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Improvement of dye removal efficiency is beneficial to development of bioremediation for textile effluent. In this study, the effect of lignin model compounds (LMCs) and enzymatic/mild acidolysis lignin (EMAL) from rice straw as co-substrate on dye decolorization by Ganoderma lucidum EN2 were evaluated. Two azo dyes, Remazol Brilliant Violet 5R (RBV5) and Sunset Yellow (SY) were tested. Eight of the thirty tested LMCs could significantly improve both RBV5 and SY decolorization, including 3,4,5-trimethoxycinnamic acid, 4-hydroxycinnamic acid, 3,5-dimethoxy-4 -hydroxybenzaldehyde, 3-hydroxybenzoic acid, 3‑hydroxy-4-methoxycinnamic acid, guaiacol, acetosyringone, and 2,6-dimethoxyphenol. The decolorization of RBV5 (from 87.04% to 97.90%) and SY (from 62.41% to 97.40%) by G. lucidum EN2 could be efficiently enhanced in the presence of EMAL. The addition of EMAL could increase the decolorization of higher concentration of azo dyes which is more difficult to be decolorized alone. Noteworthy, laccase activity increased with the increasing amount of EMAL. EMAL showed a positive effect on fungal growth but a negligible effect on pH. These results indicated that EMAL may act as inducer to stimulate the laccase production, and the increase of laccase activity accelerated dye decolorization.

In this study, winter wheat G6PDH (TaG6PDH) and 6PGDH (Ta6PGDH) were investigated. Both their expression and their activity were upregulated under cold stress, suggesting that TaG6PDH and Ta6PGDH positively respond to cold stress in winter wheat. Exogenous abscisic acid (ABA) treatment markedly increased the expression and activity levels of TaG6PDH and Ta6PGDH in winter wheat under cold stress. Subsequently, TaG6PDH-and Ta6PGDH were overexpressed in Arabidopsis, and showed stronger reactive oxygen species (ROS)-scavenging ability and higher survival rate compared with wild-type (WT) plants under cold stress. In addition, we found that TaG6PDH and Ta6PGDH overexpression can promote the oxidative pentose phosphate pathway (OPPP) in the cytoplasm and peroxisomes of Arabidopsis. In summary, Arabidopsis overexpressing TaG6PDH and Ta6PGDH showed improved cold tolerance.

Attachment and separation of sulfate-reducing bacteria (SRB) biofilm on stainless steel (SS) in simulated cooling water with and without different sterilization treatments was investigated by calculation of surface energy, theoretical work of adhesion and analysis of Scanning Electron Microscope/Energy Dispersive Spectrometer. Two types of biocides, glutaraldehyde and Polyhexamethylene guanidine (PHMG), and electromagnetic treatment were used in this paper. The results show that PHMG had the best bactericidal performance, followed by glutaraldehyde, and electromagnetic treatment was the lowest one. The theoretical work of adhesion was used to quantitatively evaluate the adhesion of biofilm on the surface of the metal. Theoretical work of adhesion between biofilm and SS in simulated cooling water increased with time. The theoretical adhesion work and adhesive capacity of biofilm to SS surface increased after treating with glutaraldehyde while decreasing after treating with PHMG and electromagnetic field. As the theoretical adhesion work decreased, the biofilm was gradually removed from the stainless steel surface. On the contrary, the biofilm adhered more firmly. The results of SEM were also consistent with the calculation results of theoretical adhesion work. The results obtained indicated that electromagnetic treatment had the lowest effect in sterilization but the best in biofilm separation.

Dendrobine has been reported to reduce blood lipid levels and apoptosis. The present study was designed to observe the effect of dendrobine in a model of ERS using vascular endothelial cells and to reveal the biological mechanisms and pathways responsible for the therapeutic effects of dendrobine on AS. Human umbilical vein endothelial cells (HUVECs) were pre-treated with various concentrations of dendrobine, followed by treatment with tunicamycin (TM) for the establishment of the cell models of ERS. The proliferation and apoptosis of HUVECs were detected by bromodeoxyuridine staining and flow cytometry, respectively. The target binding association was verified through dual luciferase reporter assay. It was found that TM treatment resulted in a low expression of miR-381-3p. Dendrobine treatment not only promoted the proliferation, but also inhibited the apoptosis of HUVECs induced by TM. The reduced expression of 78-kDa glucose-regulated protein, inositol-requiring enzyme 1, caspase-4, C/EBP homologous protein and caspase-3 was also observed following treatment with dendrobine. Dendrobine reduced the apoptosis of endothelial cells in the model of ERS by increasing miR-381-3p expression, and partially restored the cell proliferation level. This effect was significantly reduced after the expression of miR-381-3p was blocked. On the whole, the present study demonstrated that dendrobine upregulated miR-381-3p expression to inhibit apoptosis induced by ERS in HUVECs and this process was found to be mediated by caspase-4. The findings of the present study may provide new insight into the causes of endothelial cell apoptosis during AS and reveal the potent therapeutic effects of dendrobine in AS., GRAPHICAL ABSTRACT

Enterprises are at the forefront of climate actions and multinational enterprises (MNEs) engage in foreign direct investment, allowing them substantial influence over the entire supply chain. Yet emissions embodied in the international supply chains of MNEs are poorly known. Here we trace the carbon footprints of foreign affiliates of MNEs and show that the gross volume of global carbon transfer through investment peaked in 2011, mainly driven by the decline in carbon intensity. Despite declining carbon footprints of developed country-based MNEs, there has been a notable increase in carbon transfer sourced from the Chinese mainland. We propose an investment-based accounting framework to allocate carbon footprints of MNEs to the investing country. Investment-based accounting of emissions could inform targeted and effective climate policies and actions. For instance, some large MNEs play a crucial role in carbon transfer, therefore their originating country should bear more responsibilities of carbon emission reduction as an investor. Multinational enterprises and their international supply chains can have large carbon footprints, but there is mitigation potential. Global carbon transfer through investment has declined in recent years, and this framework, assigning emissions to the investing country, would inform further action.

Calcium is not only a nutrient necessary for plant growth but also a ubiquitous central element of different signaling pathways. Ca2+ deficiency in soil may cause embryo abortion, which can eventually lead to abnormal development of peanut pods during the harvest season. To further study the mechanisms by which Ca2+ affects the shells and kernels of peanuts, transcriptome sequencing was used to explore the genes differentially expressed in shells and kernels during the early stage of peanut pod development between Ca2+ sufficient and deficient treatments. In this study, 38,894 expressed genes were detected. RNA-seq based gene expression profiling showed a large number of genes at the transcriptional level that changed significantly in shells and kernels between the Ca2+ sufficient and deficient treatments, respectively. Genes encoding key proteins involved in Ca2+ signal transduction, hormones, development, ion transport, and nutrition absorption changed significantly. Meanwhile, in the early stage of pod development, calcium first promoted nutrient absorption and development of shells, which has less effect on the formation of seed kernels. These results provide useful information for understanding the relationship between Ca2+ absorption and pod development.

Passivation of methylammonium (MA) and polyethylenimine (PEI) is introduced into the preparation process of CsPbIBr2 film. MA and PEI can precisely control the grain size and continuity of CsPbIBr2...

The presence of sulfur dioxide (SO2) in the air is a global concern because of its severe environmental and public health impacts. Recent evidence from satellite observations shows rapid changes in the spatial distribution of global SO2 emissions, but such features are generally missing in global emission inventories that use a bottom-up method due to the lack of up-to-date information, especially in developing countries. Here, we rely on the latest data available on emission activities, control measures, and emission factors to estimate global SO2 emissions for the period 1960-2014 on a 0.1° × 0.1° spatial resolution. We design two counterfactual scenarios to isolate the contributions of emission activity growth and control measure deployment on historical SO2 emission changes. We find that activity growth has been the major factor driving global SO2 emission changes overall, but control measure deployment is playing an increasingly important role. With effective control measures deployed in developed countries, the predominant emission contributor has shifted from developed countries in the early 1960s (61%) to developing countries at present (83%). Developing countries show divergency in mitigation strategies and thus in SO2 emission trends. Stringent controls in China are driving the recent decline in global emissions. A further reduction in SO2 emissions would come from a large number of developing nations that currently lack effective SO2 emission controls.

Double-seed sowing (two seeds per hole) is the dominant pattern of peanut sowing in China, but within-hole plant competition usually limits their growth and yield formation. Besides, the traditional double-seed sowing method does not facilitate mechanization during sowing. The objective of this study was to determine if single-seed sowing at a proper seeding rate yielded better than traditional double-seed sowing pattern and the differences of physiological metabolism of roots. A field experiment was conducted in two consecutive years to compare pod yields of single-seed sowing at 180 000 (S180), 225 000 (S225), and 270 000 seeds ha−1 (S270) with that of double-seed sowing at 270 000 seeds ha−1 (D270) using a completely randomized block design with four replications. And the root bleeding sap rate, nutrient content, and the main hormone contents in root bleeding sap were also comparatively investigated. Although the pod yields of single-seed sowing at the three densities were higher than that of traditional double-seed sowing (D270), S225 yielded better than the other two single-seed sowing treatments (S180 and S270). The increased pod yield in single-seed sowing at 225 000 seeds ha−1 was mainly due to the higher pod dry weight per plant and harvest index. The improved pod dry weight and shoot growth had closely relationship with the enhanced root physiological traits such as the increased root bleeding sap rate, content of free amino acids, soluble sugars, K+, Mg2+, Zn2+, and Ca2+ of the individual plant root. The improved activity of root reductive, nitrate reductase (NR) and ATPase and higher zeatin and zeatin riboside (Z+ZR) content of root bleeding sap were also crucial to the pod and shoot growth of peanut. Single-seed sowing at a moderate seeding rate (S225) is a potential practice to increase pod yield and to save seed cost.

Phosphate-solubilizing microorganisms have been considered as a novel alternative approach to provide phosphate fertilizers that promote plant growth. In this study, three strains were isolated and identified as Penicillium oxalicum FJG21, Penicillium oxalicum FJQ5, and Bacillus subtilis BPM12, with a relatively high phosphate-solubilizing activity. Various phosphate sources were investigated, and Ca3(PO4)2 was identified as the effective phosphate source. Factors governing the phosphate-solubilizing activity of the strains included carbon and nitrogen sources, initial pH, and fermentation time. A high soluble phosphorus content was achieved with 529.0 μg·mL-1, 514.0 μg·mL-1, and 330.7 μg·mL-1 for Penicillium oxalicum FJG21, Penicillium oxalicum FJQ5, and Bacillus subtilis BPM12, respectively. An inverse correlation of the quantity of soluble phosphorus content and the pH value of the medium was observed. In addition, Bacillus subtilis BPM12 displayed a prominent capability of producing indole acetic acid. Penicillium oxalicum FJG21 and Penicillium oxalicum FJQ5 exhibited high cellulase activities. These phosphate-solubilizing microorganisms with good phosphate-solubilizing capability and growth-promoting ability are the promising strains for agricultural utilization.

Smoking has become a major cause of chronic obstructive pulmonary disease through weakening of the respiratory mucus-ciliary transport system, impairing cough reflex sensitivity, and inducing inflammation. Recent researches have indicated that hydrogen sulfide is essential in the development of various lung diseases. However, the effect and mechanism of hydrogen sulfide on cigarette smoke-induced chronic obstructive pulmonary disease have not been reported. In this study, rats were treated with cigarette smoke to create a chronic obstructive pulmonary disease model followed by treatment with a low concentration of hydrogen sulfide. Pulmonary function, histopathological appearance, lung edema, permeability, airway remodeling indicators, oxidative products/antioxidases levels, inflammatory factors in lung, cell classification in bronchoalveolar lavage fluid were measured to examine the effect of hydrogen sulfide on chronic obstructive pulmonary disease model. The results showed that hydrogen sulfide effectively improved pulmonary function and reduced histopathological changes, lung edema, and permeability. Airway remodeling, oxidative stress, and inflammation were also reduced by hydrogen sulfide treatment. To understand the mechanisms, we measured the expression of TGF-β1, TGF-βIand TGF-βII receptors and Smad7 and phosphorylation of Smad2/Smad3. The results indicated that the TGF-β1 and Smad were activated in cigarette smoke-induced chronic obstructive pulmonary disease model, but inhibited by hydrogen sulfide. In conclusion, this study showed that hydrogen sulfide treatment alleviated cigarette smoke-induced chronic obstructive pulmonary disease through inhibition of the TGF-β1/Smad pathway. Impact statement COPD has become a severe public health issue in the world and smoking has become a major cause of COPD. As a result, it is a demandingly needed to explore new potential therapy for cigarette smoke-associated COPD. The present study suggested that H2S treatment improved pulmonary function and reduced histopathological changes, lung edema, permeability, inflammation, airway remodeling and oxidative injury in a COPD model induced by cigarette smoke. Although additional studies are required to elucidate the pharmacodynamics, pharmacokinetics, and pharmacology of H2S in the cigarette smoke-associated COPD, our findings provide an experimental basis for the potential clinical application of H2S in COPD treatment.

The synthesis of α-linolenic acid (ALA) requires the activity of ω-3 fatty acid desaturases (ω-3 FADs). The quality of peanut oil would be much improved if the content of ALA could be increased. A scan of the peanut genome revealed that it harbored 36 FAD genes, mapping to 16 of the species’ 20 chromosomes. A phylogenetic analysis concluded that these genes belonged to six sub-families, namely stearoyl-acyl-acyl carrier protein desaturases (SAD), FAD2, FAD3, FAD4/5, FAD6 and FAD7/8. Of these, FAD3 and FAD7/8 encoded ω-3 FADs, while genes belonging to the other four sub-families encoded ω-6 FADs. Based on RNA-Seq data, each of the 36 FAD genes was shown to be transcribed in non-stressed plants, but there was variation between them with respect to which organs they were transcribed in. Four ω-3 AhFAD3 genes were functionally characterized; when expressed in Arabidopsis thaliana protoplasts, each was localized mainly in the endoplasmic reticulum, while within peanut, the genes were more strongly transcribed in the developing seed than in either the root or the leaf. When constitutively expressed in Arabidopsis thaliana, both the total fatty acid content of the seed and the relative contribution of ALA were increased. The transgenic seedlings also exhibited an improved level of survival when challenged by salinity stress.

The selective N-monomethylation of primary anilines was realized by the use of the Me3N-BH3/N,N-dimethylformamide (DMF) system as the methyl source. This method also allows for the controllable introduction of N-CH2D, N-CHD2, and N-CD3 units with high levels of deuterium incorporation using Me3N-BH3/d7-DMF, Me3N-BD3/DMF and Me3N-BD3/d7-DMF systems, respectively.

Scavenging reactive oxygen species (ROS) by antioxidants is an important therapy to neurodegenerative diseases. In this work, a new chalcone compound (E)-3-(3,4 -dichlorophenyl)-1-(3,4-dihydroxyphenyl)-prop-2-en-1-one (A1) with potent antioxidant activity in PC12 cells was found. The MTT assay showed that A1 at 10 μM had no apparent cytotoxicity in PC12 cells. DPPH assay exhibited A1 could scavenge ROS directly. Treatment with A1 could elevate the population of viable cells in a dose-dependent manner. Furthermore, A1 protected PC12 cells against H2O2-induced apoptosis. At the molecular level, A1 conferred cytoprotection against oxidative damage in PC12 cells via up-regulation of the expression of HO-1 and GCLC proteins. These findings suggest compound A1 to be a promising antioxidant for the treatment oxidative stress-related diseases.

Asarum (Xixin), which contains analogues of aristolochic acid (AA), is the only species of the genus Aristolochia included in the Chinese Pharmacopoeia 2020. However, the contents and nephrotoxic effects of AA analogs in Asarum (Xixin) and its formulations have not been clarified. An automatic, effective solid phase extraction process and UPLC-MS/MS method were established for the pretreatment and quantitative detection of AA analogues in commercially available traditional Chinese patent medicines. The cytotoxicity and DNA damage induced by five analogues of AA were evaluated by CCK8 using human kidney cells (HK-2) and comet assays. HPLC was used to detect the analogues of AA in Asarum heterotropoides F. Schmidt (Xixin). The results showed that the contents of AA I, AA II, and AA IIIa were below the detection limit, while AA IVa and AL I presented relatively high contents of Asarum heterotropoides F. Schmidt (Xixin), within the range of 66.50–121.03 μg/g and 19.73–43.75 μg/g, respectively. The levels of AA analogues were in the nanogram-per-gram level in the main traditional Chinese patent medicines. AA I and AL I exhibited relatively high cytotoxicity at 48 h in CCK8 assays, while AA II, AA IIIa, and AA IVa showed weak cytotoxicity even at 800–1,000 μM. AA I induced significant pathological alterations and direct DNA damage at 40 mg/kg and 20 mg/kg, respectively. No distinct nephrotoxicity or hepatotoxicity was observed in mice treated with AA II, AA IIIa, AA IVa, or AL I at 40 mg/kg in this study. Consumption of Asarum heterotropoides F. Schmidt (Xixin) with controlled doses and periods is relatively safe as the contents of AA analogues in Asarum heterotropoides F. Schmidt (Xixin) and its formulations were far below those causing acute toxicity in this study. But, the long-term toxicity of Asarum heterotropoides F. Schmidt (Xixin) still needs further study.

Background With the increasing incidence of osteoporosis, vitamin K and calcium have been linked to bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC) in many studies, but the results of studies of the combined effect of vitamin K and calcium on BMD and UcOC in humans have been inconsistent. We conducted a systematic review of randomized controlled trials to assess the effect of this combination treatment on BMD and UcOC in humans. Methods A search for articles was conducted using PubMed, Embase, and the Cochrane Library database up to March 2021 (no language restrictions). We also reviewed the reference lists of the relevant publications and reviews to locate additional publications. The standard mean difference (SMD) was used as the primary measure of effect size. Our main endpoints were lumbar BMD, femoral neck BMD, hip BMD, total femoral BMD, and UcOC from baseline to end point. We performed subgroup analysis, heterogeneity testing, and assessment of publication bias. Results A total of 1346 patients from 10 randomized controlled trials were included in the meta-analysis. The forest plot analysis revealed that vitamin K combined with calcium was associated with a higher lumbar spine BMD compared to controls. The SMD was 0.20 [95% confidence interval (CI): 0.07 to 0.32]. Vitamin K and calcium supplementation led to a significant decrease in UcOC (SMD: − 1.71, 95% CI: − 2.45 to − 0.96). Subgroup analysis showed that vitamin K2 and vitamin K1 had SMDs of 0.30 (95% CI: 0.10 to 0.51) and SMDs of 0.14 (95% CI: − 0.02 to 0.29), and calcium dosages of ≤ 1000 mg/d or > 1000 mg/d had SMDs of 0.19 (95% CI: 0.05 to 0.32) and 0.26 (95% CI: − 0.04 to 0.55). Conclusion The combination of vitamin K and calcium has a positive effect on lumbar BMD and decreases the level of UcOC. Registration: The protocol for this meta-analysis was registered at the International Prospective Register of Systematic Reviews (CRD42021251825).

Previous reports demonstrated that aristolochic acids (AAs) exposure-induced nephrotoxicity, mutations, and tumorigenesis are mainly due to aristolochic acid I (AAI). Notably, the chemical structure of aristolochic acid IVa (AAIVa), which exists at higher levels in many Aristolochiaceae herbs, is extremely similar to AAI. In lack of toxicological data, it is unknown whether AAIVa exposure leads to aristolochic acid nephropathy (AAN), mutations, and tumorigenesis as of AAI. To answer these questions, mice were administered AAIVa by single or repeated long-term gavage, while AAI was used as a positive control. We found that single gavage of 40 mg/kg of AAIVa exhibited no obvious toxicity. Also, there were no tumors or death in mice administrated with 1 and 10 mg/kg of AAIVa for 6 months followed by a 12-month recovery time. There were no noteworthy alterations in gene mutation frequency in the kidney, liver, and stomach between the AAIVa and control mice. Fascinatingly, AA-associated mutational signatures, adenine-to-thymine (A>T) transversions, were absent in AAIVa-treated mice. Nonetheless, 10 mg/kg of AAIVa triggered lymphocytic infiltration and slight fibrous hyperplasia in the kidney at the 6th month; however, these were alleviated at the 12th and 18th months. On the contrary, AAI (positive control) caused severe diffuse fibrosis, tubular atrophy, necrosis, tumors in the forestomach and kidney, and death after the 6th month. It seems that long-term AAIVa exposure induced mild renal lesions could be due to the activation of the canonical or noncanonical transforming growth factor-β (TGFβ) pathway. Overall, these findings suggest that the mutagenicity and carcinogenic risk of AAIVa are very low.

The aim of the present study was to examine whether adiponectin could inhibit cardiomyocyte senescence induced by D‑galactose (D‑gal), and whether it functioned via the adiponectin receptor 1 (AdipoR1)/adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) signaling pathway. For this purpose, the expression levels of adiponectin, AdipoR1 and APPL1 in mouse plasma and myocardial tissues were detected via reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. An adiponectin‑overexpression plasmid was transfected into D‑gal‑treated H9c2 cells prior to the detection of AdipoR1 and APPL1 expression by RT‑qPCR. Senescence‑associated β‑galactose staining was then performed to observe cellular senescence following the transfection of small interfering RNAs (si) targeting AdipoR1 and APPL1 into D‑gal‑treated H9c2 cells overexpressing adiponectin. Commercial kits were used to detect reactive oxygen species (ROS) production and malondialdehyde (MDA) content in the different groups. The expression levels of heme oxygenase (HO)‑1 and high mobility group box 1 (HMGB1) were examined by western blot analysis. The results revealed that the expression levels of adiponectin, AdipoR1 and APPL1 were downregulated in aged mouse plasma, myocardial tissues and D‑gal‑treated cardiomyocytes. It was also observed that AdipoR1 and APPL1 expression levels were significantly upregulated following the overexpression of adiponectin into D‑gal‑treated cardiomyocytes. Moreover, adiponectin overexpression reduced cellular senescence induced by D‑gal and the expression of p16 and p21; these effects were reversed following transfection with si‑AdipoR1 and si‑APPL1. Adiponectin also downregulated the levels of ROS and MDA in D‑gal‑treated H9c2 cells via AdipoR1/APPL1. Additionally, the release of HO‑11/HMGB1 was affected by adiponectin via AdipoR1/APPL1, and adiponectin/AdipoR1/APPL1 suppressed ROS production via HO‑1/HMGB1. On the whole, the present study demonstrated that adiponectin played an inhibitory role in cardiomyocyte senescence via the AdioR1/APPL1 signaling pathway and inhibited the levels of oxidative stress in senescent cardiomyocytes via the HO‑1/HMGB1 signaling pathway.

Collecting near infrared (NIR) light in the rich solar spectrum is of great significance to improve the utilization of clean and renewable energy. Therefore, the design and synthesis of photocatalysts to efficiently utilize NIR have attracted wide attention of researchers. BiVO 4 :Er3+ nanofibers were synthesized by electrospinning to prepare photocatalyst with both up-conversion (UC) luminescence and photocatalytic properties. As expected, BiVO 4 :Er3+ samples show better performance than bare BiVO 4 in the process of photocatalytic degradation of Rhodamine B (RhB), and the BiVO 4 :3%Er3+ displays the highest degradation rate (95.20%) among all the samples. More importantly, the enhanced photocurrent confirms that the Er3+ ions doping is beneficial to improving the photocatalytic efficiency. This work will provide a feasible guide for the further design of photocatalysts with NIR response.

Acute renal injury (ARI) is a life-threatening condition and a main contributor to end-stage renal disease, which is mainly caused by ischemia-reperfusion (I/R). miR-106b-5p is a kidney function-related miRNA; however, whether miR-106b-5p regulates the progression of ARI remains unclear. The present study thus aimed to examine the effects of miR-106b-5p antagonist on the regulation of ARI progression. It was found that miR-106b-5p expression was upregulated in the renal tissue of rats with I/R-induced ARI and in NRK-52E rat renal proximal tubular epithelial cells subjected to hypoxia-reoxygenation (H/R). In vitro, H/R induction suppressed the proliferation, and promoted the apoptosis and autophagy of NRK-52E cells, whereas miR-106b-5p antagonist (inhibition of miR-106b-5p) promoted the proliferation, and attenuated the apoptosis and autophagy of NRK-52E cells under the H/R condition. Dual luciferase reporter gene assay validated that transcription factor 4 (TCF4) was a target of miR-106b-5p. It was further found that TCF4 overexpression promoted the proliferation, and inhibited the apoptosis and autophagy of NRK-52E cells subjected to H/R. Moreover, the effects of miR-106b-5p antagonist on NRK-52E cell proliferation, apoptosis and autophagy were mediated through the regulation of TCF4. In vivo, miR-106b-5p antagonist reduced the severity of renal injury, decreased cell proliferation in renal tissues and lowered the serum creatinine (Scr) and blood urea nitrogen (BUN) levels in the blood samples from rats with I/R-induced ARI. On the whole, the findings presented herein demonstrate that miR-106b-5p antagonist attenuates ARI by promoting the proliferation, and suppressing the apoptosis and autophagy of renal cells via upregulating TCF4.

The fluorochemical industry has shifted to the production of short chain homologues of perfluoalkyl acids (PFAAs) in recent years. Yet the effective removal of short-chain PFAAs from wastewater is still a major challenge. In this study, the removal efficiencies (RM) of short- and long-chain PFAAs emitted from two fluorochemical industrial parks were evaluated in one industrial and two domestic waste water treatment plants (WWTPs), and bioaccumulation factors (BAF) of PFAAs in various emerged and submerged aquatic plants in adjacent river and an artificial wetland were also calculated. Perfluorobutanoic acid (PFBA), perfluorobutane sulfonic acid (PFBS) and perfluorooctanoic acid (PFOA) were dominant in the whole area. The source water of the fluorochemical industrial WWTP (F-WWTP) gathered from the facilities in Park 2 contained total PFAAs (∑PFAAs) of 5,784 ng/L. Among the four main technologies, the biological aerated filter, combined with upflow sludge bed processes presented the greatest RM of ∑PFAAs in the F-WWTP, respectively. The source water of the wetland from the river brought ∑PFAAs to 21,579 ng/L, emerged plants showed higher BAF of PFBA and PFBS, while lower BAF of PFOA and PFOS than submerged plants. J. serotinus showed both the highest ∑PFAAs and the highest BAF for short chain PFAAs. With the increasing production capacity, this study provided valuable information for risk assessment and management of PFAA emission from point sources. Keywords: Fluorochemical industry, WWTP, Wetland, Aquatic plants, PFBA, PFBS

A nanoscale petal-like α-Ni(OH)2/reduced graphene oxide (α-Ni(OH)2/RGO) composite was synthesized with the one-step microwave method. α-Ni(OH)2 particles with sizes of approximately 200 nm are uniformly distributed on the reduced graphene oxide sheet in the sample. When used as an electrode for alkaline rechargeable batteries, the discharge capacity of the α-Ni(OH)2/RGO composite reaches 333.5 mAh/g at 0.2C and 247.1 mAh/g at 10 C, respectively, with an excellent rate capability. After 2000 cycles, the capacity of the electrode is insignificantly attenuated, indicating a high capacity retention and cycling stability. The outstanding electrochemical properties are attributed to the nanoscale petal-like structure α-Ni(OH)2 anchoring on the RGO sheets, which facilitates ion diffusion and increases the active surface, which is effectively reacting with the electrolyte. The nanoscale petal-like electrode material fabricated in this study provides clues to address the problem of energy applications of high-performance alkaline rechargeable batteries.

Pyrimethamine (Pyr), an antimalarial drug that targeting plasmodium dihydrofolate reductase (pDHFR), has been proved to have antitumor activity. However, its direct target on cancer cells remains unclear. Methotrexate (MTX) is a widely used anticancer drug that blocks human dihydrofolate reductase (hDHFR). In this work, we examined the anticancer effects of Pyr in vitro and in vivo. Our results showed that hDHFR and pDHFR have similar secondary and three-dimensional structures and that Pyr can inhibit the activity of hDHFR in lung cancer cells. Although Pyr and MTX can inhibit the proliferation of lung cancer cells by targeting DHFR, only Pyr can inhibit the epithelial–mesenchymal transition (EMT), metastasis and invasion of lung cancer cells. These results indicated that hDHFR is not the only target of Pyr. We further found that thymidine phosphorylase (TP), an enzyme that is closely associated with the EMT of cancer cells, is also a target protein of Pyr. The data retrieved from the Cancer Genome Atlas (TCGA) database revealed that TP overexpression is associated with poor prognosis of patients with lung cancer. In conclusion, Pyr plays a dual role in antitumor proliferation and metastasis by targeting DHFR and TP. Pyr may have potential clinical applications for the treatment of lung cancer.

Lycium ruthenicum Murray (LR) represents an agricultural cash crop found in Northwest China and has been used in traditional folk medicine for a long time. However, detailed qualitative and quantitative analyses of LR anthocyanins, as well as their pharmacological research, remain scarce. In this work, we established a rapid method for the simultaneous identification and quantification of six anthocyanidins and six anthocyanins from LR via UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS) analysis. Finally, five anthocyanidins and five anthocyanins were qualitatively and quantitatively analyzed. Among these, 10 constituents (delphinidin-3-glu, cyanidin-3-glu, petunidin-3-glu, peonidin-3-glu, malvidin-3-glu, delphinidin, cyanidin, petunidin, pelargonidin and malvidin) were detected and petunidin-3-glu proved to be the predominant species in LR. Furthermore, the anti-inflammatory effects of anthocyanin extracts and petunidin-3-glu were investigated using a rat model involving gouty arthritis induced by monosodium urate. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-18 (IL-18), prostaglandin E2 (PE2), cyclooxygenase-1 (COX-1) enzymes in serum, the paw COX-1 mRNA expression and paw volume could be determined to be significantly increased in rats suffering from gouty arthritis induced by monosodium urate. However, these indicators were found to be significantly reduced after treatment with anthocyanin extracts (200 mg/kg b.wt, p.o.) and petunidin-3-glu (40 mg/kg b.wt, p.o.). Taken in concert, our study shows that anthocyanin extracts and petunidin-3-glu may significantly reduce monosodium urate crystal-induced inflammation. Use and administration of these compounds may be potentially valuable for the further development and clinical applicability of the active compounds in this plant.

Corrosion inhibition behaviour of sodium dodecyl benzene sulphonate (SDBS) towards brass in simulated cooling water (SCW-SDBS) and Al2O3 nanofluid (SCW-SDBS-Al2O3) was investigated by electrochemical methods and surface analysis techniques. SDBS adsorbed on the brass surface and exhibited some corrosion inhibition in both media. The brass surface was covered mainly by Zn5(OH)6(CO3)2 and Cu2O in SCW, Cu2O and SDBS aggregates in SCW-SDBS, and a relatively uniform SDBS film in SCW-SDBS-Al2O3 nanofluid. Al2O3 nanoparticles and SDBS exhibited a synergistic effect of inhibiting brass corrosion due to their electrostatic adsorption and the obvious increase of critical micelle concentration of SDBS by the nanoparticles.

Lycium ruthenicum Murr. (LR) is a perennial shrub commonly used as a nutritional food and medicine. Herein, we identified 12 anthocyanins from LR, with petunidin derivatives constituting approximately 97% of the total anthocyanin content. Furthermore, the potential mechanism of anthocyanins exerting neuroprotective effects in d-galactose (d-gal)-treated rats was explored. Behavioral results showed that anthocyanins relieved d-gal-induced memory disorder. Additionally, anthocyanins reduced receptor for advanced glycation end products (RAGE) and suppressed oxidative stress caused by d-gal. Anthocyanins suppressed microgliosis and astrocytosis and reduced the overexpression of nuclear factor kappa B (NF-κB), interleukin-1-β (IL-1β), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α). Moreover, anthocyanins lowered C-jun N-terminal kinase ( p-JNK), caspase-3 levels, and the B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) ratio. Thus, anthocyanins from LR attenuated memory disfunction, neuroinflammation, and neurodegeneration caused by d-gal, possibly through the RAGE/NF-κB/JNK pathway, representing a promising, safe candidate for prevention and therapy of neurodegenerative diseases.

Quaking (QKI) is an alternative splicing factor that can regulate circRNA formation in the progression of epithelial–mesenchymal transition, but the mechanism remains unclear. High expression of QKI is correlated with short survival time, metastasis, and high clinical stage and pathology grade in hepatocellular carcinoma (HCC). Here we report that transcription of the QKI gene was activated by the Yin-Yang 1 (YY1)/p65/p300 complex, in which YY1 bound to the super-enhancer and promoter of QKI, p65 combined with the promoter, and p300 served as a mediator to maintain the stability of the complex. This YY1/p65/p300 complex increased QKI expression to promote the malignancy of HCC as well as an increased circRNA formation in vitro and in vivo. Hyperoside is one of several plant-derived flavonol glycoside compounds. Through virtual screening and antitumor activity analysis, we found that hyperoside inhibited QKI expression by targeting the YY1/p65/p300 complex. Overall, our study suggests that the regulatory mechanism of QKI depends on the YY1/p65/p300 complex and that it may serve as a potential target for treatment of HCC. Significance: These findings identify the YY1/p65/p300 complex as a regulator of QKI expression, identifying several potential therapeutic targets for the treatment of HCC.

The growth and yield of peanut are negatively affected by continuous cropping. Arbuscular mycorrhizal fungi (AMF) and calcium ions (Ca2+) have been used to improve stress resistance in other plants, but little is known about their roles in peanut seedling growth under continuous cropping. This study investigated the possible roles of the AMF Glomus mosseae combined with exogenous Ca2+ in improving the physiological responses of peanut seedlings under continuous cropping. G. mosseae combined with exogenous Ca2+ can enhance plant biomass, Ca2+ level, and total chlorophyll content. Under exogenous Ca2+ application, the Fv/Fm in arbuscular mycorrhizal (AM) plant leaves was higher than that in the control plants when they were exposed to high irradiance levels. The peroxidase, superoxide dismutase, and catalase activities in AM plant leaves also reached their maximums, and accordingly, the malondialdehyde content was the lowest compared to other treatments. Additionally, root activity, and content of total phenolics and flavonoids were significantly increased in AM plant roots treated by Ca2+ compared to either G. mosseae inoculation or Ca2+ treatment alone. Transcription levels of AhCaM, AhCDPK, AhRAM1, and AhRAM2 were significantly improved in AM plant roots under exogenous Ca2+ treatment. This implied that exogenous Ca2+ might be involved in the regulation of G. mosseae colonization of peanut plants, and in turn, AM symbiosis might activate the Ca2+ signal transduction pathway. The combination of AMF and Ca2+ benefitted plant growth and development under continuous cropping, suggesting that it is a promising method to cope with the stress caused by continuous cropping.

Rationale: The role of SLUG in epithelial-mesenchymal transition during tumor progression has been thoroughly studied, but its precise regulation remains poorly explored. Methods: The affinity purification, mass spectrometry and CO-IP were performed to identify the interaction between SLUG and ubiquitin-specific protease 5 (USP5). Cycloheximide chase assays and deubiquitination assays confirmed that the effect of USP5 on the deubiquitin of SLUG. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional regulation of E-cadherin by SLUG effected by USP5. EMT related markers was detected by western blotting and immunofluorescence. Molecular docking, SPR sensor (biacore) and co-location were detected to prove Formononetin targets USP5. Bioinformatics analysis was used to study the relation of USP5 and SLUG to malignancy degree of HCC. Cell migration, invasion in HCC cells and xenografts model in nude mouse were conducted to detect the promotion of USP5 and the inhibition of Formononetin on EMT. Results: USP5 interacts with and stabilizes SLUG to regulate its abundance through USP5 deubiquitination activities in epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC). USP5 is highly expressed and positively correlated with SLUG expression in HCC with high malignancy. Knockdown of USP5 inhibits SLUG deubiquitination and inhibits HCC cells proliferation, metastasis, and invasion, while overexpression of USP5 promotes SLUG stability and EMT in vitro and in vivo. Through virtual screening, we found that Formononetin exhibits excellent binding to USP5. Moreover, Formononetin inhibits deubiquitinating activities of USP5 to SLUG and consequently impedes the EMT and malignant progression of HCC. Conclusion: Our findings reveal that USP5 serve as a potential target for tumor intervention and provide a preliminary antitumor therapy for inhibit EMT by targeting USP5 or its interaction with SLUG in HCC.

Polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment. The coking industry is an important industrial source of PAHs. Coke production in China accounts for 67.44% of total global coke production. Tangshan, a coastal city on the Bohai Rim, contains the largest cluster of coking plants in China. Extremely high PAH emissions in Tangshan may cause long-distance cross-border pollution problems. In this study, the concentrations and sources of 16 priority PAHs in soil at a coking plant in Tangshan were determined and the risks posed by the PAHs were assessed. The PAH concentrations were generally higher in surface soil than subsurface soil, particularly near the coke oven, crude benzol, and coal blending areas. The dibenz[a,h]anthracene (DBA) concentrations were higher than the risk screening value (1500 ngg-1) but lower than the control value (15,000 ngg-1) for type II land defined in Chinese standard (GB36600-2018). The main sources of PAHs were coal combustion, the coke oven, and traffic. The PAH concentrations were higher in the ammonium sulfate, boiler room, coal blending, and coke oven areas than in the other areas. Toxic equivalent concentrations were calculated to assess the toxic and carcinogenic risks posed by PAHs. The toxic equivalent concentrations were relatively high in the boiler, crude benzol, and coal blending areas, where the toxic equivalent concentrations for the sums of seven highly carcinogenic PAHs contributed 95% of the toxic equivalent concentrations for the sums of the 16 PAHs that were analyzed. The carcinogenic risks posed to humans were therefore assessed using the concentrations of the seven highly carcinogenic PAHs. Dermal contact was found to be an important exposure pathway leading to carcinogenic risks. The carcinogenic risk posed by DBA was > 1 × 10-6 but

Atherosclerosis is the most common cause of cardiovascular disease and is accompanied by high mortality rates and a poor prognosis. Semaphorin 7A (Sema7A) and its receptor β1 integrin have been reported to participate in the development of atherosclerosis. However, the role of Sema7A and β1 integrin in endothelial cell injury and endothelial-to-mesenchymal transition (EMT) in atherosclerosis remains undetermined, to the best of our knowledge. The mRNA and protein expression levels of Sema7A and β1 integrin in HUVECs were analyzed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses, respectively. HUVECs were induced with 50 µg/ml oxidized low-density lipoprotein (ox-LDL) to establish an atherosclerosis cell model. Cell viability was measured using Cell Counting Kit-8 assay and the production of IL-1β, IL-6 and C-C motif chemokine ligand 2 was determined using ELISA. The expression levels of cell adhesion factors, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed using RT-qPCR and western blot analyses. Cell apoptosis was detected using flow cytometry and western blotting. The levels of EMT-related markers were evaluated using RT-qPCR, western blotting and immunofluorescence staining. The results of the present study revealed that the expression levels of Sema7A and β1 integrin were significantly upregulated in ox-LDL-treated HUVECs. Treatment with ox-LDL significantly decreased cell viability, and increased the levels of inflammatory and adhesion factors, the cell apoptotic rate and the expression levels of EMT-related proteins. Knockdown of Sema7A reversed the ox-LDL-induced inflammatory responses and EMT, while the overexpression of β1 integrin reversed the Sema7A-mediated inhibitory effects on ox-LDL-treated HUVECs. In conclusion, the findings of the present study indicated that Sema7A and β1 integrin may play significant roles in atherosclerosis by mediating endothelial cell injury and EMT progression.

Background We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM). Methods In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c). Results The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P 0.05). Conclusion Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.

Nitraria tangutorum Bobr. is suggested to be active in immunoregulation and antioxidation. However, the in vivo bioactivity of N. tangutorum Bobr.-derived polysaccharides (NTP) and their anti-inflammatory activity have not been addressed. In the present study, we extracted and purified polysaccharides from N. tangutorum Bobr. and determined their anti-inflammatory activities in vivo. HPGPC, UHPLC/DAD, and NMR analyses identified that the monosaccharide components of NTP were Man, Rha, GalUA, Glu, Gal, and Ara, with relative contents of 3.52%, 15.08%, 10.00%, 26.73%, 38.08%, and 6.59%, respectively. In mice with lipopolysaccharide (LPS)-induced Acute Lung Injury (ALI), NTP treatment attenuated tissue damage, inhibited the production of inflammatory cytokines, and promoted the anti-oxidative response. The supposed mechanism may be via suppressing the Toll-like receptor 4 (TLR4) signaling pathway. In conclusion, our study suggests a protective role of NTP in LPS-induced ALI by inhibiting inflammatory damage.

Increasing electrical and electronic waste have raised concerns about the potential toxicity of brominated flame retardants (BFRs) and heavy metals (HMs). However, few studies have focused on the combined effect of BFRs and HMs on microorganisms, especially denitrifying bacteria, which have an essential role in N cycles and N2O emission. Herein, we investigate the combined effect of tetrabromobisphenol A (TBBPA) and Cu on model denitrifying bacteria. A further 24.5% decline in N removal efficiency was observed when 0.05 mg/L Cu were added into a denitrifying system containing 0.75 mg/L TBBPA. Further study demonstrated that Cu heightened the toxicity of TBBPA to denitrification via following aspects: (1) Cu stimulated EPS secretion induced by TBBPA during denitrification, blocked the transmembrane transport of glucose, which caused insufficient carbon substrate for bacteria growth and electron provision; (2) Cu further suppressed key denitrifying enzymes’ activity and down-regulated genes involving electron transport induced by TBBPA, led to the decrease of electron transport activity. Finally, the decrease of bacterial growth, insufficient electron donor, and lower electron transport activity caused the synergetic toxic effect of TBBPA and Cu on denitrification. Overall, the present study provides new insights into the combined effect of BFRs and HMs on microorganisms.

A new determination method of 1-deoxynojirimycin (1-DNJ) in mulberry leaves based on ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed. Dried and crushed mulberry leaves’ sample was extracted by MeCN-water solvent, purified by graphitized carbon black (GCB) and primary secondary amine (PSA) to remove organic acids and pigments, and then analyzed after attenuation and filtration. The calibration curve showed linearity in the concentration range of 10–500 ng/mL, with the correlation coefficient of 0.998. Recoveries of spiked 1-DNJ at three fortification levels ranged from 94.6% to 96.4%, with relative standard derivation below 1.2%. Additionally, the matrix effect was assessed as negligible. Compared with methods by gas chromatography (GC) and liquid chromatography (LC) via real sample detection, the proposed method acquired better stability and detection efficiency. These results proved that this method has advantages of simple operation, complete purification, small pretreatment loss, good precision and accuracy, and high determination specificity, which is suitable for massive monitoring and precise quantitation of 1-DNJ in mulberry leaves.

In the present study, an efficient method based on ligand fishing and high-speed counter-current chromatography (HSCCC) was established to screen, enrich and separate the active components with the α-amylase inhibitory activity from a traditional dish Toona sinensis. The active components were screened from T. sinensis by ligand fishing using the magnetic immobilized α-amylase prepared through solvothermal and crosslinking methods. HSCCC was used to separate the target compound according to the K value. As a result, a potential active compound 1,2,3,4,6-penta-O-galloyl-β- d -glucose and a non-target compound quercetin-3-O-α-L-rhamnopyranoside were separated and identified. In-vitro experiments indicated that 1,2,3,4,6-penta-O-galloyl-β- d -glucose had the activity against α-amylase and the IC50 value was 93.49 ± 0.80 μg/mL which was higher than that of the non-target compound. The result further confirmed the molecular fishing effect of magnetic immobilized α-amylase. The present study can not only find and separate the hypoglycemic substances in T. sinensis quickly and effectively, but also can provide a new approach for the study of natural active components.

Long winters led to a one-crop-a-year cultivation system until the winter wheat Dongnongdongmai 1 (Dn1) was successfully cultivated in northeast China. This crop variety is resistant to extremely low temperatures (-35 °C). To better understand the adaptability of winter wheat Dn1 to low temperatures, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) and metabolomics analysis was conducted on the tillering nodes of winter wheat during the overwintering period. Enzyme-regulating genes of the metabolic products were also quantitatively analysed. The metabolomic results for the tillering nodes in the overwintering period showed that disaccharides had a strong protective effect on winter wheat Dn1. Amino acid metabolism (i.e. proline, alanine and GABA) changed significantly throughout the whole wintering process, whereas organic fatty acid metabolism changed significantly only in the late stage of overwintering. This result indicates that the metabolites used by winter wheat Dn1 differ in different overwintering stages. The relationship between field temperature and metabolite changes in winter wheat Dn1 during overwintering periods is discussed, and disaccharides were identified as the osmotic stress regulators for winter wheat Dn1 during the overwintering process, as well as maintenance of the carbon and nitrogen balance by monosaccharides, amino acids and lipids for cold resistance.

The flower of S. japonica is a favorite food and used as traditional medicine. In the present study, a facile and effective method based on the changes in the composition before and after the enzyme reaction was established to screen the active compounds from complex natural products. The separation of an active compound from the ethanolic extracts of Sophora japonica var. violacea, which exhibited the α-amylase inhibitory activity is presented as an example. The analysis of HPLC showed that one component was reduced by 25% after the enzyme reaction. The potential active compound was isolated via LH-20 gel permeation chromatography and identified as kaempferol 3-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-galactopyranosyl-7-O-α-L-rhamnopyranoside by 1H and 13C NMR. The in vitro test indicated that the compound had the α-amylase inhibitory activity, and the IC50 was 88.56 ± 0.60 μg mL−1. The molecular docking study of this compound showed that the compound enfolded in the active sites of α-amylase completely and interacted with the amino acid residues through hydrogen bonds, van der Waals force and hydrophobic interactions.

There are substantial differences in carbon footprints across households. This study applied an environmentally extended multiregional input–output approach to estimate household carbon footprints for 12 different income groups of China’s 30 regions. Subsequently, carbon footprint Gini coefficients were calculated to measure carbon inequality for households across provinces. We found that the top 5% of income earners were responsible for 17% of the national household carbon footprint in 2012, while the bottom half of income earners caused only 25%. Carbon inequality declined with economic growth in China across space and time in two ways: first, carbon footprints showed greater convergence in the wealthier coastal regions than in the poorer inland regions; second, China’s national carbon footprint Gini coefficients declined from 0.44 in 2007 to 0.37 in 2012. We argue that economic growth not only increases income levels but also contributes to an overall reduction in carbon inequality in China.

An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.

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Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice. However, the effects of repeated intake of rhein on liver function and bile acid metabolism are rarely reported. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered with rhein for 5 weeks. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), and bile salt export pump (BSEP) mRNA, and upregulated the expression of (cholesterol 7α-hydroxylase) CYP7A1 mRNA. Rhein close to the clinical dose (10 mg/kg and 30 mg/kg) reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. These results denote that rhein is relatively safe to use at a reasonable dose and timing. 30 mg/kg rhein may promote bile acid transport and reduce bile acid accumulation by upregulating the expression of FXR mRNA and Mrp3 mRNA, potentially resulting in the decrease in serum UBCAs.