Identifying individual's distractor suppression using functional connectivity between anatomical large-scale brain regions.

Distractor suppression (DS) is crucial in goal-oriented behaviors, referring to the ability to suppress irrelevant information. Current evidence points to the prefrontal cortex as an origin region of DS, while subcortical, occipital, and temporal regions are also implicated. The present study aimed to examine the contribution of communications between these brain regions to visual DS. To do it, we recruited two independent cohorts of participants for the study. One cohort participated in a visual search experiment where a salient distractor triggering distractor suppression to measure their DS and the other cohort filled out a Cognitive Failure Questionnaire to assess distractibility in daily life. Both cohorts collected resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate function connectivity (FC) underlying DS. First, we generated predictive models of the DS measured in visual search task using resting-state functional connectivity between large anatomical regions. It turned out that the models could successfully predict individual's DS, indicated by a significant correlation between the actual and predicted DS (r = 0.32, p < 0.01). Importantly, Prefrontal-Temporal, Insula-Limbic and Parietal-Occipital connections contributed to the prediction model. Furthermore, the model could also predict individual's daily distractibility in the other independent cohort (r = -0.34, p < 0.05). Our findings showed the efficiency of the predictive models of distractor suppression encompassing connections between large anatomical regions and highlighted the importance of the communications between attention-related and visual information processing regions in distractor suppression. Current findings may potentially provide neurobiological markers of visual distractor suppression.

The Pathophysiology, Prognosis and Treatment of Hypertension in Females from Pregnancy to Post-menopause: A Review.

PURPOSE OF REVIEW: We summarise the physiological changes and risk factors for hypertension in females, potential sex-specific management approaches, and long-term prognosis. KEY FINDINGS: Pregnancy and menopause are two key phases of the life cycle where females undergo significant biological and physical changes, making them more prone to developing hypertension. Gestational hypertension occurs from changes in maternal cardiac output, kidney function, metabolism, or placental vasculature, with one in ten experiencing pregnancy complications such as intrauterine growth restriction and delivery complications such as premature birth. Post-menopausal hypertension occurs as the protective effects of oestrogen are reduced and the sympathetic nervous system becomes over-activated with ageing. Increasing evidence suggests that post-menopausal females with high blood pressure (BP) experience greater risk of cardiovascular events at lower BP thresholds, and greater vulnerability to treatment-related adverse effects. Hypertension is a key risk factor for cardiovascular disease in females. Current BP treatment guidelines and recommendations are similar for both sexes, without addressing sex-specific factors. Future investigations into ideal diagnostic thresholds, BP control targets and treatment regimens in females are needed.

Propofol inhibits myocardial injury induced by microvesicles derived from hypoxia-reoxygenated endothelial cells via lncCCT4-2/CCT4 signaling.

BACKGROUND: Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. METHODS: Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. RESULTS: In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. CONCLUSIONS: Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis.

High-throughput screening and quantitative analysis of hidden ingredients in plant protection products by GC-MS/MS.

Hidden ingredients in plant protection products (PPPs) threaten public health, food trade, and the environment. In this study, we developed a high-throughput screening method of 639 hidden ingredients in PPPs using GC-MS/MS in multiple reaction monitoring mode. Results showed that the qualitative criteria of retention time (tR) shift and uncertainty of qualifier to quantifier ratio in the commercially available Shimadzu Smart Pesticides Database were set at < 0.17 min and < 30%, respectively, which could be used to tentatively identify compounds without standards. The limits of quantification were 0.01-0.05 mg/kg. A wide linear range of 10-1000 µg/L was observed with R2 ≥ 0.975. Recoveries from three types of PPP formulations were 62.08%- 126.3%, with relative standard deviations < 15.7%. Finally, this method was applied to screen and quantify hidden ingredients in 91 plant protection products (PPPs) samples collected from online sales in China. Only one hidden ingredient, dimethomorph (1.6 g/kg), was detected in the polyoxin formulation (15% wettable powder). The results will be helpful in assessing the potential risks of hidden ingredients in PPPs.

Bidirectional relationship between bullying victimization and functions of aggression in adolescents: The mediating effect of teacher justice.

INTRODUCTION: Bullying victimization and aggression are frequent phenomena among adolescents and have been linked to various mental health problems. Although the correlation between bullying victimization and aggression is well-documented, the direction between the two has been debated. Moreover, the underlying mechanism through which victimization influences aggression or vice versa has gained little attention. The current study used data across two-time points to address this gap and explore the reciprocal relationships between victimization and aggression. The mediating role of teacher justice and related gender differences were also examined. METHODS: A total of 2462 Chinese adolescents (50.9% boys; Mage = 13.95 years, SD = 0.60) completed measures on two occasions in 1 year with 6-month assessment intervals. Structural equation modeling was used to examine the longitudinal relations among the variables. RESULTS: Results found that bullying victimization significantly and positively predicted both reactive and proactive aggression over time among the total sample. Reactive aggression significantly positively predicted victimization, while proactive aggression negatively predicted victimization in boys. Furthermore, teacher justice mediated the relationships between victimization and both functions of aggression. Mediation was gender-specific, with a significant mediating effect on girls. CONCLUSIONS: The results reveal the violent cycle of bullying victimization and aggression and underscore the role of teacher justice in this process. These findings have important implications for targeted interventions.

Joint Developmental Trajectories of Likability and Popularity: Associations with Social Behavior among Chinese Adolescents.

The beginning of secondary school is a critical time point of adolescents' development as they entered a new peer context in which social status was re-established. As the key indicators of social status, likability and popularity co-occur but also display distinct developmental trajectories over time. Nevertheless, little is known about the joint developmental trajectories of likability and popularity among adolescents and how identified trajectories are associated with important social behavior. The current study examined the joint developmental trajectories of likability and popularity among Chinese adolescents and their associations with social behavior (prosocial behavior, aggression, and peer victimization) over time. A total of 1509 Chinese 7th grade students (53.6% male, Mage = 13.1, SD = 0.67) participated in self-report and peer nomination assessments on three occasions at 6-month intervals. Parallel process latent growth mixture models revealed four distinct trajectories of likability and popularity: social status decreasing, average, high social status, and social status increasing. The high social status group showed the highest levels of prosocial behavior, the lowest levels of peer victimization, and higher aggression than the average group. The social status decreasing group and social status increasing group exhibited the lower prosocial behavior as well as the higher aggression and peer victimization compared to the average group over time. The findings highlight the co-occurrence but diversity of developmental patterns of likability and popularity in adolescence.

Profiles and Transitions of Loneliness and Depressive Symptoms among Migrant Children: Predictive Role of Bullying Victimization.

Although loneliness and depressive symptoms are particularly prominent among migrant children and often occur simultaneously, little is known about the co-occurring and transitional nature of loneliness and depressive symptoms among migrant children, and the role of bullying victimization on their profiles and transitions. This study examined the profiles and transitions of loneliness and depressive symptoms among migrant children using latent profile analysis and latent transition analysis, as well as how bullying victimization predicted their profile memberships and transitions. A total of 692 migrant children (55.3% males, Mage = 9.41, SD = 0.55, range = 8 to 12 years old at T1) participated in both two waves of the study over six months. The results indicated that low profile (59.2%), moderate profile (22.0%), moderately high profile (14.3%), and high profile (4.5%) were identified at Time 1; low profile (69.4%), predominantly loneliness profile (16.8%), predominantly depressive symptoms profile (6.5%), and high profile (7.3%) were identified at Time 2. Migrant children in at-risk profiles displayed varying degrees of transition. Migrant children experiencing more bullying victimization were more likely to belong or transition to at-risk profiles. The findings highlight the importance of subgroup differences considerations in understanding the co-occurring and transitional nature of loneliness and depressive symptoms, as well as the predictive role of bullying victimization, informing effective strategies for prevention and intervention.

The impacts of cropland balance policy on habitat quality in China: A multiscale administrative perspective.

Cropland protection policies are implemented to guarantee food security, especially the cropland balance policy in China. Although these policies alleviate the quantitative loss of cropland, they cause a serious decline in habitat quality and reduce biodiversity. With the reform trial of China's cropland balance policy from the within-province scale to the cross-provincial scale, the evaluation of habitat quality for obtaining cropland balance at different administrative scales is necessary to help seek sustainable strategies of cropland protection. Thus, taking Chinese mainland as the study area, this research assessed the different impacts of the cropland balance policy on habitat quality during 2000-2015 and 2015-2030 at national, provincial, municipal and county scales on the basis of the LAND System Cellular Automata model for Potential Effects (LANDSCAPE) and the Integrated Valuation of Ecosystem Services and Tradeoffs model (InVEST). The results revealed that (1) the loss of habitat quality by compensated cropland was 4.02 times that of the loss by occupied cropland in 2000-2015. Compared with occupied cropland, compensated cropland dominated the impacts of cropland change on habitat quality. (2) For both cropland quantity balance and cropland quality balance, habitat quality was slightly lost the most on the national scale in 2030. In detail, the greatest loss of habitat quality mostly occurred in areas where the ecological environment is already vulnerable at the national scale, whereas habitat quality was relatively less in these areas at the provincial, municipal and county scales. (3) Under the same administrative scales, habitat quality was lost more in cropland quality balance scenarios than in cropland quantity balance scenarios. The loss of habitat quality caused by cropland quality balance at national, provincial, municipal and county scales was 1.25, 1.05, 0.90 and 1.37 times higher than that by cropland quantity balance, respectively. The research highlights that considering the differentiated loss of habitat quality caused by cropland protection is quite important when implementing the cropland balance policy and land use planning.

Dietary mulberry-leaf flavonoids supplementation improves liver lipid metabolism and ovarian function of aged breeder hens.

Mulberry-leaf flavonoids (MF), extracted from mulberry leaves, exert antioxidant and hypolipidemic effects. The purpose of this experimental study was to investigate the effects of dietary MF on the ovarian function and liver lipid metabolism of aged breeder hens. We used 270 (60-weeks-old) Qiling breeder hens randomly assigned in 3 treatments with supplemental dietary MF doses (0, 30, 60 mg/kg). The results showed that dietary MF significantly improved the egg-laying rate, followed by the reduced feed conversion rate (FCR) (p < 0.05). However, there is no obvious difference in hatchability and fertilised eggs hatchability among the three groups (p > 0.05). The level of T-CHO, LDL-C and AKP in serum was reduced, and the HDL-C concentrations were increased by dietary MF (p < 0.05). MF treatment also improved the antioxidant capacity and reduced the apoptotic index of the ovary (p < 0.05). Additionally, dietary MF significantly increased the serum estradiol (E2) levels (p < 0.05) and the transcription level of CYP19A1 and LHR in the ovary (p < 0.05). Dietary MF enhanced fatty acid ß-oxidation in the liver via up-regulating the mRNA expressions of PPARα and CPT-I (p < 0.05). Moreover, the HMF group significantly decreased mRNA expressions of SREBP-1c (p < 0.05) and increased mRNA expressions of ERα, VTG-Ⅱ and ApoB in the liver (p < 0.05). In conclusion, dietary MF could improve the reproduction performance of aged breeder hens through improving ovary function and hepatic lipid metabolism.

Determination of PAR4 numbers on the surface of human platelets: no effect of the single nucleotide polymorphism rs773902.

The thrombin receptor, protease-activated receptor 4 (PAR4), is important for platelet activation and is the target of emerging anti-thrombotic drugs. A frequently occurring single nucleotide polymorphism (SNP; rs773902) causes a function-altering PAR4 sequence variant (NC_000019.10:p.Ala120Thr), whereby platelets from Thr120-expressing individuals are hyper-responsive to PAR4 agonists and hypo-responsive to some PAR4 antagonists than platelets from Ala120-expressing individuals. This altered pharmacology may impact PAR4 inhibitor development, yet the underlying mechanism(s) remain unknown. We tested whether PAR4 surface expression contributes to the altered receptor function. Quantitative flow cytometry was used to determine the absolute number of PAR4 on platelets from individuals subsequently genotyped at rs773902. We detected 539 ± 311 PAR4 per platelet (mean ± SD, n = 84). This number was not different across rs773902 genotypes. This first determination of cellular PAR4 numbers indicates variations in platelet surface expression do not explain the altered pharmacology of the rs773902 PAR4 sequence variant.

Using PAR4 Inhibition as an Anti-Thrombotic Approach: Why, How, and When?

Protease-activated receptors (PARs) are a family of four GPCRs with a variety of cellular functions, yet the only advanced clinical endeavours to target these receptors for therapeutic gain to date relates to the impairment of platelet function for anti-thrombotic therapy. The only approved PAR antagonist is the PAR1 inhibitor, vorapaxar-the sole anti-platelet drug against a new target approved in the past 20 years. However, there are two PARs on human platelets, PAR1 and PAR4, and more recent efforts have focused on the development of the first PAR4 antagonists, with first-in-class agents recently beginning clinical trial. Here, we review the rationale for this approach, outline the various modes of PAR4 inhibition, and speculate on the specific therapeutic potential of targeting PAR4 for the prevention of thrombotic conditions.

Simplification of Carbon Bond Mechanism IV (CBM-IV) under Different Initial Conditions by Using Concentration Sensitivity Analysis.

Carbon Bond Mechanism IV (CBM-IV) is a widely used reaction mechanism in which VOCs are grouped according to the molecular structure. In the present study, we applied a sensitivity analysis on the CBM-IV mechanism to clarify the importance of each reaction under two different initial conditions (urban and low-NO scenarios). The reactions that exert minor influence on the reaction system are then screened out from the mechanism, so that a reduced version of the CBM-IV mechanism under specific initial conditions can be obtained. We found that in a typical urban condition, 11 reactions can be removed from the original CBM-IV mechanism, and the deviation is less than 5% between the results using the original CBM-IV mechanism and the reduced mechanism. Moreover, in a low-NO initial condition, two more reactions, both of which are nitrogen-associated reactions, can be screened out from the reaction mechanism, while the accuracy of the simulation is still maintained. It is estimated that the reduction of the CBM-IV mechanism can save 11-14% of the computing time in the calculation of the chemistry in a box model simulation.

Effects of evolving quality of landfill leachate on microbial fuel cell performance.

Microbial fuel cell (MFC) is a novel technology for landfill leachate treatment with simultaneous electric power generation. In recent years, more and more modern landfills are operating as bioreactors to shorten the time required for landfill stabilization and improve the leachate quality. For landfills to operate as biofilters, leachate is recirculated back to the landfill, during which time the organics of the leachate can be decomposed. Continuous recirculation typically results in evolving leachate quality, which chronologically corresponds to evolution stages such as hydrolysis, acidogenesis, acetogenesis, methanogenesis, and maturation. In this research, variable power generation (160 to 230 mW m-2) by MFC was observed when leachate of various evolutionary stages was used as the feed. The power density followed a Monod-type kinetic model with the chemical oxygen demand (COD) equivalent of the volatile fatty acids (VFAs) ( p < 0.001). The coulombic efficiency decreased from 20% to 14% as the leachate evolved towards maturation. The maximum power density linearly decreased with the increase of internal resistance, resulting from the change of the conductivity of the solution. The decreased conductivity boosted the internal resistance and consequently limited the power generation. COD removal as high as 90% could be achieved with leachate extracted from appropriate evolutionary stages, with a maximum energy yield of 0.9 kWh m-3 of leachate. This study demonstrated the importance of the evolving leachate quality in different evolutionary stages for the performance of leachate-fed MFCs. The leachate extracted from acidogenesis and acetogenesis were optimal for both COD reduction and energy production in MFCs.

Imidacloprid triggered changes in strawberry fruits on edible quality and phenolic profiles by applied at two growth stages.

Increasing evidence showed that imidacloprid affects plants' abiotic or biotic stress tolerance. However, the effects of imidacloprid on the quality of fruits remain elusive. This work aimed to study the effects of imidacloprid applied at different growth stages on the edible quality and phenolic profile of strawberry fruit in the field experiment. For the first time, lower fruit quality was observed in the mature strawberry fruits after imidacloprid treatment at the fruit-bearing completion stage (five days after pollination). Compared to the control group, the mature strawberry fruit wights and the SCC/TA ratio declined about 18.2-30.0 % and 10.3-16.8 %, respectively. However, those attributes did not occur in the mature strawberry fruits by imidacloprid treatment at the fruit maturation stage (30 days after pollination). Among the 30 phenolic compounds, nine presented significant up-regulation or down-regulation after imidacloprid application at two different growth stages, suggesting that the application period played an essential role in evaluating the effects of imidacloprid on the quality of fruits. A significant effect on fruit quality was presented at the strawberry early growth stage treated by imidacloprid. This study provided a new insight into how and when imidacloprid affects the quality of strawberry fruits, contributing to the future's more scientific application of imidacloprid on strawberries.

Occurrence and distribution of trisiloxane ethoxylates in citrus orchard soils in China: Analytical challenges.

Trisiloxane ethoxylates (TSEOn) are widely used as agricultural surfactants due to their significant synergism with the active ingredients of pesticides, generally, including three typical end groups which are hydroxyl (TSEOn-H), methoxy (TSEOn-CH3), and acetoxy (TSEOn-COCH3), respectively. However, the potential ecotoxicological and endocrine-disrupting risks of TSEOn congeners have recently attracted ever-growing concern. Above all, there is limited research on the concentration levels of TSEOn in agroecosystems. This study, simultaneous analysis of 39 TSEOn oligomers in citrus orchard soils in China was implemented by the modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method detection limits (MDLs) and the method quantification limits (MQLs) for TSEOn were 0.003-0.07 µg/kg and 0.01-0.20 µg/kg, respectively. The recoveries for TSEOn oligomers in soils ranged from 81 % âˆ¼ 106 % with related standard deviations (RSDs) < 7 %. This newly developed UPLC-MS/MS method with high sensitivity and stability allows us to successfully trace the occurrence of TSEOn congeners in the citrus orchard soils from 3 provinces and 1 municipality in China. The detected concentrations of TSEOn-H oligomers in the sampled soils ranged from 0.02 to 0.288 µg/kg (dry weight). The congener profiles of TSEOn-H were dominated by TSEOn-H (n = 6- 8) in the soils. Additionally, the total concentrations of TSEOn-H congeners (ΣTSEOn-H) in the soils were in the range of 0.03 to 1.49 µg/kg. A comparison of ΣTSEOn-H distribution among the different citrus orchard soils indicated a higher level of ΣTSEOn-H in the soil samples collected from Zhejiang Province. Notably, TSEOn-CH3 or TSEOn-COCH3 oligomers were not detected in the tested soils. To the best of our knowledge, this is the first report on the occurrence and distribution of TSEOn congeners in agricultural soils.

Dissipation and potential risk of tristyrylphenol ethoxylate homologs in peanuts by spraying and root irrigation: A comparative assessment.

Peanuts, known for their nutritional value, health benefits, and delicious taste, are susceptible to agricultural chemical contamination, posing a challenge to the peanut industry in China. While tristyrylphenol ethoxylates (TSPEOs) have garnered attention for their widespread use in pesticide formulations, their dissipation and potential risks in peanuts remain a gap in knowledge. This study, unique in its focus on TSPEOs, investigates their dissipation and potential risks under two common application modes: spraying and root irrigation. The concentration of total TSPEOs in peanut plants was significantly higher when sprayed (435-37,693 µg/kg) than in root irrigation (24-1602 µg/kg). The dissipation of TSPEOs was faster in peanuts and soil when sprayed, with half-lives of 3.67-5.59 d (mean: 4.37 d) and 5.41-7.07 d (mean: 5.95 d), respectively. The residue of TSPEOs in peanut shells and soil were higher with root irrigation (8.9-65.2 and 25.4-305.1 µg/kg, respectively) than with spraying (5.4-30.6 and 8.8-146.5 µg/kg, respectively). These results indicated that the dissipation behavior of TSPEOs in peanuts was influenced by application modes. While the healthy and ecological risk assessments of TSPEOs in soil and peanut shells showed no risks, root irrigation might pose a higher potential risk than spraying. This research provides valuable data for the judicious application of pesticides during peanut cultivation to enhance pesticide utilization and reduce potential risks.

Effects of maternal hawthorn-leaf flavonoid supplementation on the intestinal development of offspring chicks.

Metabolic disorders in maternal generation during the late egg-laying period have adverse effects on neonatal development. The study was conducted to clarify the effects of maternal feeding of hawthorn-leaf flavonoid (HF) on the microbial community and intestinal development of chicks. Breeder hens were fed a basic corn-soybean diet, while the treatment groups were supplemented with 30 or 60 mg/kg HF. The offspring chicks were divided into CON, LHF, and HHF groups according to the maternal treatments. Maternal HF supplementation at 60 mg/kg increased the average daily gain and decreased the feed conversion rate of chicks (P < 0.05), but did not affect the average daily feed intake. HF treatments increased the villus height to crypt depth ratio and up-regulated the protein expressions of PCNA, IGF-1R, PI3K and p-mTOR in the jejunum (P < 0.05) of 1-day-old and 14-day-old chicks. Additionally, maternal HF treatment up-regulated the mRNA expression of tight junction transmembrane proteins (occludin) and scaffolding proteins (ZO-1 and ZO-2) in the jejunum of 1-day-old chicks (P < 0.05). Moreover, the maternal effects of HF on ZO-1 expression could last for 14 d (P < 0.05). Interestingly, dietary HF supplementation altered the vertically transmitted microbial community from breeder hens to chicks, especially increased the relative abundance of probiotics (i.e., Clostridium_sensu_stricto_1) in the meconium of chicks (P < 0.05), which may help with early gut microbiota colonization and intestinal development. In summary, dietary HF supplementation for breeder hens altered the bacterial community of neonates and might promote intestinal development of chicks through the IGF-1R/AKT/mTOR signaling pathway.

Development of a therapeutic monoclonal antibody against circulating adipocyte fatty acid binding protein to treat ischaemic stroke.

BACKGROUND AND PURPOSE: Adipocyte fatty acid-binding protein (A-FABP) exacerbates cerebral ischaemia injury by disrupting the blood-brain barrier (BBB) through inducing expression of MMP-9. Circulating A-FABP levels positively correlate with infarct size in stroke patients. We hypothesized that targeting circulating A-FABP by a neutralizing antibody would alleviate ischaemic stroke outcome. EXPERIMENTAL APPROACH: Monoclonal antibodies (mAbs) against A-FABP were generated using mouse hybridoma techniques. Binding affinities of a generated mAb named 6H2 towards various FABPs were determined using Biacore. Molecular docking studies were performed to characterize the 6H2-A-FABP complex structure and epitope. The therapeutic potential and safety of 6H2 were evaluated in mice with transient middle cerebral artery occlusion (MCAO) and healthy mice, respectively. KEY RESULTS: Replenishment of recombinant A-FABP exaggerated the stroke outcome in A-FABP-deficient mice. 6H2 exhibited nanomolar to picomolar affinities to human and mouse A-FABP, respectively, with minimal cross-reactivities with heart and epidermal FABPs. 6H2 effectively neutralized JNK/c-Jun activation elicited by A-FABP and reduced MMP-9 production in macrophages. Molecular docking suggested that 6H2 interacts with the "lid" of the fatty acid binding pocket of A-FABP, thus likely hindering the binding of its substrates. In mice with transient MCAO, 6H2 significantly attenuated BBB disruption, cerebral oedema, infarction, neurological deficits, and decreased mortality associated with reduced cytokine and MMP-9 production. Chronic 6H2 treatment showed no obvious adverse effects in healthy mice. CONCLUSION AND IMPLICATIONS: These results establish circulating A-FABP as a viable therapeutic target for ischaemic stroke, and provide a highly promising antibody drug candidate with high affinity and specificity.

Maternal supplementation with mulberry-leaf flavonoids improves the development of skeletal muscle in the offspring of chickens.

The development of skeletal muscle is a crucial factor in determining the meat yield and economic benefits of broiler production. Recent research has shown that mulberry leaves and their extracts can be used to significantly improve the growth performance of livestock and poultry. The present study aims to elucidate the mechanisms involved in the regulation of skeletal muscle development in broiler offspring by dietary mulberry-leaf flavonoids (MLF) supplementation from the perspective of maternal effect theory. A total of 270 Qiling broiler breeder hens were randomly assigned to 3 treatments with different doses of MLF (0, 30, 60 mg/kg) for 8 weeks before collecting their fertilized eggs. The chicken offspring at 13 and 19 d of embryonic stage, and from 1 to 28 d old after hatching were included in this study. The results showed that maternal supplementation increased the breast muscle weight and body weight of the offspring at the embryo and chick stages (P < 0.05). This was followed by increased cross-sectional area of pectoral muscle fibres at 14 d (P < 0.05). Further determination revealed a tendency towards increased serum levels of insulin-like growth factor 1 (IGF-1) (P = 0.092) and muscle fibre count (P = 0.167) at 1 d post-hatching following maternal MLF treatment, while serum uric acid (UA) was decreased at 14 d after hatching (P < 0.05). Moreover, maternal MLF supplementation significantly up-regulated the mRNA expression of the myogenic regulatory factor Myf5 in skeletal muscle at the both embryonic and growth stages (P < 0.05). The relative abundance of the downstream protein of BMPR2, Smad1 and p-Smad1/5/9 in the TGFß signalling pathway was significantly increased by maternal MLF treatment. Meanwhile, the increased expression of the target protein p-mTOR in the breast muscle of the offspring chicks is in accordance with the improved growth rate of the breast and the body. In conclusion, maternal MLF supplementation can promote muscle protein metabolism and muscle fibre development of chick embryos through upregulation of Myf5 expression and BMP/p-Smad1/5/9 axis, thereby improving growth performance of slow growing broiler.

Combustion Growth of NiFe Layered Double Hydroxide for Efficient and Durable Oxygen Evolution Reaction.

NiFe layered double hydroxide (LDH) with abundant heterostructures represents a state-of-the-art electrocatalyst for the alkaline oxygen evolution reaction (OER). Herein, NiFe LDH/Fe2O3 nanosheet arrays have been fabricated by facile combustion of corrosion-engineered NiFe foam (NFF). The in situ grown, self-supported electrocatalyst exhibited a low overpotential of 248 mV for the OER at 50 mA cm-2, a small Tafel slope of 31 mV dec-1, and excellent durability over 100 h under the industrial benchmarking 500 mA cm-2 current density. A balanced Ni and Fe composition under optimal corrosion and combustion contributed to the desirable electrochemical properties. Comprehensive ex-situ analyses and operando characterizations including Fourier-transformed alternating current voltammetry (FTACV) and in situ Raman demonstrate the beneficial role of modulated interfacial electron transfer, dynamic atomic structural transformation to NiOOH, and the high-valence active metal sites. This study provides a low-cost and easy-to-expand way to synthesize efficient and durable electrocatalysts.