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Open-cell ceramic foams are widely used as filters for the purification of molten metals due to their high permeability and high efficiency for capturing non-metallic inclusions. With the consideration of manufacture and filtration behaviour, most filters are produced by replica methods. The intrinsic multiscale porous structure requires the ceramic foams to have sufficient strength. As a consequence, different processing approaches, material compositions and characterizations are investigated. Meanwhile, to further enhance the filtration performance, the functionalization of ceramic foam filters is often conducted with surface coating. This review summarizes the processing and characteristics of ceramic foam filters (CFFs), the nature and formation of non-metallic inclusions (NMIs), the filtration mechanism and applications of CFFs. The characterization of mechanical and filtration performance, as well as the corresponding strengthening and functionalization methods are also presented.

Materials that exhibit very small dimensional changes with temperature, i.e., near-zero thermal expansion (NZTE) properties, find attractive prospects in fields such as precision instrumentation and aerospace. However, how to manually design and synthesize NZTE materials with high performance instead of laboriously exploring composition has been a long-standing challenge. In this study, based on the excellent bonding and forming abilities of metallic glass (MG), a composite with continuous regulation of thermal expansion was obtained by combining different volume ratios of MG with beta-LiAlSiO4 (beta-LAS) possessing negative thermal expansion (NTE). Interestingly, excellent NZTE performance of 0.693 and 1.587 ppm/K was achieved over the 150–700 K temperature range when the volume ratio of MG was 40% and 50%, respectively. In addition, the compressive strength of the NZTE composite reached 320 and 436 MPa for the above two ratios, respectively. The thermal shock resistance results show that the composite can withstand thermal cycling tests of not less than 80 times. The proposed strategy not only provides new NZTE materials with high performance but also facilitates a shift in the preparation of high-performance NZTE composites from laborious search to customizable design.

The development of the oxy-fuel porous media combustion technique not only takes advantage of the characteristics of porous media combustion, such as a relatively low lean-burn limit and small volume, but also dramatically facilitates carbon capture and storage. In this paper, a two-layer porous burner model is established, in which a two-temperature equation model is adopted for calculation purposes. Differences in combustion behaviour between oxy-fuel and air-fuel conditions are compared. The results show that the difference in physical properties between CO2 and air is the main reason for the significant variation of combustion behaviours under the conditions of oxy-fuel compared to air-fuel. The specific performance is lower combustion temperature and flame propagation speed. The temperature under oxy-fuel combustion conditions is 300 K lower than that under air-fuel combustion conditions at an equivalence ratio of 0.6, and the stable range of oxy-fuel combustion is only approximately 50% of air-fuel combustion. The impact of porous media material parameters on combustion behavior has been investigated. These variables include the equivalence ratio, material thermal conductivity, volume heat transfer coefficient, and extinction coefficient, while the ratio of O2/CO2 remains fixed at 0.21/0.79. The influence of these variables on the stable velocity range and temperature field is consistent, but a large difference in values occurs. Reducing the thermal resistance of the burner by adjusting the properties of the porous matrix can increase the velocity limit of stable combustion. However, even if the thermal conductivity and extinction coefficient are increased by 5 times, there will be no significant impact on the stable range. Reducing the pore size of the combustion zone by 50% will increase the stable range by over 100%.

Due to the distinct design concept, high-entropy alloys (HEAs) exhibit unusual properties and lead an emerging new field. In this work, we show that a typical face-centered cubic crystalline phase CoCrFeNiMn HEA can be readily transformed into the amorphous phase under the ultrasonic vibration treatment (UVT) at a frequency of 20000 Hz. The nanoscale hierarchical features include twins, stacking faults bands, hexagonal-close packed phase bands and even amorphous bands can be obviously identified in samples treated by different UVT energies. The dominant mechanism of ultrasonic vibration-induced amorphization is that the grain refinement promotes the formation of amorphous phases when the defect density at the grain boundaries reaches a critical level. In addition, the mechanical instability is easily induced by ultrasonic vibration at high strain rate to generate amorphous phase inside the grains. As a consequence of UVT, the HEA samples revealed significant mechanical performance improvement owing to the microstructure evolution especially the generation of amorphous phase, such as yielding strength and hardness. This rapid amorphization process provides not only a candidate strengthening mechanism for HEA, but also a novel approach to unveil the pending crystal-amorphous transition problem.

Summary: In nasopharyngeal carcinoma, deep-learning extracted signatures on MR images might be correlated with survival. In this study, we sought to develop an individualizing model using deep-learning MRI signatures and clinical data to predict survival and to estimate the benefit of induction chemotherapy on survivals of patients with nasopharyngeal carcinoma. Two thousand ninety-seven patients from three independent hospitals were identified and randomly assigned. When the deep-learning signatures of the primary tumor and clinically involved gross cervical lymph nodes extracted from MR images were added to the clinical data and TNM staging for the progression-free survival prediction model, the combined model achieved better prediction performance. Its application is among patients deciding on treatment regimens. Under the same conditions, with the increasing MRI signatures, the survival benefits achieved by induction chemotherapy are increased. In nasopharyngeal carcinoma, these prediction models are the first to provide an individualized estimation of survivals and model the benefit of induction chemotherapy on survivals.

A hybrid process combining ultrasonic injection molding and electrical discharge machining was proposed to realize the economic, high-precision, and environmental-friendliness production of glass fiber reinforced polypropylene microstructured parts. First, the prism array microstructures were processed on tungsten carbide-cobalt (WC-8 wt% Co) substrate by low-speed wire electrical discharge machining and used as the mold core. Then, the glass fiber reinforced polypropylene composite (GF/PP) was melted under ultrasonic vibration, and the surface microstructure of the mold core was replicated. The experimental results show that this method can efficiently and accurately manufacture microstructured parts, and the microstructure has a high replication rate up to 95.5%. By replicating the microstructure, the surface contact angle of GF/PP parts increased from 57.1° to 134.9°, and the wettability changed from hydrophilicity to hydrophobicity. The mechanical properties test results show that the GF/PP parts fabricated by ultrasonic injection molding had excellent mechanical properties, and the 30% GF/PP parts show the highest tensile strength of 56.9 MPa. This work provides a new option for fabricating fiber reinforced composite parts.

Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC 50 value of 0.04 ± 0.01 μM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pancreatic cancer (PC) responds weakly to conventional immunotherapy. RNA N 6 -methyladenosine (m6A) modification has an essential role in the immune response, while its potential role in PC tumor microenvironment (TME) immune cell infiltration remains unknown. In this study, we thoroughly assessed the m6A modification patterns of 472 PC samples using 19 m6A regulators, and we systematically correlated these modification patterns with TME immune cell infiltration characteristics. We also created the m6Ascore and evaluated the m6A modification patterns of individual tumors, identified three different m6A modification patterns, and explored the role of the important m6A "writer" RBM15 in the regulation of macrophage function in PC. Two independent PC cohorts confirmed that patients with higher m6Ascore showed significant survival benefit. We verified that knockdown of RBM15 has the ability to inhibit PC growth and to promote macrophage infiltration and enhance phagocytosis of PC cells by macrophages. In conclusion, m6A modifications play a non-negligible role in the formation of TME diversity and complexity in PC. We reveal that inhibition of RBM15 suppresses PC development and modulates macrophage phagocytosis, and provide a more effective immunotherapeutic strategy for PC., Competing Interests: Declaration of competing interest There is no potential conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Extensive bone loss on femur and acetabulum posed a big challenge to orthopedists in total hip revision surgeries. Impaction bone grafting (IBG) as a valuable bone preservation technique could effectively address this problem. Either IBG revision on the femoral or acetabular side was well studied, while its use on both sides in one operation was not. The aim of this study is to present the outcomes of IBG on both femoral and acetabular sides at first-time hip revision., Methods: We retrospectively reviewed 8 patients (mean follow-up of 5.8 years) undergoing first-time revision with IBG on both acetabular and femoral sides at our institution. The Paprosky classification system was used to classify bone defects. Freeze-dried allografts and cemented prostheses were used in all patients. Postoperative complications and rerevision rates were reported., Results: Five patients presented a Paprosky type IIC acetabular defect, 3 with a type IIIB, IIIA, and IIC defect, respectively. Three patients presented with a type IV femoral defect, 3 with a type IIIB defect, and 2 with a type II defect. Two patients developed complications, while one had an intraoperative femoral fracture and one had delayed wound healing. At the latest follow-up, no patient had rerevisions or operations related to the prosthesis., Conclusions: IBG in combination with cemented prosthesis is a profitable biological reconstruction revision technique that could provide satisfying midterm outcomes. We first propose the use of blood clots mixed with bone grafts for potential bone incorporation enhancement, while its specific effects need to be verified in further studies., (© 2023 Published by Elsevier Inc. on behalf of The American Association of Hip and Knee Surgeons.)

The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl 3 ) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl 3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc - axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl 3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y 3+ and its underlying mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

ROR1 and Aurora kinase were overexpressed in various cancers and essential for cell proliferation, survive and metastasis. Pharmaceutical inhibition of ROR1 and Aurora kinase abrogated the activation of downstream signaling and induced cancer cell apoptosis. Hence, ROR1 and Aurora kinase considered as attractive therapeutic targets for the development of anticancer drugs. In the present work, three series of novel 6-(imidazo[1,2-a] pyridin-6-yl)-quinazolin-4(3H)-one derivatives were designed and synthesized via bioisosterism and scaffold-hopping strategies guided by FLF-13, an Aurora kinase inhibitor we discovered earlier. Most of compounds in series 2 and series 3 showed submicromolar to nanomolar inhibitory activity against multiple cancer cell lines. More importantly, compounds 12d and 12f in series 3 showed nanomolar inhibitory activity against all test cancer cells. The most promising compound 12d exhibited potent inhibitory activity against Aurora A and Aurora B with IC 50 values of 84.41 nM and 14.09 nM, respectively. Accordingly, compounds 12d induced G2/M phase cell cycle arrest at 24 h and polyploidy at 48 h. It's worth noting that 12d also displayed inhibitory activity against ROR1 and induce cell apoptosis. Furthermore, 12d could significantly inhibit the tumor growth in SH-SY5Y xenograft model with tumor growth inhibitory rate (IR) up to 46.31 % at 10 mg/kg and 52.66 % at 20 mg/kg. Overall, our data suggested that 12d might serve as a promising candidate for the development of therapeutic agents for cancers with aberrant expression of ROR1 and Aurora kinases by simultaneously targeting ROR1 and Aurora kinase., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yanhua Fan reports financial support was provided by National Natural Science Foundation of China. Mingzhi Su reports financial support was provided by National Natural Science Foundation of China. Yanhua Fan reports financial support was provided by Department of Science and Technology of Guizhou Province. Yanhua Fan has patent pending to CN202110779355.5., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aurora A (Aurora kinase A), a critical regulator of cell mitosis, is frequently overexpressed in many malignant cancers, and has been considered as a promising drug target for cancer therapy. Likewise, Phosphatidylinositol 3-kinase alpha (PI3Kα) is also regarded as one of the most important targets in cancer therapy by mediating the cell growth and angiogenesis of various human cancers. In addition, Bromodomain-containing protein 4 (BRD4) modulates oncogene expressions of Myc, Aurora kinase and various RTKs. Recently, accumulating evidences indicated that hyperactivated or abnormally expressed Aurora A, PI3Kα or BRD4 are closely associated with drug resistance and poor prognosis of non-small cell lung cancer (NSCLC). Hence, simultaneous inhibition of Aurora A, PI3Kα, and BRD4 is expected to be a new strategy for NSCLC therapy. In this study, we performed further structure optimization of 6-(2-amino-1H-benzo[d]imidazole-6-yl)-quinazolin-4(3H) -one based on previous study to obtain a series of derivatives for discovering potential Aurora A, PI3Kα and BRD4 multi-targeted inhibitors. MTT assay showed that most of the newly synthesized compounds exhibited an evident anticancer activity against the NSCLC cells. Among them, the IC 50 values of the most potent compound 9a were 0.83, 0.26 and 1.02 μM against A549, HCC827 and H1975 cells, respectively. In addition, 9a markedly inhibited the Aurora A and PI3Kα kinase activities with IC 50 values of 10.19 nM and 13.12 nM. Compound 9a induced G2/M phase arrests and apoptosis of HCC827 cells by simultaneous inhibition of Aurora A/PI3K/ BRD4 signaling pathways. Collectively, our studies suggested that 9a might be a potential multi-targeted inhibitor for NSCLC therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The ent-kaurane diterpenoid enriched fraction (EDEF) of maize root was isolated and purified, and 10 compounds, including 4 ent-kaurane diterpenoids, were isolated and identified. We evaluated their neuroprotective properties in vitro for the first time using an H 2 O 2 -induced oxidative damage model in SH-SY5Y cells. The results showed that pretreatment with maizediterpene D, a new ent-kaurane diterpenoid isolated from the EDEF, significantly attenuated H 2 O 2 -induced apoptosis by improving cell survival, reducing ROS production and increasing mitochondrial membrane potential. Mechanistically, the neuroprotective effect of maizediterpene D was confirmed to be related to the dual activation of IGF-1R and BDNF/TrkB crosstalk pathways. Our findings suggest that the EDEF and its active constituent maizediterpene D had good neuroprotective properties and could serve as potential candidates for the development of therapeutic drugs for oxidative stress-related diseases., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Four pairs of undescribed chromane and chromene meroterpenoid scalemic mixtures (1a/1b-4a/4b), together with three pairs of known chromane meroterpenoid ones (5a/5b-7a/7b) were isolated from the twigs and leaves of Rhododendron dauricum L. Among them, 1a/1b-3a/3b and 5a/5b-7a/7b were the chromane ones derived from an intramolecular [2 + 2] cyclic addition of their respective chromene precursors, forming a 6/6/6/4 and 6/6/5/4 ring fused scaffold. The absolute configurations of the chiral center at C-15 of 2a/2b were determined by Snatzke's method, and comparing the experimental and calculated electronic circular dichroism (ECD) data. The inhibitory effects of the isolated compounds were tested against lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 macrophage cells to evaluate their anti-inflammatory activity. Compounds 4a, 4b and 6a displayed inhibitory effects on nitric oxide (NO) production, and compound 4b exhibited the obvious anti-inflammatory activity, with an IC 50 value of 6.91 ± 0.97 μM, by downregulating nuclear factor kappa B (NF-κB) and reducing the expression of inducible nitric oxide synthase (iNOS) in LPS-induced RAW264.7 cells. These results intimated that 4b could be used as a leading compound to develop anti-inflammatory drugs and is worthy of further investigated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Six pairs of enantiomeric phthalide dimers (1-6) were isolated from the rhizomes of Ligusticum chuanxiong. Their structures and absolute configurations were elucidated by NMR spectroscopy, X-ray diffraction analyses, and electronic circular dichroism calculations. Compounds (+)-1 and (-)-1 are new phthalide dimers, featuring two classes of monomeric units (a phthalide and an unusual 2,3-seco-phthalide) with an uncommon linkage (3,6'/8,3'a). Compounds (+)-2 and (-)-3 are also novel phthalide dimers that had not been reported previously. Although (-)-2 and (+)-3 have been successfully isolated in previous studies, their absolute configurations were not unambiguously determined. As for compound 4, it was reported as a racemate in one study, and one of its enantiomers was identified in a subsequent study. Herein, all enantiomeric phthalide dimers were successfully separated, and their absolute configurations were determined. The inhibitory effects of all isolates against lipopolysaccharide-induced nitric oxide production were tested using RAW264.7 cells. The results show that compounds (+)-2, (-)-2, (+)-3, (-)-3, (+)-4, (-)-4, (+)-5, (+)-6, and (-)-6 have inhibitory activities, with compound (+)-5 being the most active (IC 50 value of 4.3 ± 1.3 μM)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Three undescribed isoindoline alkaloids, (+)-(R)-3-butyl-3-ethoxyisoindolin-1-one, (+)-(3S,6S,7R)-3-butyl-6,7-dihydroxy-3-methoxy-4,5,6,7-tetrahydroisoindolin-1-one, and (-)-(3R,6S,7R)-3-butyl-6,7-dihydroxy-3-methoxy-4,5,6,7-tetrahydroisoindolin-1-one, along with nine known phthalides were isolated from a water decoction of the rhizomes of Ligusticum chuanxiong using chromatographic methods. Their structures and absolute configurations were determined by extensive spectroscopic analyses and ECD data calculations. The relaxant effects of the isolated compounds on uterine contractions induced by oxytocin were investigated using a rat uterine smooth muscle contraction model. Furthermore, the effects of riligustilide on extracellular Ca 2+ influx and intracellular Ca 2+ release were assessed using high-KCl solution-induced and oxytocin-induced uterine smooth muscle contraction in a Ca 2+ -free balanced salt solution. The results showed that all the tested phthalides had inhibitory effects on oxytocin-induced uterine smooth muscle contraction. Riligustilide, a phthalide dimer, was the most active. Further examinations indicated that riligustilide reduced uterine smooth muscle contraction by inhibiting extracellular Ca 2+ influx and intracellular Ca 2+ release., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Magnesium (Mg) and some of its alloys are considered promising biodegradable metallic biomaterials for bone implant applications. The osteogenesis effect of Mg alloys is widely reported; however, the underlying mechanisms are still not clear. In this study, pure Mg, Mg-3Zn, and Mg-2Zn-1Mn were prepared, and their degradation behavior, biocompatibility, and osteogenesis effect were systematically assessed both in vitro and in vivo. Primary rat bone marrow-derived mesenchymal stem cells (BMSCs) were used to evaluate the biocompatibility of the prepared Mg alloys, and a rat femur fracture model was used to assess the stimulating effect of these alloys on bone-tissue formation. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. Extracts of the three materials showed significant stimulating effects on osteogenic differentiation of BMSCs along with non-cytotoxicity. Implantation of Mg-2Zn-1Mn wires into the femur of rats demonstrated superior histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. Moreover, the results of both in vitro and in vivo assessments demonstrated that bone morphogenetic proteins and fibroblast growth factor receptors are involved in the stimulating effect of Mg alloys. STATEMENT OF SIGNIFICANCE: This work reports the degradation behavior, biocompatibility, and osteogenic effect of pure Mg and Mg-3Zn and Mg-2Zn-1Mn alloys in both in vitro and in vivo conditions. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. The extracts of the three materials showed a significant stimulating effect on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) along with non-cytotoxicity. Mg-2Zn-1Mn wires implanted into the femur of rats showed good histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. The results of the present study suggest that bone morphogenetic proteins (BMPs) and fibroblast growth factor receptors (FGFRs) are involved in the stimulating effect of Mg alloys on osteogenesis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest associated with this article., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Lung cancer is one of the most malignant tumors with the highest mortality and morbidity. The tubers of Bletilla striata are known as "an excellent medicine for lung diseases" in traditional Chinese medicine. This study performed a targeted study to explore compounds with anti-lung cancer activity and the molecular mechanisms using A549 cells. Eighteen bibenzyl derivatives, including four new compounds (13, 14, 16, and 18), were isolated from the tubers of B. striata. Analysis of the structure-activity relationship indicated that the cytotoxicity of the bibenzyls against A549 cells increased gradually as the number of the benzyl groups in the structures increased. Bletillain (18), an unusual benzyl polymer, was found to be the most active compound. Further flow cytometric analysis, dual-luciferase assays, real-time PCR assays, and western blot assays revealed that bletillain induced autophagy in A549 cells by regulating the Akt/GSK-3β/β-catenin signaling pathway. Beclin 1, LC3, and p62 are downstream autophagy factors of Akt, and Beclin 1 was the key autophagy factor. These results suggested that bibenzyls of B. striata play important roles in the treatment of lung cancer and provided scientific evidence illustrating why the tubers of B. striata are a suitable medicine for the treatment of lung cancer in traditional Chinese medicine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bisabolane-type sesquiterpenoids, a class of monocyclic sesquiterpenoids, are widely distributed in nature and have a variety of biological activities. To provide a reference for the further research and development of these compounds, the phytochemical and biological properties of natural bisabolane-type sesquiterpenoids (356 compounds in total) isolated between 1985 and 2020 from 24 families, primarily Compositae, Zingiberaceae, Aspergillaceae, Halichondriidae, and Aplysiidae were reviewed. In vitro and in vivo studies have indicated that antibacterial, anti-inflammatory, and cytotoxic effects are the most commonly reported pharmacological properties of bisabolane-type sesquiterpenoids. Owing to their extensive significant effects, a lot of traditional medicines containing this type of compounds have been used for a long history. Thus, bisabolane-type sesquiterpenoids are a rich source of important natural products, which show great potential for the development of new drugs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Twelve tetrahydrofuran lignans (1-12), including six new compounds (1-6), were isolated from the 70% EtOH extract of the fruits of Leonurus japonicus. Spectroscopic analyses and ECD and OR calculations were used to determine their structures. Compounds 5 and 6 were unusual alkaloidal lignans with a butyrolactam unit. Based on the beneficial effects of the fruits of L. japonicus (Chongweizi in Chinese) on the liver in traditional Chinese medicine (TCM), the hepatocyte protective activities of the isolates were studied by MTT, Hoechst 33,342 staining, and western blotting. The MTT results revealed that compounds 1, 2, 7, and 8 significantly increased the survival rates of HL-7702 cells injured by acetaminophen, with EC 50 values of 10.41 ± 0.90 μM, 19.86 ± 3.13 μM, 9.68 ± 1.93 μM, and 21.35 ± 3.58 μM, respectively. In the Hoechst 33,342 fluorescence staining, compounds 1 and 7 suppressed the apoptosis of the injured HL-7702 cells. Furthermore, the western blot analysis showed that compounds 1 and 7 increased the Bcl-2/Bax protein expression ratio and procaspase-3 protein expression, indicating that compounds 1 and 7 may exert hepatoprotective activity by regulating the mitochondrial apoptotic pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Five previously undescribed polyacetylene glucosides, namely, four C 10 - and one C 14 -acetylenes, together with three known analogues, were isolated from the florets of Carthamus tinctorius L. The structures of these novel compounds were elucidated to be (5R)-5-acetoxy-8,10,12-tetradecatriyne-1-O-β-D-glucopyranoside, (2Z)-decaene-4,6,8-triyne-1-O-β-D-glucopyranoside, (8Z)-1-[(3-O-β-D-glucosyl)-isovaleroyloxy]-8-decaene-4,6-diyne, (8Z)-decaene-1-isovaleroyloxy-4,6-diyne-10-O-β-D-glucopyranoside, and (2E,8E)-decadiene-4,6-diyne-1-O-β-D-glucopyranoside via spectroscopic and chemical methods. All of the isolated compounds were tested for cytotoxicity against cancer cell lines, antibacterial activity, and inhibitory effects on the lipopolysaccharide (LPS)-induced nitric oxide (NO) production. The results showed that (5R)-5-acetoxy-8,10,12-tetradecatriyne-1-O-β-D-glucopyranoside significantly inhibited LPS-induced NO production in RAW264.7 cells in a dose-dependent manner., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Bromodomain and PHD finger containing transcription factor (BPTF) is a multidomain protein that regulates the transcription of chromatin and is related to many cancers. Herein, we report the screening-based discovery of Cpd1, a compound with micromolar affinity to the BPTF bromodomain. Through structure-guided optimization, we synthesized a variety of new inhibitors. Among these compounds, Cpd8 and Cpd10 were highly potent and selective inhibitors, with K D values of 428 nM and 655 nM in ITC assays, respectively. The high activity was explained by the cocrystal structure of Cpd8 in complex with the BPTF bromodomain protein. Cpd8 and Cpd10 were able to stabilize the BPTF bromodomain protein in cells in a cellular thermal shift assay (CETSA). Cpd8 downregulated c-MYC expression in A549 cells. All experiments prove that these two compounds are potential BPTF inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Lanostane triterpenoids are thought to be the main underlying preclinical antitumor secondary metabolites of the genus Ganoderma. To further explore the potential cytotoxic triterpenoids from Ganoderma luteomarginatum, the ethyl acetate soluble fraction of 95% ethanolic extract was systematically studied. Twelve previously undescribed lanostane-type triterpene acids were isolated from the fruiting bodies of G. luteomarginatum, and their structures were elucidated by extensive spectroscopic analyses. Among them, 11 compounds have an unusual β-configuration for OH-15. All isolates were assessed for cytotoxic activities using three human cancer cell lines (A549, HGC-27, and SMMC-7721) and one human normal cell line (LO2). (17Z)-3β,7β,15β-Trihydroxy-11,23-dioxolanost-8,17(20)-dien-26-oate and (20E)-15β-hydroxy-3,7,11,23-tetraoxolanost-20(22)-en-26-oate exhibited significant selective cytotoxicity against HGC-27 cells and A549 cells, respectively, with IC 50 values of 6.82 ± 0.77 and 13.67 ± 1.04 μM, while 3β,7β,15β-trihydroxy-11,23-dioxolanost-8-en-26-oate inhibited the proliferation of both A549 and SMMC-7721 cells. In addition, Hoechst fluorescence 33,258 staining and Annexin V-FITC/PI double staining proved that (17Z)-3β,7β,15β-trihydroxy-11,23-dioxolanost-8,17(20)-dien-26-oate could induce apoptosis in HGC-27 cells. Furthermore, a comparison of the results in this study and previous literature demonstrated that ganoderic alcohols have stronger cytotoxicity than the corresponding derivatives of ganoderic acid in the genus Ganoderma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Fuzi, a well-known traditional Chinese medicine developed from the lateral roots of Aconitum carmichaelii Debx., has been widely used for the treatment of heart failure. In order to search for active compounds from Fuzi, a phytochemical study was performed, which resulted in the isolation of 14 aminoalcohol-diterpenoid alkaloids, including one new compound (1). Their cardioprotective effects against doxorubicin-induced toxicity in H9c2 cells were evaluated. All of the alkaloids showed cardioprotective effects in a nonmonotonic concentration-response manner, with the maximum protection rates ranging from 17.96 ± 2.93% to 98.31 ± 0.35%. Compound 5 exhibited the most potent cardioprotective activity. Taking the maximum protection rate as an indicator, the preliminary structure-activity relationship analysis indicated that the substitutions of C-1, C-13, C-15, C-16, and N and the configurations of OMe-6 and OH-15 are important structural features for the cardioprotective activities of the aminoalcohol-diterpenoid alkaloids., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive and fibrosing interstitial pneumonia of unknown cause. The main feature of IPF is a heterogeneous appearance with areas of sub-pleural fibrosis. However, the mechanism of sub-pleural fibrosis was poorly understood. In this study, our in vivo study revealed that pleural mesothelial cells (PMCs) migrated into lung parenchyma and localized alongside lung fibroblasts in sub-pleural area in mouse pulmonary fibrosis. Our in vitro study displayed that cultured-PMCs-medium induced lung fibroblasts transforming into myofibroblast, cultured-fibroblasts-medium promoted mesothelial-mesenchymal transition of PMCs. Furthermore, these changes in lung fibroblasts and PMCs were prevented by blocking TGF-β1/Smad2/3 signaling with SB431542. TGF-β1 neutralized antibody attenuated bleomycin-induced pulmonary fibrosis. Similar to TGF-β1/Smad2/3 signaling, wnt/β-catenin signaling was also activated in the process of PMCs crosstalk with lung fibroblasts. Moreover, inhibition of CD147 attenuated cultured-PMCs-medium induced collagen-I synthesis in lung fibroblasts. Blocking CD147 signaling also prevented bleomycin-induced pulmonary fibrosis. Our data indicated that crosstalk between PMC and lung fibroblast contributed to sub-pleural pulmonary fibrosis. TGF-β1, Wnt/β-catenin and CD147 signaling was involved in the underling mechanism., Competing Interests: Declaration of competing interest All the authors declared no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Seven pairs of new enantiomeric sesquiterpenoids, (+)/(-)-phaeocauline A - G [(+)/(-)-1-7], were isolated from the rhizomes of Curcuma phaeocaulis by chiral HPLC separation. Their structures, including absolute configurations, were determined by spectroscopic analyses and ECD data. The isolates were assessed for vasorelaxant, anti-platelet aggregative, and neuroprotective activities. Enantiomers (+)-1 and (-)-1 showed similar activity against abnormal platelet aggregation induced by arachidonic acid, while their C-4 epimers (+)-2 and (-)-2 were inactive, which indicated that those effects were stereoselective, but not enantioselective. Compounds (+)/(-)-3-5 exhibited vasorelaxant effects against KCl-induced contraction of rat aortic rings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A new seco-cadinane sesquiterpenoid (curcumane C, 1) and a pair of new nor-bisabolene enantiomers [(+)- and (-)-curcumane D, 2a and 2b] were isolated from C. longa. Compound 1 possesses an unusual 4,5-seco-cadinane skeleton with a tetrahydrophthalide moiety, while 2a and 2b contain an unusual 15-nor-bisabolene skeleton with a chromone core. All compounds exhibited significant vasorelaxant effects against KCl-induced contraction of rat aortic rings. Compound 1 also exhibited a vasorelaxant effect against phenylephrine-induced contraction of rat aortic rings. Meanwhile, compound 1 showed a stronger vasorelaxant effect in endothelium-intact rat aortic rings compared with endothelium-denuded rat aortic rings, indicating that vasodilation by 1 involved both endothelium-dependent and endothelium-independent pathways. Furthermore, compound 1 increased the NO content in human umbilical vein endothelial cells and its vasorelaxant effect could be attenuated by treatment with L-NAME, an endothelium NO synthase inhibitor. Thus, the underlying vasodilatory mechanisms of 1 may be mediated via abrogation of extracellular Ca 2+ influx and regulation of NO release in vascular endothelial cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The nucleus is one of the most important cellular organelles. Chitosan-grafted poly-(N-3-carbobenzyloxy-lysine) (CCL) decorated with human immunodeficiency virus-1 transactivator of transcription (TAT) can co-deliver p53 and doxorubicin into the nucleus simultaneously, such that their antitumor functions are exerted. However, TAT-CCL has been shown to have an anti-tumor effect only in vitro; the effect in vivo was unsatisfactory. Here, a unique nucleus-targeted delivery system based on amidized TAT (aTAT)-CCL with aTAT functional on the surface was designed to achieve a highly efficient nucleus-targeting gene and drug delivery system for effective cancer cell elimination in vitro and in vivo. In this delivery system, TAT is amidized to inhibit its nonspecific interactions. Confocal laser scanning microscopy observations revealed that if aTAT-CCL was incubated in pH 5.0 acetate buffer solution for 24 h before use (named aTAT-CCL-HB), more aTAT-CCL-HB entered the nucleus compared with aTAT-CCL or CCL. aTAT-CCL-HB can also achieve high gene transfection and drug delivery efficiencies and low viability in HepG2 cells. However, only aTAT-CCL achieved extensive circulation in the blood compartment and high antitumor activity in vivo. Amidization of TAT in vectors may become a promising strategy for nucleus-targeted delivery systems, especially in in vivo applications., (Copyright © 2019. Published by Elsevier B.V.)

Three new sesquiterpenoids, (+)-(1R,2S,3R,4S,5R,6S,9R)-3,11,12-trihydroxypicrotoxane-2(15)-lactone (1), (-)-(1S,2R,3S,4R,5S,6R,9S,12R)-3,11,13-trihydroxypicrotoxane-2(15)-lactone (2), and (+)-(1R,5R,6S,8R,9R)-8,12-dihydroxy-copacamphan-3-en-2-one (3), together with five known compounds, were isolated from the n-butanol soluble fraction of a 95% EtOH extract of the stems of Dendrobium nobile. Their structures were determined by extensive spectroscopic analysis. Particularly, to solve difficult stereochemical problems, electronic circular dichroism calculations, NMR data calculations, and a single-crystal X-ray diffraction were performed. Interestingly, compounds 1 and 2 were picrotoxinin-type sesquiterpenoids with an unusual C15,2-lactone ring. All new sesquiterpenoids (1-3) showed a significant neuroprotective activity against H 2 O 2 -induced oxidative damage in PC12 cells. Notably, at 25 and 50 μM, compounds 1 and 2 showed the best protective effects, even better than the positive control (vitamin E)., (Copyright © 2019. Published by Elsevier B.V.)

Magnesium (Mg) and its alloys as a type of different biodegradable materials have been used in the musculoskeletal field because of their excellent biocompatibility, biodegradability and mechanical properties similar to bone; besides, Mg could promote osteoblast differentiation in vitro and induce the formation of new bone in vivo. In the present study, we prepared the extracts of Mg-Zn-Mn alloy and examined their effects on the angiogenesis of human umbilical vein endothelial cells (HUVECs). In the present study, we prepared Mg-Zn-Mn alloy extracts of different concentrations and cultured HUVECs with these extracts. The DNA synthesis capacity, the cell viability, and the tube formation capacity of HUVECs could be significantly induced by 6.25% Mg alloy extract. In the meantime, the ratios of p-FGFR/FGFR, p-PI3K/PI3K, and p-AKT/AKT were significantly increased by 6.25% Mg alloy extract treatment, while decreased by FGFR/FGFR signaling pathway inhibitor BFJ398, indicating that 6.25% Mg alloy extract could promote the angiogenesis of HUVECs via activating FGF/FGFR signaling pathway. In conclusion, these data indicate that 6.25% Mg-Zn-Mn alloy extract induces the angiogenesis of HUVECs via FGF signaling pathway. Further in vivo experiments are needed to further confirm the present in vitro findings., (Copyright © 2019. Published by Elsevier Inc.)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that typically leads to respiratory failure and death. The cause of IPF is poorly understood. Although several environmental and occupational factors are considered as risk factors in IPF, cigarette smoking seems to be the most strongly associated risk factor. Here firstly, we treated mice with cigarette (16 mg tar, 1.0 mg nicotine in each cigarette) smoking and tried to explore the role of cigarette smoking in pulmonary fibrosis. Mice were continuously subjected to smoke for about 1 h each day (12 cigarettes per day, 5 days per week) during 40 days. Bleomycin was administrated by intraperitoneal injection at a dose of 40 mg/kg on days 1, 5, 8, 11 and 15. We found bleomycin induced pulmonary fibrosis in mice, and cigarette smoking augmented bleomycin-induced fibrosis reflected by both in fibrotic area and percentages of collagen in the lungs. Then we prepared and employed cigarette smoke extract (CSE) in cell models and found that CSE could induce the activation of p-Smad2/3 and p-Akt, as well as collagen-I synthesis and cell proliferation in lung fibroblasts and pleural mesothelial cells (PMCs). TGF-β1 signaling mediated CSE-induced PMCs migration. Moreover, in vitro studies revealed that CSE had superimposed effect on bleomycin-induced activation of TGF-β-Smad2/3 and -Akt signaling. TGF-β-Smad2/3 and -Akt signaling were further augmented by cigarette smoking in the lung of bleomycin-treated mice. Taken together, these findings represent the first evidence that cigarette smoking aggravated bleomycin-induced pulmonary fibrosis via TGF-β1 signaling., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Acute lateral patellar dislocation is a very common condition in orthopedics, especially among adolescents and physically active patients. To evaluate distinct medial patellofemoral ligament (MPFL) injury patterns and the associated knee pathology after acute lateral patellar dislocation (ALPD) using magnetic resonance imaging (MRI) studies, which is essential for the development of treatment protocols., Materials and Methods: MRI images of 74 ALPD patients were taken between January 2015 to December 2016. Images were evaluated using standardized protocols., Results: The prevalence of MPFL injury following ALPD was 97.3% (72/74 patients). Among the 72 patients with MPFL, the prevalence of Type Ⅰ injury was 26.4% (19/72). Since only bone marrow edema and a partial tear were showed on MRI of these patients, conservative treatment was given. Tear of the MPFL occurred at the patellar attachment (Type Ⅱa) in 16 patients (16/72, 22.2%), at the middle area of the ligament (Type Ⅱb) in 5 patients (5/72, 6.9%), and at the femoral attachment (Type Ⅱc) in 27 patients (27/72, 37.5%). For Type Ⅱ injuries, all patients had the surgery to reconstruct the MPFL. The prevalence of Type Ⅲ MPFL injury was 6.9% (5/72) after the surgery., Conclusion: MPFL injury of is a common sequel following ALPD. We assessed the distinct injury pattern and associated pathology of MPFL using MRI studies. A good understanding of the injury pattern and associated knee pathology of MPFL is essential in managing patients with ALPD, especially if surgical intervention is considered., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Lanostane triterpenoids are major metabolites of macrofungi from the genus Ganoderma and possess enormous substitution diversity and remarkable biological activities, especially anticancer, antioxidant, and anti-inflammatory effects. The present phytochemical investigation resulted in the isolation of nine undescribed lanostane triterpenoids and five known analogues from the fruiting bodies of Ganoderma luteomarginatum, which was first phytochemically studied by our group. Chemical structures were elucidated based on spectroscopic evidence. (5α,23E)-27-nor-lanosta-8,23-dien-3,7,25-trione and (5α,23E)-27-nor-3β-hydroxylanosta-8,23-dien-7,25-dione are undescribed triterpenoids with an unusual 27-nor-lanostane carbon skeleton. All isolates were assayed for their cytotoxic activities using four human cancer cell lines (HGC-27, HeLa, A549, and SMMC-7721) and one human normal cell line (LO2), and the structure-cytotoxicity relationships were preliminarily explored. (5α,24E)-3β-acetoxyl-26-hydroxylanosta-8,24-dien-7-one exhibited the highest cytotoxicity against HeLa and A549 cell lines, with IC 50 values of 1.29 and 1.50 μM, respectively., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recent years, the role of long non-coding RNAs (lncRNAs) in atrial fibrillation (AF) has been gradually elucidated. In the current study, we measured the expression of ten AF-related lncRNAs to do qRT-PCR analysis. LncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) was found to be significantly upregulated in AF model and Ang-II-induced mice heart. CACNA1C has been reported as a biomarker in atrial fibrillation. Here, we found that the expression pattern of CACNA1C was consistent with that of KCNQ1OT1. Electrophysiological study was conducted to demonstrate the effect of KCNQ1OT1 and CACNA1C on the Effective refractory period (ERP), interatrial conduction time (IACT), incidence of AF and AF duration of Ang-II-induced mice heart. Mechanically, KCNQ1OT1 contributed to the upregulation of CACNA1C by binding with miR-384. Furthermore, YY1 could activate the transcription of KCNQ1OT1 and CACNA1C. In conclusion, the present study revealed that YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by regulating miR-384/CACNA1C axis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pleural fibrosis is barely reversible and the underlying mechanisms are poorly understood. Pleural mesothelial cells (PMCs) which have apical-basal polarity play a key role in pleural fibrosis. Loss of cell polarity is involved in the development of fibrotic diseases. Partition defective protein (PAR) complex is a key regulator of cell polarity. However, changes of PMC polarity and PAR complex in pleural fibrosis are still unknown. In this study, we observed that PMC polarity was lost in fibrotic pleura. Next we found increased Lethal (2) giant larvae (Lgl) bound with aPKC and PAR-6B competing against PAR-3A in PAR complex, which led to cell polarity loss. Then we demonstrated that Lgl1 siRNA prevented cell polarity loss in PMCs, and Lgl1 conditional knockout (ER-Cre +/- Lgl1 flox/flox ) attenuated pleural fibrosis in a mouse model. Our data indicated that Lgl1 regulates cell polarity of PMCs, inhibition of Lgl1 and maintenance of cell polarity in PMCs could be a potential therapeutic treatment approach for pleural fibrosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is growing evidence that motherwort (Leonurus japonicus Houtt.), and Chinese patent medicines derived from motherwort, alleviate postpartum uterine subinvolution, as well as the effects on myocardial and cerebral ischemic injuries. We hypothesized that these beneficial effects of motherwort may be related to angiogenesis. To test this hypothesis, we investigated the angiogenic effects of motherwort total alkaloids and essential oil, as well as their respective primary components, on zebrafish embryos. Motherwort total alkaloids significantly increased angiogenesis in transgenic Tg (flk1: EGFP) zebrafish embryos treated with sunitinib, as did stachydrine, the most abundant alkaloid produced by motherwort. Unexpectedly, motherwort essential oil was toxic to zebrafish embryos. Our results indicated, for the first time, that motherwort alkaloids were potent angiogenic agents, while even low concentrations of motherwort essential oil were toxic. As angiogenesis is a critical aspect of postpartum recovery, our results provide evidence for traditional application of motherwort water decoction and its Chinese patent medicines (e.g. motherwort injection) to promote postpartum recovery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The crude extract and some Chinese patented medicines of Leonurus japonicus Houtt. have been proven to affect the uterine smooth muscle. L. japonicus injection is widely used in obstetric departments in China for treating postpartum hemorrhage caused by uterine inertia. Bioassay-guided isolation of the 95% EtOH extract of L. japonicus yielded four cyclopeptides, nine alkaloids, and three flavonoid glycosides, including two previously undescribed cyclopeptides, namely, cycloleonuripeptide G and cycloleonuripeptide H. The structures of the cyclopeptides were elucidated to be cyclo-(L-Phe-L-Phe-Gly-L-Pro-Gly-L-Pro) and cyclo-(L-Phe-L-Ala-L-Pro-L-Ile-L-His-Gly-L-Ala-L-Pro), respectively, via spectroscopic and chemical methods. Cyclopeptides (cycloleonuripeptides C and D) and alkaloids (imperialine-3β-D-glucoside and leonurine) promoted contraction of uterine smooth muscle strips isolated from normal rats. However, it was observed that flavonoid glycosides (spinosin, linarin, and apigenin-7-O-β-D-glucopyranoside) significantly inhibited contraction of the uterine smooth muscle strips., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Five picrotoxane sesquiterpenoids belonging to the unusual dendrobine-type (1 and 4) and the picrotoxinin-type (2, 3, and 5) were isolated from the stems of Dendrobium nobile Lindl. Their structures were established by spectroscopic analyses and physical properties. Compound 1 was a new dendrobine analogue. Although the planar structure of 2 and 3 had been reported, their absolute configurations were first determined by single-crystal X-ray diffraction and circular dichroism. Compound 2 exhibited angiogenesis effect against sunitinib-induced damage on intersegmental blood vessels in Tg (flk1: EGFP) and Tg (fli1: nEGFP) transgenic zebrafish at concentrations of 3.13, 6.25, 12.50, and 25.00μM., (Copyright © 2017. Published by Elsevier B.V.)

Pocahemiketals A and B (1 and 2), two novel hemiketal sesquiterpenoids with unprecedented skeletons, were isolated from the essential oil of the aerial parts of Pogostemon cablin. In addition to a bicyclo[3.2.1]-carbon core, 1 and 2 possessed a hemiketal α,β-unsaturated-γ-lactone moiety. Their structures were determined by extensive spectroscopic analysis, electronic circular dichroism calculation, and single-crystal X-ray diffraction. Compound 2 exhibited significant vasorelaxant activity against phenylephrine-induced contraction of a rat aorta ring with the EC 50 value of 16.32μM., (Copyright © 2017. Published by Elsevier B.V.)

Aims: To investigate the roles of salt inducible kinase (SIK1) in high glucose-induced triglyceride accumulation in human hepatoma HepG2 cells as well as in the molecular mechanism by which metformin, a drug to treat diabetes, suppresses high glucose-induced lipogenesis., Main Methods: A cell model for high glucose-induced hepatic steatosis was prepared by exposing HepG2 cells to high glucose (25mmol) in the absence or presence of metformin (0.5mmol). Intracellular triglycerides were visualized by Oil Red O and measured using a triglyceride assay kit. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. SIK1 overexpression in HepG2 cells was achieved by transient transfection, and the mRNA and protein levels of SIK1 and lipogenic factors were measured using a reverse transcription-polymerase chain reaction and western blotting, respectively., Key Findings: Lipid accumulation in HepG2 cells was obvious after treatment with high glucose for 24h. In response to high glucose, SIK1 expression was negatively correlated with that of lipogenic factors and lipid accumulation in HepG2 cells. We observed that overexpression of SIK1, or treatment with metformin, suppressed lipogenesis, even in high glucose conditions. Furthermore, treatment with metformin upregulated SIK1 mRNA and protein levels, as well as the active form of SIK1., Significance: SIK1 plays a vital role in high glucose-induced lipid accumulation, and metformin suppresses lipogenesis via the induction and activation of SIK1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ischemic heart disease is one of the most common diseases in modern society. Ischemic myocardium can be salvaged by vascular recanalization therapy, but its benefit is attenuated by injury that can occur during reperfusion. And apoptotic cell death plays an important part in myocardial ischemia-reperfusion (IR) injury. Regulator of G-protein signaling 5 (RGS5), highly expressed in different cell types of the human adult heart, is a guanosine triphosphatase-activating protein to inhibit many signaling pathways such as c-Jun NH2-terminal kinase 1/2 (JNK1/2) and p38 which promote cardiac IR-induced apoptosis. However the role of RGS5 in cardiac IR-induced apoptosis remains unclear. An in vitro IR model was applied to the isolated hearts of wild type mice (WT), RGS5-transgenic mice (TG), and RGS5-knockout mice (KO). Our results revealed that compared with either WT or KO mice, TG mice showed inhibition of cardiomyocyte apoptosis as indicated by a greater increase of B cell lymphoma/lewkmia-2 (Bcl-2), and an obvious reduction in the positive expression of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Bcl-2 Associated X protein (Bax), and active caspase-3. Moreover, the inhibition of both JNK1/2 and p38 signaling markedly reversed IR-induced cardiomyocyte apoptosis in RGS5-KO mice. These studies show that RGS5 protects cardiomyocytes against apoptosis during IR through inhibiting both JNK1/2 and p38 signaling pathways., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Six bis-spirolabdane diterpenoids along with four known analogues were isolated from the aerial parts of Leonurus japonicus. Their structures and absolute configurations were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, and a modified Mosher's method. The inhibitory activity of the compounds against the abnormal increase in platelet aggregation induced by adenosine diphosphate was investigated. Only the (13R)-bis-spirolabdane diterpenoids exhibited a significant effect., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Two new 2,4'-epoxy-8,5'-neolignans (1 and 2), together with five known 7,9';7',9-diepoxylignans (3-7), were isolated from an ethyl acetate soluble portion of a hepatoprotective water decoction of Penthorum chinese. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. This is the second report of 2,4'-epoxy-8,5'-neolignans from plants. Compounds 2, 6, and 7 showed in vitro protective activities against acetaminophen-induced hepatocyte injury at 5 μM., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Five new amino γ-butenolides, fritenolide A (1), B (2), C (3), D (4), and E (5), along with four known compounds, were isolated from the bulbs of Fritillaria unibracteata. Their structures were determined by spectroscopic analysis, including 1D NMR, 2D NMR, HRESIMS, HRESIMS/MS, IR, and CD techniques. All isolates were evaluated for the protective activity on injured hepatocytes and cytotoxic activity on human cancer cells in vitro. The unusual amino butenolides were isolated from the Liliaceae family for the first time., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Manipulation of multiple genes is a common experience in metabolic engineering and synthetic biology studies. Chromosome integration of multiple genes in one single position is always performed, however, there is so far no study on the integration of multiple genes separately in various positions (here in after referred to as "scattered integration") and its effect on fine-tuning of cellular metabolism. In this study, scattered integration of the xylose assimilation genes PsXR, PsXDH and ScXK was investigated in Saccharomyces cerevisiae, and transcription analysis of these genes as well as their enzyme activities were compared with those observed when the genes were integrated into one single site (defined as "tandem integration" here). Not only notable differences in transcription levels and enzyme activities were observed when the genes were integrated by the two strategies, but also change of the cofactor preference of PsXR gene was validated. Xylose fermentation was further studied with the strains developed with these strategies, and elevated xylose utilization rate was obtained in the scattered integration strain. These results proved that by positioning multiple genes on different chromosomes, fine-tuning of cellular metabolism could be achieved in recombinant S. cerevisiae., (Copyright © 2013 Elsevier Inc. All rights reserved.)