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Salvia miltiorrhiza is well-known for its clinical practice in treating heart and cardiovascular diseases. Its roots used for traditional Chinese medicine materials are usually brick-red due to accumulation of red pigments, such as tanshinone IIA and tanshinone I. Here we report a S. miltiorrhiza line (shh) with orange roots. Compared with the red roots of normal S. miltiorrhiza plants, the contents of tanshinones with a single bond at C-15,16 were increased, whereas those with a double bond at C-15,16 were significantly decreased in shh. We assembled a high-quality chromosome-level genome of shh. Phylogenomic analysis showed that the relationship between two S. miltiorrhiza lines with red roots were closer than their relationship with shh. It indicates that shh could be not the mutant of an extant S. miltiorrhiza line with red roots. Comparative genomic and transcriptomic analyses showed that a 1.0kb DNA fragment was deleted in shh Sm2OGD3m. Complementation assay showed that overexpression of intact Sm2OGD3 in shh hairy roots recovered furan D-ring tanshinone accumulation. Consistently, in vitro protein assay showed that Sm2OGD3 catalyzed the conversion of cyptotanshinone, 15,16-dihydrotanshinone I and 1,2,15,16-tetrahydrotanshinone I into tanshinone IIA, tanshinone I and 1,2-dihydrotanshinone I, respectively. Thus, Sm2OGD3 functions as tanshinone 15,16-dehydrogenase and is a key enzyme in tanshinone biosynthesis. The results provide novel insights into the metabolic network of medicinally important tanshinone compounds.

Female infertility is a worldwide concern that impacts the quality of life and well-being of affected couples. Failure of embryo implantation is a major cause of early pregnancy loss, which is precisely regulated by a programed molecular mechanism. Current studies have shown that proper trophoblast adhesion and invasion are essential for embryo implantation. However, the potential regulatory mechanism involved in trophoblast adhesion and invasion is yet to be fully elucidated. KRT18 has been reported to plays a critical role in early embryonic development, but its physiological function in embryo implantation remains unclear. In the present study, we revealed that KRT18 was highly expressed in trophoblast cells and knockdown of KRT18in mouse embryos inhibited embryo adhesion reaction and implantation. In vitro experiments further showed that silencing KRT18 disturbed trophoblast migration and invasion. More importantly, we provide evidence that KRT18 directly binds to and stabilizes cell surface E-cadherin in trophoblast cells through microscale thermophoresis (MST) analysis and molecular biology experiments. In brief, our data reveal that KRT18, which is highly expressed in trophoblast cells, plays an important role in the regulation of trophoblast invasion and adhesion during embryo implantation by directly binding to E-cadherin.

The chemical footprint (ChF) can identify the harmful effects of discharged chemical pollutants, helping producers to select environmentally friendly chemicals to reduce their negative environmental impact. This paper quantified and evaluated the ChF of the wet processing of cotton fabric with data collected from a dyeing enterprise. The results showed that the discharged sodium hydroxide caused the most severe impact in terms of both human toxicity and ecotoxicity due to the extensive usage and its high toxicity. The discharged sodium carbonate and dimethyl silicone oil also had a greater environmental impact. Comprehensive evaluation of human toxicity and ecotoxicity with a multi-objective grey target decision-making model indicated that the pretreatment process had the most significant impact, followed by the finishing process and dyeing process. More attention should be paid to the pretreatment process, such as the selection of environmentally friendly textile chemicals, in order to reduce the native impacts of the wet processing of cotton fabric.

Heavy metals discharged from textile production have serious impacts on human beings and the environment. Chemical footprint (ChF) methodology is an important method in quantifying the environmental loads of discharged chemical pollutants. With the help of ChF methodology, this study used the mean impact method to assess the environmental loads of heavy metals discharged from a textile enterprise. The results showed that the ChFs of discharged heavy metals calculated based on the aquatic environment of Lake Tai and Lake Poyang were 1.43E+8L and 4.64E+8L respectively. Zinc was the largest contributor, followed by copper, lead and cadmium for the two lakes.

Objective. To explore the effect of dydrogesterone tablets combined with Zishen Yutai pills on threatened abortion in early pregnancy and pregnancy outcomes. Methods. This study retrospectively analyzed the clinical data of 100 patients with threatened abortion in early pregnancy who came to the Linhai Second People’s Hospital/Taizhou Municipal Hospital from January 13, 2021, to January 13, 2022. According to different treatment methods, 48 patients treated with progesterone injection were assigned to the control group (CG), while 52 cases with the combined therapy of dydrogesterone tablets and Zishen Yutai pills were assigned to the observation group (OG). The two groups were compared in terms of the following parameters: treatment efficacy, whole blood high shear viscosity, hematocrit (HCT), plasma fibrinogen (FIB) level, spiral artery pulsatility index (PI), uterine spiral artery blood flow resistance index (RI), lumbar and abdominal pain relief time, hemostasis time, estrogen levels, pregnancy outcomes, neonatal adverse outcomes, and incidence of adverse reactions. Results. Compared with CG, the therapeutic effect in OG was observed to be evidently better, and its pain relief time and hemostasis time in the waist and abdomen were markedly shorter. After treatment, the whole blood high shear viscosity, FIB, RI, PI, and estrogen levels of both groups improved statistically compared with those before treatment, with more significant improvements in OG compared with CG. OG was also superior to CG with markedly lower incidence of preterm birth, miscarriage, neonatal adverse outcomes, and adverse reactions and a drastically higher full-term pregnancy rate. Conclusion. Zishen Yutai pill combined with dydrogesterone tablets is of remarkable therapeutic effect in treatment of early threatened abortion, which can significantly improve clinical symptoms and pregnancy outcomes of patients, with a high safety profile, which is worthy of clinical application.

Purpose. To analyze the application value of multimodal analgesia (MMA) regimen of patient-controlled epidural analgesia (PCEA) combined with multiacupoint stimulation analgesia during the whole stage of labor analgesia in primipara. Methods. 300 primiparas with natural delivery were selected. According to the different ways of labor analgesia, they were divided into the first stage of labor active period PCEA group (group A), the whole stage of labor PCEA group (group W), and the whole stage of labor PCEA combined with multiacupoint stimulation analgesia group (group WM). The effect of MMA during the whole-labor process on maternal and infant safety was evaluated. The specific observation indicators were as follows: visual analogue scale (VAS) scores before analgesia (T0), at full opening of the uterus (T1), at the end of the second stage of labor (T2), and at the end of the third stage of labor (T3); stress response indicators at T0 and T1: epinephrine (E), norepinephrine (NE), glucose (Glu), and β-endorphin (β-EP) levels; delivery time of each stage of labor; the Apgar score of newborns at 1 and 5 min after birth; indicators of umbilical artery blood gas analysis immediately after delivery: PH value, base excess (BE), partial pressure of oxygen (PaO2), and partial pressure of carbon dioxide (PaCO2); incidence of postpartum depression (PPD) at 6 weeks after delivery. Results. At T1, T2, and T3, the VAS scores were lower in groups W and WM than in group A, and the VAS scores were lower in group WM than in group W ( P < 0.05 ). At T0, there was no significant difference in the comparison of E, NE, Glu, and β-EP levels among the three groups ( P > 0.05 ). At T1, the levels of E, NE, Glu, and β-EP were higher in the three groups than in the same group at T0, the levels of E, NE, and Glu were lower, the levels of β-EP were higher in groups W and WM than in group A, and the levels of β-EP were higher in group WM than in group W ( P < 0.05 ). Comparing the delivery time of the first stage of labor in the three groups, groups A and WM were shorter than group W ( P < 0.05 ). Comparing the delivery time of the second and third stages of labor in the three groups, there was no significant difference ( P > 0.05 ). Comparing the Apgar scores of the three groups of newborns at 1 and 5 min after birth, there was no significant difference ( P > 0.05 ). Comparing the incidence of newborn asphyxia in the three groups, there was also no significant difference ( P > 0.05 ). Comparing the PH, BE, PaO2, and PaCO2 of three groups of newborns after delivery, there were no significant differences ( P > 0.05 ). At 6 weeks after delivery, the incidence of PPD was lower in groups W (10.00%) and WM (8.00%) than in group A (20.00%) ( P < 0.05 ). Conclusion. The application of the MMA regimen of PCEA combined with multiacupoint stimulation for labor analgesia during the whole stage of labor in primipara can effectively reduce labor pain and stress response during the whole stage of labor and shorten the delivery time of the first stage of labor, the indicators of newborn Apgar score and umbilical artery blood gas analysis are not affected, and the incidence of PPD in patients is reduced, which can play a protective role for the safety of mother and infant.

Aristolochic acids (AAs) and their derivatives are present in multiple Aristolochiaceae species that have been or are being used as medicinal materials. During the past decades, AAs have received increasing attention because of their nephrotoxicity and carcinogenicity. Elimination of AAs from medicinal materials using biotechnological approaches is important for improving medication safety. However, it has not been achieved because of the limited information available on AA biosynthesis. Here, we report a high-quality, reference-grade genome assembly of the AA-containing vine Aristolochia contorta. The total size of the assembly is 209.27 Mb, and it is assembled into 7 pseudochromosomes. Synteny analysis, Ks distribution, and 4DTv suggest an absence of whole-genome duplication (WGD) events in Aristolochia contorta after the angiosperm-wide WGD. Based on genomic, transcriptomic, and metabolic data, pathways and candidate genes were proposed for benzylisoquinoline alkaloid (BIA) and AA biosynthesis in A. contorta. Five O-methyltransferase genes, including AcOMT1–3, AcOMT5, and AcOMT7, were cloned and functionally characterized. The results provide a high-quality reference genome for AA-containing species of Aristolochiaceae. They lay a solid foundation for further elucidation of AA biosynthesis and regulation and for the molecular breeding of Aristolochiaceae medicinal materials.

Purpose Capsid protein L2 is the minor capsid protein of human papillomavirus 16 (HPV16). Although L2-based vaccines were developed, the therapeutic effect of recombinant viral capsid protein L2 (rVL2) was still to be illustrated. Methods We used glucose uptake and lactate production assay to verify the inhibitory effect of rVL2 on the glucose metabolism in cervical cancer cells. Secondly, we performed gene-chip assay, RT-PCR, and Western blot to determine the role of ITGB7/C/EBPβ signaling pathway in rVL2-mediated glucose metabolism in vitro. Finally, we used an animal model to verify the function of rVL2 in cervical cancer. Results We found that rVL2 reduced glucose uptake and lactate production levels in cervical cancer cells, which caused the inhibition of cell proliferation. rVL2 decreased the expression levels of key metabolic enzymes, including GLUT1, LDHA, and ALDOA, to affect cell metabolism in cervical cancer cells by inhibiting ITGB7/C/EBPβ signaling pathway in vitro and in vivo. Conclusion These results demonstrated the vital role of rVL2 in the glycolysis-induced cell growth and proliferation via suppressing ITGB7/C/EBPβ signaling axis.

Alkaline/neutral invertases (NINVs), which irreversibly catalyze the hydrolysis of sucrose into fructose and glucose, play crucial roles in carbohydrate metabolism and plant development. Comprehensive insights into NINV genes are lacking in Salvia miltiorrhiza, a well-known traditional Chinese medicinal (TCM) plant with significant medicinal and economic value. Through genome-wide prediction, nine putative SmNINV genes, termed SmNINV1-SmNINV9, were identified. Integrated analysis of gene structures, sequence features, conserved domains, conserved motifs and phylogenetic trees revealed the conservation and divergence of SmNINVs. The identified SmNINVs were differentially expressed in roots, stems, leaves, flowers, and different root tissues. They also responded to drought, salicylic acid, yeast extract, and methyl jasmonate treatments. More importantly, computational prediction and experimental validation showed that SmNINV3 and SmNINV4 were targets of Smi-miR399, a conserved miRNA previously shown to affect Pi uptake and translocation through the cleavage of PHOSPHATE2 (PHO2). Consistently, analysis of 43 NINV genes and 26 miR399 sequences from Arabidopsis thaliana, Populus trichocarpa, Manihot esculenta, and Solanum lycopersicum showed that various AtNINV, PtNINV, MeNINV, and SlNINV genes were regulated by miR399. It indicates that the miR399-NINV module exists widely in plants. Furthermore, Smi-miR399 also cleaved SmPHO2 transcripts in S. miltiorrhiza, suggesting the complexity of NINVs, PHO2, and miR399 networks.

Stable control of the ball mill grinding process is very important to reduce energy losses, enhance operation efficiency, and recover valuable minerals. In this work, a controller for the ball mill grinding process is designed using a combination of model predictive control (MPC) with the equivalent-input-disturbance (EID) approach. MPC has been researched and applied widely as one of the multi-variable control algorithms for grinding. It is used to decouple in real time. The controller design does not deal with the disturbances directly. However, strong disturbances such as those caused by ore hardness and feed particle size exist in the ball mill grinding. EID estimates the equivalent disturbance of the grinding circuit in the control input channel and integrates this disturbance directly into the control law in order to suppress disturbances promptly and effectively. This results in good disturbance suppression performance. Simulation results demonstrate that the combination of MPC with EID for controlling the ball mill grinding circuit yields better performance in terms of disturbance rejection, rapid response, and strong robustness as compared to the performance of the MPC and proportional-integral (PI) decoupling control.

The aim of the present study was to investigate the effect of notoginsenoside Rb1 (Rb1) on the ERK and p38 MAPK pathways in primary cultured pulmonary arterial smooth muscle cells (PASMCs) exposed to hypoxia and hypercapnia, in order to elucidate the mechanism underlying the effect of Rb1 on hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV). PASMCs were isolated from Sprague-Dawley rats. The cells were divided into five groups: Normal (N), hypoxia and hypercapnia (H), RbL, RbM and RbH groups. N group cells were cultured under 5% CO2 and 21% O2. H, RbL, RbM and RbH groups were cultured under 6% CO2 and 1% O2. Prior to the hypoxia and hypercapnia exposure, RbL, RbM and RbH groups were treated with 8, 40 and 100 mg/ml Rb1 for 30 min, respectively. Phosphorylated extracellular signal-regulated kinase (P-ERK) and P-p38 protein, and ERK1/2 and p38 mRNA expression levels were detected using western blot and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses, respectively. The correlations between P-ERK protein and ERK1/2 mRNA, and between P-p38 protein and p38 mRNA were evaluated. Results of western blot and RT-PCR showed hypoxia and hypercapnia increased P-ERK and P-p38 protein, and ERK1/2 mRNA, respectively (P

Image segmentation method based on level set model has wide potential application for its excellent seg-mentation result. However its complex computing restricts its application in video segmentation. In order to improve the speed of image segmentation, this paper presents a new level set initialization method based on Chan-Vese level set model. After a simple iterative, we can separate out the outline of objects. Experiments show that the method is simple and efficient, with good separation effects. The improved Chan-Vese method can be applied in video segmentation.

Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant may play an important role in many of the processes of inflammation and fibrosis. Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress. Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders. One emerging concept is that MSCs may have paracrine, rather than a functional, roles in lung injury repair and regeneration. In the present study, we investigated bone marrow mesenchymal stem cells (BMSCs) for the treatment of bleomycin-induced pulmonary fibrosis. Our results showed that BMSCs administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. The gene expression levels of NAD(P)H: quinine oxidoreductase 1 (NQO1), gama-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), attenuated by bleomycin, were increased up to basal levels after BMSCs transplantation. BMSCs significantly increased superoxide dismutase (SOD) activity and inhibited malondialdehyde (MDA) production in the injured lung. The present study provides evidence that BMSCs may be a potential therapeutic reagent for the treatment of lung fibrosis.