Three New Compounds from Delphinium kamaonense Hunth and Their in†Vitro Cytotoxic and Potential Antioxidant Activities.

A new amide (1), two new phenylpropanoid derivatives (2, 3), along with three new natural products, including three nitrogen chirality compounds, N-(3-methoxy-1,3-dioxopropyl)-D-phenylalanine methyl ester (4), N-(3-methoxy-1,3-dioxopropyl)-L-phenylalanine methyl ester (5), and N-acetyl-L-phenylalanine methyl ester (6), as well as dimethyl (2R,3R)-2-hydroxy-3-(((E)-3-(4-hydroxyphenyl)acryloyl)oxy)succinate (7) and dimethyl (S,E)-2-((3-(4-hydroxy-3-methoxyphenyl)acryloyl)oxy)succinate (8) were isolated from Delphinium kamaonense Hunth. Their structures were elucidated by extensive analysis of 1D and 2D NMR, and HR-ESI-MS experiments, and the absolute configurations were determined by comparative analysis of specific optical rotation. Compound 1 exhibited a moderate cytotoxicity effect against Hep-3B cancer cell lines (IC50 41.39±0.13 µM) and an excellent antioxidant activity (IC50 0.527±0.06 µM in ABTS assay, and 1.235±0.09 µM in DPPH assay, respectively), which was superior to vitamin C in ABTS (IC50 1.670±0.07 µM) and DPPH (IC50 19.10±0.40 µM) methods.

Inhibitory effects of biochanin A on titanium particle-induced osteoclast activation and inflammatory bone resorption via NF-κB and MAPK pathways.

Revision operations have become a new issue after successful artificial joint replacements, and periprosthetic osteolysis leading to prosthetic loosening is the main cause of why the overactivation of osteoclasts (OCs) plays an important role. The effect of biochanin A (BCA) has been examined in osteoporosis, but no study on the role of BCA in prosthetic loosening osteolysis has been conducted yet. In this study, we utilised enzyme-linked immunosorbent assay, computed tomography imaging, and histological analysis. Results showed that BCA downregulated the secretion levels of tumor necrosis factor-α, interleukin-1α (IL-1α), and IL-1ß to suppress inflammatory responses. The secretion levels of receptor-activated nuclear factor-κB ligand, CTX-1, and osteoclast-associated receptor as well as Ti-induced osteolysis were also reduced. BCA effectively inhibited osteoclastogenesis and suppressed hydroxyapatite resorption by downregulating OC-related genes in vitro. Analysis of mechanisms indicated that BCA inhibited the signalling pathways of mitogen-activated protein kinase (P38, extracellular signal-regulated kinase, and c-JUN N-terminal kinase) and nuclear factor-κB (inhibitor κB-α and P65), thereby downregulating the expression of nuclear factor of activated T cell 1 and c-Fos. In conclusion, BCA may be an alternative choice for the prevention of prosthetic loosening caused by OCs.

Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-κB and MAPK pathways.

Prosthesis loosening is a highly troublesome clinical problem following total joint arthroplasty. Wear-particle-induced osteoclastogenesis has been shown to be the primary cause of periprosthetic osteolysis that eventually leads to aseptic prosthesis loosening. Therefore, inhibiting osteoclastogenesis is a promising strategy to control periprosthetic osteolysis. The possible mechanism of action of rhoifolin on osteoclastogenesis and titanium particle-induced calvarial osteolysis was examined in this study. The in vitro study showed that rhoifolin could strongly suppress the receptor activators of nuclear factor-κB (NF-κB) ligand-stimulated osteoclastogenesis, hydroxyapatite resorption, F-actin formation, and the gene expression of osteoclast-related genes. Western blot analysis illustrated that rhoifolin could attenuate the NF-κB and mitogen-activated protein kinase pathways, and the expression of transcriptional factors nuclear factor of activated T cells 1 (NFATc1) and c-Fos. Further studies indicated that rhoifolin inhibited p65 translocation to the nucleus and the activity of NFATc1 and NF-κB rhoifolin could decrease the number of tartrate-resistant acid phosphate-positive osteoclasts and titanium particle-induced C57 mouse calvarial bone loss in vivo. In conclusion, our results suggest that rhoifolin can ameliorate the osteoclasts-stimulated osteolysis, and may be a potential agent for the treatment of prosthesis loosening.

Network pharmacology-based prediction of the active ingredients, potential targets, and signaling pathways in compound Lian-Ge granules for treatment of diabetes.

AIMS: Compound Lian-Ge granules (CLGGs) is a traditional Chinese medicine preparation with good hypoglycemic effect and health function. This study was to predict its active ingredients, potential targets, signaling pathways, and investigate its mechanism of "ingredient-targets-pathways." METHODS: Pharmacodynamics studies on diabetic rats showed that CLGGs had an obvious hypoglycemic effect. On this basis, 27 hypoglycemic active ingredients were screened out. Their targets were confirmed by comparing with these hypoglycemic targets in PharmMapper and DrugBank databases via reversed pharmacophore matching approach. The relationships between ingredients and targets were revealed by comparing data in the String database. A network of "ingredient-target-passageway" was constructed. RESULTS: Studies showed that CLGGs had 24 active ingredients, ie, berberine, puerarin, danshinolic acid A, and sinigrin, etc. These ingredients involved nine targets, ie, insulin-like growth factor 1 receptor, insulin-degrading enzyme, ɑ-amylase, and so on, and 111 metabolic pathways, eg, hypoxia-inducible factor 1 signaling pathway, PI3K-Akt signaling pathway, mammalian target of rapamycin signaling pathway, and FoxO signaling pathway. CONCLUSION: Using network pharmacology methods, this study predicted the hypoglycemic active ingredients in CLGGs and revealed their targets, and provided a clue for further exploration of the hypoglycemic mechanism of CLGGs.

Undescribed compounds from Clinopodium chinense (Benth.) O. Kuntze and their coagulation activity studies.

Four rare compounds (1-4), including one 1,4-epoxy-benzoxepane derivative and one ringed prenylated naphthoquinoid skeleton, as well as one isopimarane-type diterpenoid and one megastigmane-type glycoside, along with three known megastigmane-type glycosides (5-7) were isolated from the ethanol extracts of C. chinense. Their structures were determined on the basis of 1D, 2D NMR, HR-ESI-MS and DP4+ analysis. Meanwhile, the in vitro evaluation indicated that compound 2 and 6 exhibited excellent procoagulant activities, which can significantly shorten prothrombin time (PT) and activated partial thromboplastin time (APTT), respectively.

Syntheses, crystal structures and intermolecular interactions of six novel pyrimidin-2-yl-substituted triaryltriazoles.

Six new pyrimidin-2-yl-substituted triaryltriazoles, namely, 4-(4-R-phenyl)-3-(pyridin-2-yl)-5-(pyrimidin-2-yl)-1,2,4-triazoles [L1: R = methoxy (OCH3); L2: R = methyl (CH3); L3: R = nil (H); L4: R = bromo (Br); L5: R = chloro (Cl); L6: R = fluoro (F)] have been successfully synthesized with yields in the range 68.3-81.7%. Compounds L1-6 have been characterized by UV-Vis, FT-IR, 1H NMR and ESI-MS spectroscopy, and elemental analysis. In addition, the structures of L2-6 and the ethanol monosolvate of L2 (L2·C2H5OH) have been determined by single-crystal X-ray diffraction. A combination of intermolecular O-H...N, C-H...O, C-H...N and C-H...π hydrogen bonds connects the components of L2·C2H5OH into a three-dimensional (3D) framework. A combination of three intermolecular C-H...N hydrogen bonds links the molecules of L2 or L3 into two different 3D networks. Both L4 and L5 show a similar 3D net structure through two intermolecular C-H...N hydrogen bonds and one kind of C-H...π interaction. However, L6 displays a more complicated 3D net structure via three intermolecular C-H...N hydrogen bonds and one kind of C-H...π interaction. Notably, an interaction between the π-electrons and the lone-pair p-electrons of a halogen atom (Br, Cl and F) is observed in L4-6, which will further stabilize the 3D networks. The intermolecular interactions in L2·C2H5OH and L2-6 were further investigated by 3D Hirshfeld surface analyses and 2D fingerprint plots to show that the prominent interactions are H...H, N...H/H...N and C...H/H...C contacts.

Effect of transcutaneous electrical acupoint stimulation based on the theory of "qi ascending and descending movement" on autonomic nervous system and gastrointestinal function in patients after general anesthesia laparoscopic cholecystectomy. / 基于"气机升降"ç†è®ºç»çš®ç©´ä½ç”µåˆºæ¿€å¯¹å ¨éº»è ¹è ”é•œèƒ†å›Šåˆ‡é™¤æœ¯åŽæ‚£è€ è‡ªä¸»ç¥žç»å’Œèƒƒè‚ åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) based on the theory of "qi ascending and descending movement" in patients after general anesthesia laparoscopic cholecystectomy, so as to explore the impact of TEAS on the autonomic nervous system and gastrointestinal function of patients. METHODS: A total of 204 patients scheduled to undergo general anesthesia laparoscopic cholecystectomy were selected and randomly divided into control, double acupoints and multiple acupoints groups, with 68 cases in each group. For patients in the multiple acupoints group, TEAS was applied at Zusanli (ST36), Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12), Taichong (LR3), and Neiguan (PC6) 30 min before anesthesia induction until the end of the surgery. In the double acupoints group, TEAS was applied only at ST36 and PC6. No electrical stimulation was applied in the control group. The postoperative bloating, bowel sound recovery time, first farting time, first defecation time, length of hospital stay, nausea and vomiting were compared among the three groups. Heart rate variability was monitored by twelve-lead electrocardiogram to evaluate the autonomic nervous function of the patients, including the low frequency power/high frequency power ratio (LF/HF), the standard deviation of all sinus RR intervals (SDNN), and the root mean square of difference between successive normal RR intervals (RMSSD). RESULTS: At 6 h and 24 h after surgery, the symptoms of bloating, nausea and vomiting in the multiple acupoints group and double acupoints group were significantly improved compared to the control group (P<0.05), and the multiple acupoints group was superior to the double acupoints group (P<0.05). Compared with the control group, the bowel sound recovery time, first farting time, first defecation time, and length of hospital stay were significantly shorter (P<0.05) in the multiple acupoints group and double acupoints group, and the multiple acupoints group was superior to the double acupoints group (P<0.05). At 1 d and 2 d after surgery, compared with the control group, LF/HF was decreased (P<0.05) while SDNN and RMSSD were increased (P<0.05) in the multiple acupoints group and double acupoints group, and there was a significant difference between the two groups (P<0.05). CONCLUSIONS: TEAS treatment based on the theory of "qi ascending and descending movement" can relieve gastrointestinal dysfunction, reduce early postoperative sympathetic nerve excitement and maintain parasympathetic nerve tension in patients after general anesthesia laparoscopic cholecystectomy, thereby promoting gastrointestinal function recovery.

[Long-term lung protection of probiotics in children with sepsis and its mechanism].

OBJECTIVE: To observe the effects of probiotics supplementation on the natural killer T cell (NKT cell) and inflammatory factors in children with sepsis and its protective effect on long-term lung function. METHODS: A total of 100 children with sepsis admitted to the department of pediatric intensive care unit (PICU) of Henan Provincial People's Hospital from March 2021 to May 2022 were selected as the research objects. The children were randomly divided into placebo group and probiotic group, 50 cases in each group. In addition to the conventional treatment, the probiotic group was given oral or nasal administration of 0.5 g probiotics, three times a day for 30 days, and the placebo group received oral placebo. 40 healthy children were selected as the healthy control group. The levels of interleukins (IL-4, IL-10), interferon-γ (IFN-γ) and immunoglobulin E (IgE), percentages of NKT cell in blood and induced sputum, lung function of the two groups of children with sepsis were measured before treatment, 7 days after treatment, and during follow-up. All these data were compared with those of healthy children. Kaplan-Meier analysis was used to compare the incidence of cough varied cough (CVA) between the two septic groups. Multiple linear regression analysis was used to explore the influence of various factors on the proportion of NKT cells in induced sputum. RESULTS: In the placebo group, 2 cases died and 4 cases were lost to follow-up. In the probiotics group, 3 cases died and 5 cases were lost to follow-up. All the inflammatory factors of two groups decreased slowly after 7 day after treatment. There was no significance in the parameters of the two groups, but the levels of probiotic group declined more evidently. During the follow-up, a further decrease of inflammatory factors in probiotic group could be found, the levels of IL-4 and IL-10 were significantly different from those in the placebo group [IL-4 (ng/L): 20.3±9.3 vs. 27.6±11.9, IL-10 (ng/L): 23.1±6.8 vs. 14.4±4.4, both P < 0.05], with a significant decrease in IgE level (µg/L: 53.0±15.6 vs. 64.2±16.9, P < 0.05]. The results of flow cytometry showed that the percentage of NKT cell in peripheral blood in two septic groups decreased gradually, and the proportion of peripheral blood NKT cells in the probiotics group was significantly lower than that in the placebo group after 7 days of treatment [(4.2±0.9)% vs. (5.3±1.2)%, P < 0.05]. In the follow-up, the level of NKT cell in peripheral blood and induced sputum in probiotic group were lower than the placebo group [peripheral blood: (0.024±0.009)% vs. (0.029±0.008)%, induced sputum: (0.025±0.008)% vs. (0.035±0.01)%, both P < 0.05], which were similar to those in the healthy control group. Meanwhile, the percentage of predicted peak expiratory (PEF%) and ratio of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of probiotic group were higher than those in the placebo group [PEF%: (91.3±4.8)% vs. (85.8±8.6)%, FEV1/FVC ratio: (91.8±4.7)% vs. (87.2±7.4)%, both P < 0.05]. Although there was no significance in the incidence of CVA between two septic groups according to the Kaplan-Meier curve analysis, multiple linear regression analysis showed mechanical ventilation and allergic history were the risk factors for the increase of NKT cells [ß values were 0.584, 0.601, 95% confidence interval (95%CI) were 0.069 to 1.099, 0.011 to 1.192, P = 0.027, 0.046], and probiotics was an independent protective factor for the relieve of increase in NKT cells (ß value was -0.984,95%CI was -1.378 to -0.591, P = 0.001). CONCLUSIONS: Application of probiotics to septic children early could promote the recovery of NKT cell and inflammatory factors, and alleviate the lung function injury induced by them during follow-up, which is helpful to improve the long-term prognosis of the patients.

Anti-inflammatory abietanes diterpenes and triterpenoids isolated from Clinopodium polycephalum.

Two previously undescribed diterpenes (1 and 2), as well as one curious triterpenoid were isolated from Clinopodium polycephalum, a medicinal plant distributed in southwestern and eastern China. Their structures were elucidated using MS analyses, UV spectrum, and extensive 2D-homo and heteronuclear NMR data interpretations. Among them, 1 had an unusual skeletal characteristic produced by a rare methyl migration pathway. All monomer compounds exhibited inhibitory effects on NO production in LPS-induced RAW 264.7 cells without affecting cell viabilities, which were comparable to that of positive control.

Upcycling of dynamic thiourea thermoset polymers by intrinsic chemical strengthening.

Thermoset polymers are indispensable but their environmental impact has been an ever-increasing concern given their typical intractability. Although concepts enabling their reprocessing have been demonstrated, their practical potential is limited by the deteriorated performance of the reprocessed materials. Here, we report a thiourea based thermoset elastomer that can be reprocessed with enhanced mechanical properties. We reveal that the thiourea bonds are dynamic which leads to the reprocessibility. More importantly, they can undergo selective oxidation during high temperature reprocessing, resulting in significant chemical strengthening within certain reprocessing cycles. This is opposite to most polymers for which reprocessing typically results in material deterioration. The possibility of having materials with inherent reprocessing induced performance enhancement points to a promising direction towards polymer recycling.

A novel multidimensional strategy to evaluate Belamcanda chinensis (L) DC and Iris tectorum Maxim based on plant metabolomics, digital reference standard analyzer and biological activities evaluation.

BACKGROUND: Belamcanda chinensis (L.) DC. (BC) belongs to the family of Iridaceae and is widely cultivated and used in many Chinese patent medicine and Chinese medicinal formulae. However, due to the high similarities in appearance such as color and shape to Iris tectorum Maxim (ITM), another plant from the same family, BC is often confused or even misused with ITM. METHODS: Therefore, in order to distinguish the chemical constituents, qualities and biological activities of BC and ITM, multiple technologies including plant metabolomics, digital reference standard (DRS) analyzer and biological activities assay were employed to provide a sufficient basis for their practical applications. RESULTS: In plant metabolomics, the PCA and OPLS-DA score plot indicated the obvious differences in chemical profiling between BC and ITM and 6 compounds were successfully identified to contribute to the differences. In DRS study, the fingerprints of 10 and 8 compounds in BC and ITM were developed based on DRS analyzer, respectively, involving relative retention time (RRT) method and linear calibration using two reference substances (LCTRS) technique. The DRS analyzer also accurately identified 10 and 8 compounds from BC and ITM, respectively, by using only two reference standards. In biological activities assay, BC had a better anticancer effect than ITM due to the high abundance of irigenin, while ITM showed stronger hepatoprotective activity than BC because of the high abundance of tectoridin. CONCLUSIONS: Therefore, due to the significant differences of B. chinensis and I. dichotoma in chemical composition and biological activities, the current studies strongly proved that these two medicinal plants could not be mixed in industrial production and clinical medication.

CYP3A4 inducer aggravates big flower Evodiae Fructus-induced hepatotoxicity whereas limonin attenuates its hepatotoxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Evodiae Fructus (EF), the traditional Chinese medicine, has been typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It is a mild toxicity herb-medicine listed in Sheng Nong's Herbal Classic. Recently, EF was reported to have toxicity or no toxicity in some investigations. Toxicity and approaches to reducing toxicity of EF are of great interest. Limonin (LIM), a major triterpenoid component of EF, also had various pharmacological activities such as anti-inflammatory, anticancer, and antioxidant effects. However, little attention was paid to the role of LIM in EF-induced hepatotoxicity. AIM OF STUDY: The study aimed to address the problem of controversial hepatotoxicity of EF, evaluate the role of CYP3A4 inducer/inhibitor in EF-induced hepatotoxicity and disclose the effect of LIM in EF-induced hepatotoxicity. MATERIALS AND METHODS: The chemical compositions and hepatotoxicity of small flower EF (SEF), medium flower EF (MEF), big flower EF (BEF) and the "organ knock-out" samples (the shell and seed part of BEF) were investigated. Simultaneously, C57BL-6 mice were randomly divided into four groups, which were given orally administered BEF, BEF in combination with dexamethasone (DEX), BEF in combination with ketoconazole (KTC), and BEF in combination with LIM, respectively. RESULTS: In this study, more alkaloids and less LIM were detected in BEF compared with the compounds in SEF and MEF. Furthermore, we found that BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in SEF and MEF groups. In addition, no LIM was detected in the shell part of BEF and five alkaloids were not detected in the seed part of BEF. Correspondingly, the shell part of BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in the seed part of BEF group. It was also found that the BEF-induced hepatotoxicity was remarkably exacerbated when the mice were pretreated with DEX whereas the BEF-induced hepatotoxicity could be reversed by pretreatment with KTC or LIM. CONCLUSIONS: Based on the results in this study, the misuse of BEF but not SEF and MEF could produce hepatotoxicity. The hepatotoxicity difference of different categories of EF might be associated with the relative contents of alkaloids and LIM. In addition, the results demonstrated that CYP3A4 inducer aggravated BEF-induced hepatotoxicity and LIM attenuated its hepatotoxicity.

Sequence-Rearranged Cocrystalline Polymer Network with Shape Reconfigurability and Tunable Switching Temperature.

Switching temperature (Tsw) is a key parameter governing the service condition of shape memory polymers (SMPs). However, tuning Tsw of SMPs often requires sophisticated synthesis or intricate processing. Herein, we report a simple yet effective strategy to prepare the SMPs with tunable Tsw and good reconfigurability by using the cocrystalline polyesters as the reversible phase. The cocrystallizable copolyesters with rearranged sequences were prepared by the transesterification of mixed polyester diols and then photo-cross-linked to achieve the SMP networks. Cocrystallization of copolymer blocks endows the SMP networks tunable melting point and relatively high crystallinity, affording the network good shape fixing and recovery ability at body temperature. Besides, the dynamic nature of transesterification, that enables the network to have good shape reconfigurability, allows for the easy processing of SMPs with complicated shapes. The reconfigurable SMPs capable of actuating at the body temperature show great potential for use as biomedical devices.

Light-triggered topological programmability in a dynamic covalent polymer network.

Dynamic covalent polymer networks exhibit unusual adaptability while maintaining the robustness of conventional covalent networks. Typically, their network topology is statistically nonchangeable, and their material properties are therefore nonprogrammable. By introducing topological heterogeneity, we demonstrate a concept of topology isomerizable network (TIN) that can be programmed into many topological states. Using a photo-latent catalyst that controls the isomerization reaction, spatiotemporal manipulation of the topology is realized. The overall result is that the network polymer can be programmed into numerous polymers with distinctive and spatially definable (thermo-) mechanical properties. Among many opportunities for practical applications, the unique attributes of TIN can be explored for use as shape-shifting structures, adaptive robotic arms, and fracture-resistant stretchable devices, showing a high degree of design versatility. The TIN concept enriches the design of polymers, with potential expansion into other materials with variations in dynamic covalent chemistries, isomerizable topologies, and programmable macroscopic properties.

Synergetic Chemical and Physical Programming for Reversible Shape Memory Effect in a Dynamic Covalent Network with Two Crystalline Phases.

A recently emerged reversible shape memory effect greatly extends the capability of shape memory polymers and their practical potential. Physical confinement and chemical fixation are individually known to be effective in introducing network anisotropy essential for reversible shape memory. Herein, we demonstrate that synergetic combination of these two mechanisms effectively diversifies the shape-shifting behavior. Specifically, we introduce a transesterification catalyst into a network containing two crystalline phases: poly(ε-caprolactone) (PCL) and poly(ω-pentadecalactone) (PPDL). The reversible shape memory behavior of the resulting system can be programmed via the physical confinement by the PPDL phase and the chemical plasticity by the dynamic ester exchange. We illustrate that the two programming mechanisms can operate in a noninterfering way that allows achieving a synergetic benefit, notably realizing a zero-set reversible shape memory behavior. Our study points to a direction in diversifying the behaviors of reversible shape memory polymers and expands the scope for potential engineering devices.

Emulsion Lyophilization as a Facile Pathway to Fabricate Stretchable Polymer Foams Enabling Multishape Memory Effect and Clip Application.

Solvent freezing is an important method to produce polymer foams with highly tunable pore structure. However, foams prepared from aqueous solution precursors commonly suffer from poor water resistance, whereas those organo-phase systems are not environmental friendly. Here, we present that using an emulsion lyophilization method can overcome such a contradiction and synthesize multifunctional polymer foams. Commercially available polyacrylate-based emulsions with various targeted glass transition temperatures (Tgs) were applied. Adipodihydrazide molecules contained in the water phase of the emulsions reacted with the acetyl groups on the polymers during the freeze-drying, forming elastic networks to maintain the pore structure. The foams can tolerate a 650% elongation without failure and are notch insensitive. The porosity of the foams can be tuned from approximately 45 to 90% via lyophilization of diluted emulsions. The facile blending of emulsions with different targeted Tgs enabled foams with multishape memory capability. Moreover, the foams showed an excellent mechanical damping property, and the slow recovery nature enabled a clip application of clamping extremely weak objects.

4D Printing of a Digital Shape Memory Polymer with Tunable High Performance.

Shape memory polymers (SMP) with 3D geometries and tunable shape-shifting behavior can open up new opportunities in intelligent devices. Achieving both simultaneously is difficult for conventional approaches. 4D printing allows fabrication of complex 3D SMP geometries that can change shapes (i.e., the fourth dimension is time), but tuning the shape memory response is challenging because of the printing constraints. Here, we report a material and process concept that allows digital light fabrication of SMP with fine control of not only the geometries but also the shape memory characteristics, within a printing time of 30 s. Digital light modulation allows spatio-temporal tuning of the material properties including shape memory transition temperature, rubbery modulus, and maximum elongation (up to 250%). Consequently, the process allows producing multiple-SMP within a single material construct using the same printing precursor. We demonstrate that this unique attribute is beneficial in constructing unusual shape-shifting 3D nano-photonic and electronic devices. The simplicity and versatility of our approach facilitates its future expansion into a wide range of geometrically complex devices with advanced functions.

Programming a crystalline shape memory polymer network with thermo- and photo-reversible bonds toward a single-component soft robot.

The need to support the two most basic functions [three-dimensional (3D)-shaped support and actuation] independently for a typical robot demands that at least two components should be used in its construction. Therefore, component assembly is unavoidable despite the ultimate dream of creating assembly-free robots. We devise a strategy that uses a programmable crystalline shape memory polymer with thermo- and photo-reversible bonds to create a single-component robot. The global 3D-shaped structural support is fabricated via a plasticity-based origami technique enabled by the thermo-reversible bonds. More critically, precisely controlled localized actuation can be programmed into the 3D origami via spatially defined reversible shape memory using the photo-reversible bonds. The overall result is that a polymer thin film can be programmed into various soft robots including a 3D crane and an elephant. Besides reversible shape memory, other types of actuation mechanisms can be potentially introduced via a similar principle. Thus, our strategy represents a general method to create single-component soft robots.

Liraglutide protects ß-cell function by reversing histone modification of Pdx-1 proximal promoter in catch-up growth male rats.

AIMS: Catch-up growth after a period of nutritional deprivation in adulthood is related to the onset of metabolic disorders. This process involves chromatin remodelling of the Pdx-1 gene in pancreas. The objective of this study was to determine the chromatin remodelling mechanism of GLP-1 analogue Liraglutide upon Pdx-1 in catch-up growth rats in vivo and in vitro. METHODS: Five-week-old male specific pathogen free (SPF) Wistar rats were randomly divided into normal group, catch-up growth group and Liraglutide group. Hyperglycemic clamp test and glucose-stimulated insulin secretion test were carried out to evaluate ß-cell function in vivo and in vitro. The histone H3 modification changes at the Pdx-1 proximal promoter were assessed by chromatin immunoprecipitation. RESULTS: The catch-up growth state was characterized by less recruitment of histone H3 lysine4 trimethylation and histone H3 acetylation and more recruitment of histone H3 lysine9 dimethylation at the Pdx-1 proximal promoter. Liraglutide treatment reversed these epigenetic changes and increased Pdx-1 expression, which could be abrogated by GLP-1 receptor antagonist Exendin 9-39. The ß-cell function of catch-up growth rats was improved after Liraglutide treatment. CONCLUSIONS: The protective effects of Liraglutide on pancreatic islet ß-cell function may be related to histone H3 modification at the Pdx-1 proximal promoter during catch-up growth and could be used to treat catch-up growth-related metabolic disorders.