Tautomeric cinnamoylphloroglucinol-monoterpene adducts from Cleistocalyx operculatus and their antiviral activities.

Guided by 1H NMR spectroscopic experiments using the characteristic enol proton signals as probes, three pairs of new tautomeric cinnamoylphloroglucinol-monoterpene adducts (1-3) were isolated from the buds of Cleistocalyx operculatus. Their structures with absolute configurations were established by spectroscopic analysis, modified Mosher's method, and quantum chemical electronic circular dichroism calculation. Compounds 1-3 represent a novel class of cinnamoylphloroglucinol-monoterpene adducts featuring an unusual C-4-C-1' linkage between 2,2,4-trimethyl-cinnamyl-ß-triketone and modified linear monoterpenoid motifs. Notably, compounds 1-3 exhibited significant in vitro antiviral activity against respiratory syncytial virus (RSV).

Effect of enzymatic hydrolysis of arabinoxylan on the quality of frozen dough during the subfreezing process.

BACKGROUND: The objective of this investigation was to examine the impact of enzymatic hydrolysis of arabinoxylan (AX) on frozen dough quality under subfreezing conditions. The dough was subjected to freezing at -40 °C for 2 h and then stored at -9, -12, and -18 °C for 15 days. The water loss, freezable water content, water migration, and microstructure of the dough were measured. RESULTS: The dough containing 0.8% cellulase enzymatically hydrolyzed AX (CAX) required the shortest duration when traversing the maximum ice-crystal formation zone (6.5 min). The dough with xylanase enzymatically hydrolyzed AX (XAX) demonstrated a faster freezing rate than the dough with CAX. The inclusion of both XAX and CAX in the dough resulted in the lowest freezable water loss and reduced freezable water content and free-water content levels, whereas the inclusion of xylanase-cellulase combined with enzymatically hydrolyzed AX resulted in higher free-water content levels. The textural properties of the subfreezing temperature dough were not significantly different from the dough stored at -18 °C and sometimes even approached or surpassed the quality observed in the control group rather than the dough stored at -18 °C. In addition, the gluten network structure remains well preserved in XAX- and CAX-containing doughs with minimal starch damage. CONCLUSION: The enzymatic hydrolysis of AX from wheat bran can be used as a useful additive to improve the quality of frozen dough. © 2024 Society of Chemical Industry.

[Two new benzoyl-sesquiterpenes from Mesona chinensis].

Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.

Biomimetic Synthesis of an Antiviral Cinnamoylphloroglucinol Collection from Cleistocalyx operculatus: A Synthetic Strategy Based on Biogenetic Building Blocks.

A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A-F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels-Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D-F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153).

Discovery and Biomimetic Synthesis of a Polycyclic Polymethylated Phloroglucinol Collection from Rhodomyrtus tomentosa.

Inspired by a previously reported biomimetic synthesis study, four new naturally occurring phloroglucinol trimers 1-4 with unusual 6/5/5/6/6/6-fused hexacyclic ring systems, along with two known analogues (5 and 6) and two known biogenetically related dimers (10 and 11), were isolated from Rhodomyrtus tomentosa. Their structures and absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism calculation. By mimicking two potentially alternative biosynthetic pathways, the first asymmetric syntheses of 1-4 and the racemic syntheses of 5 and 6 were achieved in only five to six steps without the need for protecting groups. Furthermore, phloroglucinol dimers 10 and 11 exhibited significant in vitro antiviral activity against the respiratory syncytial virus.

Luminescent Two-Dimensional Metal-Organic Framework Nanosheets with Large π-Conjugated System: Design, Synthesis, and Detection of Anti-Inflammatory Drugs and Pesticides.

Two-dimensional (2D) metal-organic framework (MOF) nanosheets, with largely exposed surface area and highly accessible active sites, have emerged as a novel kind of sensing material. Here, a luminescent 2D MOF nanosheet was designed and synthesized by a facile top-down strategy based on a three-dimensional (3D) layered MOF {[Zn(H2L)(H2O)2]·H2O}n (Zn-MOF; H4L = 3,5-bis(3',5'-dicarboxyphenyl)-1H-1,2,4-triazole). With a large π-conjugated system and rigid planar structure, ligand H4L was elaborately selected to construct the bulk Zn-MOF, which can be readily exfoliated into 2D nanosheets, owing to the weak interlayer interactions and easy-to-release H2O molecules in the interspaces of 2D layers. Given the great threat posed to the ecological environment by anti-inflammatory drugs and pesticides, the developed luminescent Zn-MOF nanosheets were utilized to determine these organic pollutants, achieving highly selective and sensitive detection of diclofenac sodium (DCF) and tetramethylthiuram disulfide (TMTD). Compared to the detection limits of 3D Zn-MOF (7.72 ppm for DCF, 6.01 ppm for TMTD), the obviously lower detection limits for 2D Zn-MOF nanosheets toward DCF (0.20 ppm) and TMTD (0.18 ppm) further revealed that the largely exposed surface area with rigid planar structure and ultralarge π-conjugated system greatly accelerated electron transfer, which brought about a vast improvement in response sensitivity. The remarkable quenching performance for DCF and TMTD stems from a combined effect of photoinduced electron transfer and competitive energy absorption. The possible sensing mechanism was systematically investigated by the studies of powder X-ray diffraction, UV-vis, luminescence lifetime, and density functional theory calculations.

Quassinoids from the Roots of Eurycoma longifolia and Their Anti-Proliferation Activities.

A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 µM.

Macrocyclic Diterpenoids from Euphorbia helioscopia and Their Potential Anti-inflammatory Activity.

Guided by 1H NMR spectroscopic experiments using the aromatic protons as probes, 11 macrocyclic diterpenes (1-11) were isolated from the aerial parts of Euphorbia helioscopia. Their full three-dimensional structures, including absolute configurations, were established unambiguously by spectroscopic analysis and single-crystal X-ray crystallographic experiments. Among the isolated compounds, compound 1 is the third member thus far of a rare class of Euphorbia diterpenes featuring an unusual 5/10 fused ring system, and 2-4 are new jatrophane diterpenes. Based on the NMR data of the jatrophane diterpenes obtained in this study as well as those with crystallographic structures reported in the literature, the correlations of the chemical shifts of the relevant carbons and the configurations of C-2, C-13, and C-14 of their flexible macrocyclic ring were considered. Moreover, the anti-inflammatory activities of 1-11 were investigated by monitoring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Compound 1 showed an IC50 of 7.4 ± 0.6 µM, which might be related to the regulation of the NF-κB signaling pathway by suppressing the translocation of the p65 subunit and the consequent reduction of IL-6 and TNF-α secretions.

The concomitant apoptosis and EMT underlie the fundamental functions of TGF-ß.

TGF-ß's multipotent cellular effects and their relations are critical for TGF-ß's pathophysiological functions. However, these effects may appear to be paradoxical in understanding TGF-ß's functions. Apoptosis and epithelial-mesenchymal transition (EMT) are two fundamental events that are deeply linked to various physiological and disease-related processes. These two major cellular fates are subtly regulated and can be potently stimulated by TGF-ß, which profoundly contribute to the biological roles of TGF-ß. Moreover, these two events are also indirectly and directly correlated with TGF-ß-mediated growth inhibition and are relevant to the current understanding of the roles of TGF-ß in tumorigenesis and cancer progression. Although TGF-ß-induced apoptosis and EMT can be singly independent cellular events, they can also be mutually exclusive but interrelated concomitant events in various cases. Thus, the modulation of apoptosis and EMT is essential for the seemingly paradoxical functions of TGF-ß. However, the concomitant effect of TGF-ß on apoptosis and EMT, the balance and regulated alterations of them are still been ignored or underestimated. This review focuses on the TGF-ß-induced concomitant apoptosis and EMT. We aim to provide an insight in understanding their significance, balance, and modulation in TGF-ß-mediated biological functions.

Conversion of Ginsenoside Rb1 into Six Types of Highly Bioactive Ginsenoside Rg3 and Its Derivatives by FeCl3 Catalysis.

Ginsenoside Rb1 is an important saponin of ginseng(s); however, Rb1, with 3-O- and 20-O-sugar moieties, has low bioavailability. Here, we report the derivatization of ginsenoside Rb1 to completely generate six types of highly bioactive minor ginsenoside Rg3 and its derivatives by FeCl3 catalysis, the reaction conditions are similar to enzymatic reaction conditions. In FeCl3 catalysis, the only 20-O-sugar-moiety of ginsenoside Rb1 was decomposed into the minor ginsenosides Rk1 and Rg5 with newly produced C-20 ethylene bands; but also hydrolyzed into 20(S)-Rg3 and 20(R)-Rg3; subsequently the C-24(25) ethylene bands of 20(S)-Rg3 and 20(R)-Rg3 were hydrated to 20(S)-25-OH-Rg3 and 20(R)-25-OH-Rg3. After separation of reaction mixture from 34 g ginsenoside-Rb1 by silica-gel-column, the 3.3 g sample I of TLC top-band consisting of Rg5 and Rk1, 8.7 g sample II of TLC middle-band consisting of 20(S)-Rg3 and 20(R)-Rg3, 3.5 g sample III of TLC bottom-band consisting of unknown product-I and -II including 20(S)-25-OH-Rg3, were obtained. The sample III consisting of unknown product-I and -II was purified by crystallization, and identified to 20(S)-25-OH-Rg3 and 20(R)-25-OH-Rg3 by HPLC-Evaporative Light Scattering Detector (ELSD) and NMR. Therefore, six types of minor-ginsenosides Rk1, Rg5, 20(S)-Rg3, 20(R)-Rg3, 20(S)-25-OH-Rg3 and 20(R)-25-OH-Rg3 were successfully prepared from ginsenoside Rb1 by FeCl3 catalysis. FeCl3 has low toxicity and is inexpensive, and the reaction conditions are similar to enzymatic reaction conditions; thus, this method is applicable to the development of ginseng-based drugs.

Tomentodione E, a new sec-pentyl syncarpic acid-based meroterpenoid from the leaves of Rhodomyrtus tomentosa.

A new meroterpenoid, tomentodione E (1), along with four known ones (2-5) were isolated from the leaves of Rhodomyrtus tomentosa. Their structures were elucidated based on extensive spectroscopic data as well as computational methods. Compound 1 represents the first example of meroterpenoid possessing a sec-pentyl syncarpic acid motif coupled with a caryophyllene. Compounds 1-4 were evaluated for their in vitro antiviral activity against respiratory syncytial virus (RSV) with cytopathic effect (CPE) reduction assay, and 2 showed potent in vitro anti-RSV effect.

TUFM downregulation induces epithelial-mesenchymal transition and invasion in lung cancer cells via a mechanism involving AMPK-GSK3ß signaling.

Mitochondrial dysfunction and epithelial-to-mesenchymal transition (EMT) play important roles in cancer development and metastasis. However, very little is known about the connection between mitochondrial dysfunction and EMT. Tu translation elongation factor, mitochondrial (TUFM), a key factor in the translational expression of mitochondrial DNA, plays an important role in the control of mitochondrial function. Here, we show that TUFM is downregulated in human cancer tissues. TUFM expression level was positively correlated with that of E-cadherin and decreased significantly during the progression of human lung cancer. TUFM knockdown induced EMT, reduced mitochondrial respiratory chain activity, and increased glycolytic function and the production of reactive oxygen species (ROS). Mechanistically, TUFM knockdown activated AMPK and phosphorylated GSK3ß and increased the nuclear accumulation of ß-catenin, leading to the induction of EMT and increased migration and metastasis of A549 lung cancer cells. Although TUFM knockdown also induced EMT of MCF7 breast cancer cells, the underlying mechanism appeared somewhat different from that in lung cancer cells. Our work identifies TUFM as a novel regulator of EMT and suggests a molecular link between mitochondrial dysfunction and EMT induction.

Hepatocyte nuclear factor 6 suppresses the migration and invasive growth of lung cancer cells through p53 and the inhibition of epithelial-mesenchymal transition.

Epithelial-mesenchymal transition plays an important role in many patho-physiological processes, including cancer invasion and metastatic progression. Hepatocyte nuclear factor 6 (HNF6) has been known to be an important factor for both physiological and pathological functions in liver and pancreas. However, its role in EMT and lung cancer progression remains unidentified. We observed that HNF6 level can be down-regulated by TGF-ß1 in human lung cancer cells. Knockdown of HNF6 induced EMT and increased cell migration. In contrast, ectopically expression of HNF6 inhibited cell migration and attenuated TGF-ß1-induced EMT. The data suggest that HNF6 plays a role in maintaining epithelial phenotype, which suppresses EMT. HNF6 also inhibits both colony formation and proliferation of lung cancer cells. It pronouncedly reduced the formation of tumor xenografts in nude mice. In addition, HNF6 can activate the promoter activity of p53 by directly binding to a specific region of its promoter and therefore increase the protein level of tumor suppressor p53. p53 knockdown induced EMT and increased cell migration, whereas the opposite effect was generated by p53 overexpression. p53 knockdown also inhibited the effect of HNF6 on EMT and cell migration, indicating that p53 is required for the functions of HNF6 herein. Moreover, there is a high positive correlation among the expression levels of HNF6, p53, and E-cadherin in human lung cancer cells and tissues. The data suggest that HNF6 inhibits EMT, cell migration, and invasive growth through a mechanism involving the transcriptional activation of p53.

[Experimental study on promotion of peripheral nerve regeneration by selenium-methylselenocysteine].

Objective: To investigate the feasibility of selenium-methylselenocysteine (SMC) to promote peripheral nerve regeneration and its mechanism of action. Methods: Rat Schwann cells RSC96 cells were randomly divided into 5 groups, which were group A (without any treatment, control group), group B (adding 100 µmol/L H 2O 2), group C (adding 100 µmol/L H 2O 2+100 µmol/L SMC), group D (adding 100 µmol/L H 2O 2+200 µmol/L SMC), group E (adding 100 µmol/L H 2O 2+400 µmol/L SMC); the effect of SMC on cell proliferation was detected by MTT method, and the level of oxidative stress was detected by immunofluorescence for free radicals [reactive oxygen species (ROS)] after determining the appropriate dose group. Thirty-six 4-week-old male Sprague Dawley rats were randomly divided into 3 groups, namely, the sham operation group (Sham group), the sciatic nerve injury group (PNI group), and the SMC treatment group (SMC group), with 12 rats in each group; the rats in the PNI group were fed with food and water normally after modelling operation, and the rats in the SMC group were added 0.75 mg/kg SMC to the drinking water every day. At 4 weeks after operation, the sciatic nerves of rats in each group were sampled for neuroelectrophysiological detection of highest potential of compound muscle action potential (CMAP). The levels of inflammatory factors [interleukin 17 (IL-17), IL-6, IL-10 and oxidative stress factors catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)] were detected by ELISA assay. The luxol fast blue (LFB) staining was used to observe the myelin density, fluorescence intensity of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) was observed by immunofluorescence staining, and myelin morphology was observed by transmission electron microscopy with measurement of axon diameter. Western blot was used to detect the protein expressions of p38 mitogen-activated protein kinases (p38MAPK), phosphorylated p38MAPK (p-p38MAPK), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Results: MTT assay showed that the addition of SMC significantly promoted the proliferation of RSC96 cells, and the low concentration could achieve an effective effect, so the treatment method of group C was selected for the subsequent experiments; ROS immunofluorescence test showed that group B showed a significant increase in the intensity of ROS fluorescence compared with that of group A, and group C showed a significant decrease in the intensity of ROS fluorescence compared with that of group B ( P<0.05). Neuroelectrophysiological tests showed that the highest potential of CMAP in SMC group was significantly higher than that in PNI and Sham groups ( P<0.05). ELISA assay showed that the levels of IL-6, IL-17, and MDA in PNI group were significantly higher than those in Sham group, and the levels of IL-10, SOD, and CAT were significantly lower; the levels of IL-6, IL-17, and MDA in SMC group were significantly lower than those in PNI group, and the levels of IL-10, SOD, and CAT were significantly higher ( P<0.05). LFB staining and transmission electron microscopy showed that the myelin density and the diameter of axons in the SMC group were significantly higher than those of the PNI group and the Sham group ( P<0.05). Immunofluorescence staining showed that the fluorescence intensity of GFAP and MBP in the SMC group were significantly stronger than those in the PNI group and Sham group ( P<0.05). Western blot showed that the relative expressions of Nrf2 and HO-1 proteins in the SMC group were significantly higher than those in the PNI group and Sham group, and the ratio of p-p38MAPK/p38MAPK proteins was significantly higher in the PNI group than that in the SMC group and Sham group ( P<0.05). Conclusion: SMC may inhibit oxidative stress and inflammation after nerve injury by up-regulating the Nrf2/HO-1 pathway, and then inhibit the phosphorylation of p38MAPK pathway to promote the proliferation of Schwann cells, which ultimately promotes the formation of myelin sheaths and accelerates the regeneration of peripheral nerves.

Anti-inflammatory naphthoquinone-monoterpene adducts and neolignans from Eugenia caryophyllata.

A phytochemical investigation on the buds of edible medicinal plant, Eugenia carvophyllata, led to the discovery of seven new compounds, caryophones A-G (1-7), along with two biogenetically-related known ones, 2-methoxy-7-methyl-1,4-naphthalenedione (8) and eugenol (9). Compounds 1-3 represent the first examples of C-5-C-1' connected naphthoquinone-monoterpene adducts with a new carbon skeleton. Compounds 4-7 are a class of novel neolignans with unusual linkage patterns, in which the C-9 position of one phenylpropene unit coupled with the aromatic core of another phenylpropene unit. The chemical structures of the new compounds were determined based on extensive spectroscopic analysis, X-ray diffraction crystallography, and quantum-chemical calculation. Among the isolates, compounds (-)-2, 3, 6, and 9 showed significant in vitro inhibitory activities against respiratory syncytial virus (RSV)-induced nitric oxide (NO) production in RAW264.7 cells.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.

TMEPAI regulates EMT in lung cancer cells by modulating the ROS and IRS-1 signaling pathways.

The epithelial-mesenchymal transition (EMT) has been implicated in various pathophysiological processes, including cancer cell migration and distal metastasis. Reactive oxygen species (ROS) and insulin receptor substrate-1 (IRS-1) are important in cancer progression and regulation of EMT. To explore the biological significance and regulatory mechanism of EMT, we determined the expression, the biological function and the signaling pathway of prostate transmembrane protein, androgen induced-1 (TMEPAI), during the induction of EMT and cell migration. Transforming growth factor (TGF)-ß1 significantly upregulated the expression of TMEPAI during EMT in human lung adenocarcinoma. Depletion of TMEPAI abolished TGF-ß1-induced downregulation of ferritin heavy chain and the subsequent generation of ROS, thus suppressing TGF-ß1-induced EMT and cell migration. In addition, increased ROS production and overexpression of TMEPAI downregulated the level of IRS-1. Both the addition of H2O2 and IRS-1 small interfering RNA rescued the ability of TGF-ß1 to induce EMT in TMEPAI-depleted cells. Remarkably, the levels of TMEPAI in lung tumor tissues are very high, whereas its expression in normal lung epithelium is very low. Moreover, TMEPAI expression was positively correlated with the cell mesenchymal phenotype and migration potential. Our work reveals that TMEPAI contributes to TGF-ß1-induced EMT through ROS production and IRS-1 downregulation in lung cancer cells.

Age-related changes in cellular electrophysiology and calcium handling for atrial fibrillation.

This study was to investigate whether or not the dysfunction of atrial repolarization and abnormality of the intracellular Ca(2+) handling protein was augmented with ageing. Four groups of dogs were studied, adult and aged dogs in sinus rhythm (SR) and atrial fibrillation (AF) induced by rapid atrial pacing. We used whole cell patch clamp recording techniques to measure L-type Ca(2+) current in cardiomyocytes dispersed from the left atria. Expressions of the Ca(2+) handling protein were measured by real-time quantitative reverse transcription-polymerase chain reaction and Western blot methods. Cardiomyocytes from old atria showed longer action potential (AP) duration to 90% repolarization, lower AP plateau potential and peak L-type Ca(2+) current densities at both age groups in SR. AF led to a higher maximum diastolic potential, an increase of amplitude of phase 0, decreases of AP duration to 90% repolarization, plateau potential and peak L-type Ca(2+) current densities. Compared to the adult group, mRNA and protein expressions of the L-type calcium channel a1c were decreased, whereas expressions of calcium adenosine triphosphatase were increased in the aged group. Compared to SR group, expressions of Ca(2+) handling protein except for phospholamban were significantly decreased in both age groups with AF. We conclude that these ageing-induced electrophysiological and molecular changes showed that general pathophysiological adaptations might provide a substrate conducive to AF.

Retinoic acid regulates bone morphogenic protein signal duration by promoting the degradation of phosphorylated Smad1.

The proper function of the bone morphogenic protein (BMP) pathway during embryonic development and organ maintenance requires its communication with other signaling pathways. Unlike the well-documented regulation of the BMP pathway by FGF/MAPK and Wnt/GSK3 signals, cross-talk between BMP/Smad and retinoic acid (RA)/RA receptor (RAR) pathways is poorly understood. Here, we show that RA represses BMP signal duration by reducing the level of phosphorylated Smad1 (pSmad1). Through its nuclear receptor-mediated transcription, RA enhances the interaction between pSmad1 and its ubiquitin E3 ligases, thereby promoting pSmad1 ubiquitination and proteasomal degradation. This regulation depends on the RA-increased Gadd45 expression and MAPK activation. During the neural development in chicken embryo, the RA/RAR pathway also suppresses BMP signaling to antagonize BMP-regulated proliferation and differentiation of neural progenitor cells. Furthermore, this cross-talk between RA and BMP pathways is involved in the proper patterning of dorsal neural tube of chicken embryo. Our results reveal a mechanism by which RA suppresses BMP signaling through regulation of pSmad1 stability.

A multifunctional interlayer activated by lithiophilic electrospun Ag nanowires/polyvinylpyrrolidone nanofibers for efficient lithium storage.

A three-dimensional lithiophilic electrospun nanofiber framework with a Ag nanowires/polyvinylpyrrolidone (AgNWs/PVP) hybrid as a multifunctional interlayer has been designed to protect lithium metal anodes. The full cells with a LiFePO4 cathode and AgNWs/PVP interlayer have also realized excellent stable cyclability over 1000 cycles and high-rate capability.