more dispersive MD algorithms. In addition, there exist significant (>5%) cell-level differences in modeled soil moisture among different FR algorithms, with propagated influences on the simulated evapotranspiration and vegetation growth variables. In hillslopes, the cell-level differences in model results tend to increase significantly as the flows move to the streams. Overall, this study proves that the watershed-level differences in model results among FR algorithms are low after model calibration, while significant differences still occur at the cell level. Thus, observational data are essential for testing which routing algorithm captures better the reality of local ecohydrological processes. Significance StatementThe consideration of flow routing is essential for accurately simulating land surface ecohydrological processes. However, less is known about how the selection of flow routing algorithms may affect the model results. Based on model experiments, we found that the model results under different algorithms do not significantly differ from each other when averaged for the watershed. However, significant differences in model results exist at the individual cell level. These findings are useful for guiding future modeling-related research and also suggest the importance of field studies for testing which routing algorithm can better represent local ecohydrological processes.