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Myocardial ischemia-reperfusion injury (MIRI) poses a significant threat to patients with coronary heart disease. Adenosine A2A receptors have been known as a protective role in MIRI by regulating autophagy, so we assumed that activation of adenosine A2B receptor (A2BAR) might exert a similar effect during MIRI and underlying mechanism be related to proteostasis maintenance as well. In situ hearts were subjected to 30 min of ischemia and 120 min of reperfusion (IR), while in vitro cardiomyocytes from neonatal rats experienced 6 h of oxygen-glucose deprivation followed by 12 h of reoxygenation (OGDR). Initially, we observed that post-ischemia-reperfusion induced autophagy flux blockade and ERS both in vivo and in vitro , evident through the increased expression of p62, LC3II, and BIP, which indicated the deteriorated proteostasis. We used a selective A2BAR agonist, Bay 60–6583, to explore the positive effects of A2BAR on cardiomyocytes and found that A2BAR activation rescued damaged cardiac function and morphological changes in the IR group and improved frail cell viability in the OGDR group. The A2BAR agonist also alleviated the blockage of autophagic flux, coupled with augmented ERS in the IR/OGDR group, which was reassured by using an autophagy inhibitor chloroquine (CQ) and ERS inhibitor (4-PBA) in vitro. Additionally, considering cAMP/PKA as a well-known downstream effector of A2BAR, we utilized H89, a selective PKA inhibitor. We observed that the positive efficacy of Bay 60–6583 was inhibited by H89. Collectively, our findings demonstrate that the A2BAR/cAMP/PKA signaling pathway exerts a protective role in MIRI by mitigating impaired autophagic flux and excessive ERS. [Display omitted] • Myocardial I/R injury is related to autophagy and ERS pathogenesis. • A2B receptor activation reduces reperfusion-induced cardiomyocyte injury. • Bay 60–6583 regulates ERS and autophagy flux via the cAMP/PKA signaling pathway. [ABSTRACT FROM AUTHOR]

The 2-amino-3-methyl-imidazole [4,5-f] quinoline (IQ) is a compound generated during the Maillard reaction while heating protein-rich foods and has been classified as a class 2A possible human carcinogen that has attracted ongoing public concern. However, the formation mechanism of IQ remains unknown. Herein, we investigated the formation mechanism of IQ in the Maillard reaction model system under various reaction conditions (temperature, time, and pH). The results showed that various conditions significantly influenced the precursors, reactive carbonyl species, and IQ formation (P < 0.05). There was regularity between IQ and various conditions, and the R 2 in the fitting curves were between 0.90 and 0.99. To further explore the relationship between IQ and various conditions, a partial least squares (PLS) prediction model was constructed. The model indicates that temperature is a significant contributor to the formation of IQ during the Maillard reaction. Further analysis indicated that crotonaldehyde plays a vital role. Crotonaldehyde could promote IQ formation at low addition levels but inhibit its formation at high addition levels. Possible effects of crotonaldehyde on the formation of IQ were proposed. Overall, this research will help to identify more effective ways to reduce the formation of IQ in meat products, which can improve their safety for human consumption. [Display omitted] • The formation of IQ in the Maillard reaction model system was studied. • The regularity between the formation of IQ and various conditions was proposed. • The partial least squares (PLS) model was constructed for the prediction of IQ formation. • The effects of crotonaldehyde during the formation of IQ were illustrated. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel ferulic acid derivatives with oxadiazole were designed and synthesized. • The synthesized compounds showed significantly antiviral activity. • Compound 6 h can intensify the activities of some defensive enzymes. • 6 h regulates phenylpropanoid biosynthesis pathway and chloroplast function. • Some of the synthesized compounds could be used as potential elicitors. A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans -ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6 h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a , 6b , 6e , 6f and 6 h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6 h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV. [ABSTRACT FROM AUTHOR]

The FLT4 gene plays an important role in the onset and progression of obesity and is involved in the structure and function of lymphatic vessels. By inducing a mouse obesity model with a high-fat diet and knocking out the FLT4 gene, which is associated with lymphatic vessel growth in mice, FLT4+/− mice were found to be susceptible to high-fat diet-induced obesity, with significant accumulation of visceral fat. BODIPY™ FL C 16 imaging revealed dilated and branched mesenteric lymphatic vessels in FLT4+/− mice. Immunofluorescence staining showed that FLT4+/− exacerbated the morphological abnormalities of lymphatic vessels and submucosal lymphatic vessels in visceral adipose tissue of obese mice, accompanied by macrophage infiltration around lymphatic vessels. In addition, FLT4 knock down increased the proportion of M1-type macrophages in the adipose tissue of the epididymis, indicating significant chronic inflammation in FLT4+/− obese mice. These findings provide new evidence for the involvement of lymphatic vessel morphological abnormalities in the onset and progression of obesity and highlight the importance of further investigation of FLT4 to better understand the mechanism of HFD-induced obesity and to develop related treatments. • Wild-type hyper-fat mice were obese and developed mesenteric lymphangiectasia. • On a high-fat diet, FLT4+/− mice gained more weight and developed abnormal glucose tolerance than wild-type mice. • In obese FLT4+/− mice, fat accumulated in the mesentery, and lymphatic vessels increased in diameter and branching. • Obese FLT4+/- mice showed macrophage accumulation around mesenteric and epididymal adipose tissue lymphatic vessels. [ABSTRACT FROM AUTHOR]

• Screening candidate circpdlim5a from the Japanese flounder transcriptome. • Circpdlim5a has a stable structure and high RNase R tolerance. • Distributed in nucleus and cytoplasm and highly expressed in nucleus. • Circpdlim5a inhibits the expression of proliferation and differentiation genes. Circular RNAs (circRNAs) are non-coding RNAs with endogenous regulatory functions, including regulating skeletal muscle development. However, its role in the development of skeletal muscle in Japanese flounder (Paralichthys olivaceus) is not clear. Therefore we screened a candidate circpdlim5a, which is derived from the gene pdlim5a , from the skeletal muscle transcriptome of Japanese flounder. We characterized circpdlim5a, which was more stable compared to the linear RNA pdlim5a. Distributional characterization of circpdlim5a showed that circpdlim5a was predominantly distributed in the nucleus and was highly expressed in the skeletal muscle of adult Japanese flounder (24 months). When we further studied the circpdlim5a function, we found that it inhibited the expression of proliferation and differentiation genes according to the over-expression experiment of circpdlim5a in myoblasts. We concluded that circpdlim5a may inhibit the proliferation and differentiation of myoblasts and thereby inhibit skeletal muscle development in Japanese flounder. This experiment provides information for the study of circRNAs by identifying circpdlim5a and exploring its function, and offers clues for molecular breeding from an epigenetic perspective. [ABSTRACT FROM AUTHOR]

Apoptosis genes Egr2 , Fas and FasL are related to immune responses. However, the mechanism of these genes inducing apoptosis in fish are still not very clear. An acute hypoxia treatment (1.73 ± 0.06 mg/L) for 24 h was carried out on Japanese flounder (Paralichthys olivaceus). The increasingly dense apoptotic signals at 3 h, 6 h, 12 h by TUNEL in skeletal muscle indicated that hypoxia could quickly affect muscle growth and development. Furthermore, we concluded that the Egr2-FasL-Fas signal pathway, which was located at the upstream of apoptotic executor protein caspases, was related to the apoptosis by quantitative real-time PCR, protein concentration detection in ELISA and double gene in situ hybridization methods. The mechanism of the pathway was researched in transcription regulation and epigenetic modification by dual-luciferase reporter assay and bisulfite modified method, respectively. Egr2, as a transcription factor, could up-regulate the expression of FasL gene. And its binding site was mainly between −479 to −1 of FasL gene promoter. The 5th CpG dinucleotides (−514) methylation levels in FasL gene were significantly affected by hypoxia, and they were negatively correlated with its expressions. These suggested that the −514 site may be a very important site to regulate the FasL gene expression. Above results, we concluded that hypoxia activated the immune related signal pathway Egr2-FasL-Fas to induced skeletal muscle apoptosis to affect growth and development of Japanese flounder. The study revealed the mechanism of hypoxia induced apoptosis, which could provide a reference for fish immunity and aquaculture management. • Skeletal muscle cell immune response was activated by acute hypoxia stress. • The immunity was related to Egr2-FasL-Fas signal pathway to induce apoptosis. • Egr2 transcriptionally regulated the expression of FasL gene. • Hypoxia acts on the signal pathway by epigenetic modification. [ABSTRACT FROM AUTHOR]

Water diversion has been widely utilized to enhance lake water quality and mitigate cyanobacterial blooms. However, previous studies have mainly focused on investigating the effects of water diversion on water quality or aquatic ecological health. Consequently, there is limited research investigating the combined impact of water diversion on the water quality and the ecological health of eutrophic lakes, and whether the WQI and phytoplankton assemblages demonstrate similar patterns following water diversion. In this study, the effects of water diversion on the ecosystem health of eutrophic lakes were comprehensively evaluated based on the WQI indices and phytoplankton assemblages during the NWDP-21 and WDP-22. The results showed that the annual mean of WQI increased from 52.02 to 54.36 after water diversion, which improved the water quality of the lake, especially NH 3 –N and TN decreased by 58.6% and 15.2%, respectively. The phytoplankton assemblages changed significantly before and after water diversion, and we observed that the total biomass of phytoplankton decreased by 12.3% and phytoplankton diversity indices (Shannon-Wiener diversity, Pielou evenness, and Simpson index) increased by 8.6%–8.9% after water diversion, with an improvement in the connectivity and stability of the phytoplankton. Notably, enhanced adaptations of rare sub-communities for resource use in water diversion environments, and water diversion inhibited the dispersal ability of dominant functional groups, and the effects of hydrological disturbances on the structure of phytoplankton assemblage favored the ecological health of eutrophic lakes. VPA analysis further reveals that water diversion alters the drivers of phytoplankton functional group biomass and phytoplankton diversity. The results of the PLS-PM analysis clarify that water diversion indirectly impacts the total phytoplankton biomass and phytoplankton diversity primarily by modifying light availability. Significant correlations are observed between the dominant functional groups biomass and diversity indices of WQI. The trends in changes observed in water quality indices and phytoplankton following water diversion align with the evaluation of water ecological health. This study provides valuable guidance for the ecological management of the diversion project in Yilong Lake and serves as a reference for similar projects in other lakes. [Display omitted] • Variations in WQI and phytoplankton assemblages integrated to evaluate the positive ecological effects of water diversions. • Rare sub-communities more stable after water diversion. • Hydrodynamic disturbances from water diversions inhibit the dispersal ability of many phytoplankton groups. • WQI was significantly correlated with major phytoplankton functional groups and phytoplankton diversity. • The increased availability of light after water diversion indirectly affects total phytoplankton biomass and diversity. [ABSTRACT FROM AUTHOR]

Vibrio anguillarum infection can activate NF-κB/TNFα pathway in the immune organs of fish. Fish muscle is also an important immune organ, but the research on its immune function is few. Our aim was to study regulating mechanism of NF-κB and TNFα gene expressions in the muscle of Japanese flounder (Paralichthys olivaceus) which was under Vibrio anguillarum infection (0, 24, 48, 72 and 96 h). The results showed that the expressions of NF-κB and TNFα increased significantly at 48 h, and there was a significant positive correlation between them. In situ hybridization confirmed the co-existence of NF-κB and TNFα genes in Japanese flounder muscle. Interestingly, the expression of the TNFα gene was regulated by the DNA methylation and its methylation level was negatively correlated with the expression. The lowest methylation level of TNFα occurred at 48 h under Vibrio anguillarum infection (P < 0.05). And more, when the fragment (−2122 ∼ −730) was deleted on TNFα gene promoter, double luciferase activity was the highest, indicating that fragment (−730–0) was the transcription factor binding region. The site (−78 ~ −69) on the fragment (−730–0) binding NF-κB was mutated, and double luciferase activity decreased significantly. The results confirmed that the site (−78 ~ −69) was indeed an important binding site for NF-κB. In addition, the activity of TNFα in the serum of Japanese flounder changed with the prolongation of vibrio anguillarum infection, and the concentration of other immune factors such as ALP, ALT, AST and LDH also changed in the muscle under vibrio anguillarum infection. They all showed a trend of first increasing and then decreasing. Above studies implied that Japanese flounder responded to Vibrio anguillarum infection at the immune level with the change of its methylation status and the activation of transcription factor. By studying the mechanism of immune pathways, understanding the response to immune stress is great significant to the research of fish breeding for disease resistance. • Immune stress of NF-κB/TNFα pathway immune gene caused by Vibrio anguillarum infection. • The change of epigenetic DNA methylation modification caused by Vibrio anguillarum infection. • The binding site of transcription factor NF-κB on TNFα promoter region was identified. • DNA methylation regulation and transcription factor worked together on immune regulation. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide. The burden of cancer incidence and mortality is increasing rapidly. New approaches to cancer prevention and treatment are urgently needed. Natural products are reliable and powerful sources for anticancer drug discovery. Baicalin and baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, a multi-purpose traditional medicinal plant in China, exhibit anticancer activities against multiple cancers. Of note, these phytochemicals exhibit extremely low toxicity to normal cells. Besides their cytotoxic and cytostatic activities toward diverse tumor cells, recent studies demonstrated that baicalin and baicalein modulate a variety of tumor stromal cells and extracellular matrix (ECM) in the tumor microenvironment (TME), which is essential for tumorigenesis, cancer progression and metastasis. In this review, we summarize the therapeutic potential and the mechanism of action of baicalin and baicalein in the regulation of tumor microenvironmental immune cells, endothelial cells, fibroblasts, and ECM that reshape the TME and cancer signaling, leading to inhibition of tumor angiogenesis, progression, and metastasis. In addition, we discuss the biotransformation pathways of baicalin and baicalein, related therapeutic challenges and the future research directions to improve their bioavailability and clinical anticancer applications. Recent advances of baicalin and baicalein warrant their continued study as important natural ways for cancer interception and therapy. [Display omitted] • Natural products are reliable and powerful sources for cancer drug discovery. • Baicalin and baicalein are two major flavones isolated from Scutellaria baicalensis Georgi. • Baicalin and baicalein exhibit anticancer activities against multiple cancers with extremely low toxicity to normal cells. • Baicalin and baicalein modulate tumor stromal cells and extracellular matrix in the tumor microenvironment. • Future research needs to reveal TID and improve the bioavailability for clinical applications of baicalin and baicalein. [ABSTRACT FROM AUTHOR]

The effects of raw attapulgite clay and thermally modified attapulgite clay on the growth status of submerged plant Vallisneria Spiralis (V. spiralis) and the microenvironment of sediment were first explored. The results demonstrated that the attapulgite could effectively promote the development of V. spiralis and improve plant stress resistance by enhancing the activity of antioxidant enzymes. The 10% addition of attapulgite clay increased the biomass of V. spiralis by 27%∼174%, and the promoted rate of raw attapulgite clay was 2∼5 times of modified attapulgite clay. The attapulgite increased redox potential in sediment (P < 0.05) and provided proper niches for organism propagation, further promoting the degradation of organic matter and nutrient metabolism in sediment. The value of Shannon, Chao, and Ace was 9.98, 4865.15, 5029.08 in the 10% modified attapulgite group, and 10.12, 4856.85, 4947.78 in the 20% raw attapulgite group, respectively, indicating that the attapulgite could increase the microbial diversity and abundance in sediment. Additionally, the nutrient elements, such as Ca, Na, S, Mg, K, Zn, and Mo, that dissolved from attapulgite may also promote the V. spiralis growth. This study provided an environment-friendly approach to facilitating submerged macrophyte restoration in the eutrophic lake ecosystem. [Display omitted] • Effects of attapulgite on V. spiralis growth and sediment microenvironment. • Attapulgite can improve the sediment microenvironment. • Attapulgite can effectively promote the growth of V. spiralis. • Sediment microenvironment was important to plant growth. • Elements dissolved from attapulgite may also promote the plant growth. [ABSTRACT FROM AUTHOR]

The input of agro-pollutants, such as microplastics and nanopesticides, on farmlands is widespread and may facilitate biological invasions in agroecosystems. Here, the effects of agro-pollutants that promote invasion of congener species is studied by examining the growth performance of native Sphagneticola calendulacea and its invasive congener, S. trilobata , when grown in a native only, invasive only and mixed community. Sphagneticola calendulacea naturally occurs in croplands in southern China, while S. trilobata was introduced to this region and has since naturalized, encroaching onto farmland. In our study, each plant community was subjected to the following treatments: control, microplastics only, nanopesticides only, and both microplastics and nanopesticides. The effects of the treatments on soils of each plant community were also examined. We found that aboveground, belowground, and photosynthetic traits of S. calendulacea were significantly inhibited by the combined microplastics and nanopesticides treatment in the native and mixed communities. The relative advantage index of S. trilobata was 69.90% and 74.73% higher under the microplastics only and nanopesticides only treatments respectively compared to S. calendulacea. Soil microbial biomass, enzyme activity, gas emission rates, and chemicals in each community were reduced when treated with both microplastics and nanopesticides. Yet, soil microbial biomass of carbon and nitrogen, CO 2 emission rates and nitrous oxide rates were significantly higher (56.08%, 58.33%, 36.84% and 49.95% respectively) in the invasive species community than in the native species community under microplastics and nanopesticides. Our results suggest that the addition of agro-pollutants to soils favors the more resistant S. trilobata and suppresses the less tolerant S. calendulacea. Soil properties from the native species community are also more impacted by agro-pollutants than substrates supporting the invasive species. Future studies should explore the effects of agro-pollutants by comparing other invasive and native species and considering human activities, industry, and the soil environment. • Plant performance of invasive and native species in response to agro-pollutants. • Invasive S. trilobata had higher competitive ability in response to agro-pollutants. • Increase in soil microbial biomass in the invasive community favoured S. trilobata. • Increase in soil gas emission may increase the invasion of S. trilobata in farmlands. [ABSTRACT FROM AUTHOR]

While the associations among ambient pollutants and various pregnancy complications are well documented, the effect of ambient pollutants on intrahepatic cholestasis of pregnancy (ICP) has not been examined. This study aimed to explore the effects of ambient pollutants and sunshine duration on ICP. The study enrolled 169,971 pregnant women who delivered between 2015 and 2020 in two hospitals. The associations between ICP and exposure to ambient pollutants and sunshine duration, averaged throughout different periods (including the 3 months before conception, 1st trimester and 2nd trimester), were estimated using a generalized linear model. The interaction effects of ambient pollutants and sunshine duration on ICP were estimated. The fitted curves for ICP incidence were similar to the temporal trends of PM 2.5 , PM 10 , SO 2 , CO and NO 2 but not that of O 3. The risk of ICP was significantly elevated following a 10-μg/m3 increase in PM 2.5 (aOR [adjusted odds ratio] = 1.057, 95% CI [confidence interval]: 1.017–1.099) and PM 10 (aOR = 1.043, 95% CI: 1.013–1.074) and a 1-h decrease in sunshine duration (aOR = 1.039, 95% CI: 1.011–1.068) during the 3 months before conception. In the second trimester, a 1-μg/m3 increase in the concentration of SO 2 was associated with an increased risk of ICP (aOR = 1.011, 95% CI: 1.001–1.021). Increased concentrations of PM 2.5 and PM 10 had interactive effects with reduced sunshine duration during the 3 months before conception on increasing the risk of ICP. Exposure to PM 2.5 and PM 10 during the 3 months before conception and exposure to SO 2 in the second trimester were associated with an increased ICP risk. Reduced sunshine duration had an interactive effect with increased concentrations of PM 2.5 and PM 10 during the 3 months before conception on the occurrence of ICP. [Display omitted] • This is the first study to explore the effects of air pollutants on ICP. • Three months preconception is a sensitive exposure window for PM on ICP. • PM 2.5 and PM 10 interact with less sunshine duration to increase the risk of ICP. • Increased concentrations of SO 2 in the 2nd trimester aggregate the risk of ICP. [ABSTRACT FROM AUTHOR]

Women are vulnerable to depression during postpartum period. While several studies have shown associations between ambient air pollution exposure and depression in general population, there was few studies focused on the effect of various air pollutants on postpartum depression (PPD). This study is designed to explore the association between prenatal exposure to air pollutants and PPD, and to reveal the potential vulnerable exposure time point. The study enrolled 10,209 pregnant women who delivered between October 2019 and February 2021 in 5 participating hospitals from 3 cities in China. Edinburgh Postnatal Depression Scale (EPDS) was administered at 6 weeks postpartum to identify PPD symptoms. Associations between PPD symptoms and exposure levels in PM 2.5 , PM 10, SO 2 , CO, NO 2 , and O 3 averaged over the whole pregnancy and each trimester were estimated using logistic regression models after adjusting for potential confounding factors. Distributed lag models (DLMs) were used to determine the relevant associations in each gestational week. The risk for developing PPD symptoms was significant following a 10 μg/m3 increase in PM 10 (aOR = 1.47, 95%CI:1.36–1.59), NO 2 (aOR = 1.63, 95%CI:1.44–1.85), and 0.1 mg/m3 increase in CO (aOR = 2.31, 95%CI: 1.99–2.69) during the whole pregnancy. Similar results were also found in exposure during each trimester of pregnancy. Besides, SO 2 exposure during the second trimester was a major risk factor for developing PPD symptoms (aOR = 1.10, 95%CI:1.03–1.18). Consistent effects were also observed in DLMs, except for PM 2.5 and O 3 , which showed no significant sensitive windows throughout pregnancy period. Exposure to PM 10 , CO, NO 2 , and SO 2 in pregnancy is associated with increased risks of developing depression at 6 weeks postpartum. Our findings reveal the importance of air pollution control for preventing maternal mental health disorders among the public. [Display omitted] • Exposure to PM10, NO2 and CO in pregnancy increased risk of developing depression at 6 weeks postpartum. •The second trimester of pregnancy was the most susceptible period for developing PPD when exposed to SO2. •Prenatal exposure to multiple ambient air pollutants may contribute to development of PPD. [ABSTRACT FROM AUTHOR]