Hydrogel morphogenesis induced by force-controlled growth.

Morphogenesis is one of the most marvelous natural phenomena. The morphological characteristics of biological organs develop through growth, which is often triggered by mechanical force. In this study, we propose a bioinspired strategy for hydrogel morphogenesis through force-controlled chemical reaction and growth under isothermal conditions. We adopted a double network (DN) hydrogel with sacrificial bonds. Applying mechanical force to the gel caused deformation and sacrificial bond rupture. By supplying monomers to the gel, the radicals generated by the bond rupture triggered the formation of a new network inside the deformed gel. This new network conferred plasticity to the elastic gel, allowing it to maintain its deformed shape, along with increased volume and strength. We demonstrated that sheet-shaped DN hydrogels rapidly adopted various three-dimensional shapes at ambient temperature when subjected to forces such as drawing and blowing. This mechanism enables morphogenesis of elastic hydrogels and will promote the application of these materials in biomedical fields and soft machines.

Effect of the Activation Force of Mechanophore on Its Activation Selectivity and Efficiency in Polymer Networks.

In recent decades, more than 100 different mechanophores with a broad range of activation forces have been developed. For various applications of mechanophores in polymer materials, it is crucial to selectively activate the mechanophores with high efficiency, avoiding nonspecific bond scission of the material. In this study, we embedded cyclobutane-based mechanophore cross-linkers (I and II) with varied activation forces (fa) in the first network of the double network hydrogels and quantitively investigated the activation selectivity and efficiency of these mechanophores. Our findings revealed that cross-linker I, with a lower activation force relative to the bonds in the polymer main chain (fa-I/fa-chain = 0.8 nN/3.4 nN), achieved efficient activation with 100% selectivity. Conversely, an increase of the activation force of mechanophore II (fa-II/fa-chain = 2.5 nN/3.4 nN) led to a significant decrease of its activation efficiency, accompanied by a substantial number of nonspecific bond scission events. Furthermore, with the coexistence of two cross-linkers, significantly different activation forces resulted in the almost complete suppression of the higher-force one (i.e., I and III, fa-I/fa-III = 0.8 nN/3.4 nN), while similar activation forces led to simultaneous activations with moderate efficiencies (i.e., I and IV, fa-I/fa-IV = 0.8 nN/1.6 nN). These findings provide insights into the prevention of nonspecific bond rupture during mechanophore activation and enhance our understanding of the damage mechanism within polymer networks when using mechanophores as detectors. Besides, it establishes a principle for combining different mechanophores to design multiple mechanoresponsive functional materials.

Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials.

OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

Azo-Crosslinked Double-Network Hydrogels Enabling Highly Efficient Mechanoradical Generation.

Double-network (DN) hydrogels have recently been demonstrated to generate numerous radicals by the homolytic bond scission of the brittle first network under the influence of an external force. The mechanoradicals thus generated can be utilized to trigger polymerization inside the gels, resulting in significant mechanical and functional improvements to the material. Although the concentration of mechanoradicals in DN gels is much higher than that in single-network hydrogels, a further increase in the mechanoradical concentration in DN gels will widen their application. In the present work, we incorporate an azoalkane crosslinker into the first network of DN gels. Compared with the traditional crosslinker N,N'-methylenebis(acrylamide), the azoalkane crosslinker causes a decrease in the yield stress but significantly increases the mechanoradical concentration of DN gels after stretching. In the azoalkane-crosslinked DN gels, the concentration of mechanoradicals can reach a maximum of ∼220 µM, which is 5 times that of the traditional crosslinker. In addition, DN gels with the azoalkane crosslinker show a much higher energy efficiency for mechanoradical generation. Interestingly, DN gels crosslinked by a mixture of azoalkane crosslinker and traditional crosslinker also exhibit excellent radical generation performance. The increase in the mechanoradical concentration accelerates polymerization and can broaden the application range of force-responsive DN gels to biomedical devices and soft robots.

Myelin sheath structure and regeneration in peripheral nerve injury repair.

Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence staining, and transcriptome analyses were used to investigate the structure and regeneration of the myelin sheath after end-to-end anastomosis, autologous nerve transplantation, and nerve tube transplantation in a rat model of sciatic nerve injury, with normal optic nerve, oculomotor nerve, sciatic nerve, and Schwann cells used as controls. The results suggested that the double-bilayer was the structural unit that constituted the myelin sheath. The major feature during regeneration was the compaction of the myelin sheath, wherein the distance between the 2 layers of cell membrane in the double-bilayer became shorter and the adjacent double-bilayers tightly closed together and formed the major dense line. The expression level of myelin basic protein was positively correlated with the formation of the major dense line, and the compacted myelin sheath could not be formed without the anchoring of the lipophilin particles to the myelin sheath.

Stroke of antiplatelet and anticoagulant therapy in patients with coronary artery disease: a meta-analysis of randomized controlled trials.

BACKGROUND: We performed a meta-analysis sought to investigate the risk of stroke with antiplatelet and anticoagulant therapies among patients with coronary artery disease (CAD). METHODS: We searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials from January 1995 to March 2020. Studies were retrieved if they reported data of stroke for patients with CAD and were randomized to receive intensive versus conservative antithrombotic therapies, including antiplatelet and oral anticoagulant (OAC). Analyses were pooled by random-effects modeling. A total of 42 studies with 301,547subjects were enrolled in this analysis. RESULTS: Intensive antithrombotic therapy significantly reduced risk of all stroke (RR 0.86, 95% CI 0.80-0.94) and ischemic stroke (RR 0.80, 95% CI 0.71-0.91), but increased risk of hemorrhagic stroke (RR 1.36, 95% CI 1.00-1.86) and intracranial hemorrhage (RR 1.46, 95% CI 1.17-1.81). Subgroup analyses indicated that OAC yields more benefit to all stroke than antiplatelet therapy (OAC: RR 0.73, 95% CI 0.58-0.92; Antiplatelet: RR 0.90, 95% CI 0.83-0.97; Between-group heterogeneity P value = 0.030). The benefit of antiplatelet therapy on all stroke and ischemic stroke were mainly driven by the studies comparing longer versus shorter duration of dual antiplatelet therapy (All stroke: RR 0.86, 95% CI 0.78-0.95; ischemic stroke: RR 0.84, 95% CI 0.75-0.94). CONCLUSIONS: Among CAD patients who have already received antiplatelet therapy, either strengthening antiplatelet or anticoagulant treatments significantly reduced all stroke, mainly due to the reduction of ischemic stroke, although it increased the risk of hemorrhagic stroke and intracranial hemorrhage. OAC yields more benefit to all stroke than antiplatelet therapy.

High-level production of d-pantothenic acid from glucose by fed-batch cultivation of Escherichia coli.

d-Pantothenic acid (D-PA) is an essential vitamin widely used in food, feed, chemical, and pharmaceutical industries. An Escherichia coli platform was developed for the high-level production of D-PA from glucose through fed-batch cultivation. Initially, the effects of different glucose feeding strategies D-PA synthesis were studied. It was found that D-PA production in glucose control (5 g/L) fed-batch culture reached 24.3 g/L, which was 4.09 times that in the batch culture. Next, the effect of auxotrophic amino acid (isoleucine)-limited feeding on D-PA production was investigated. The results revealed that isoleucine feeding decreased the accumulation of by-product acetic acid and promoted D-PA production significantly. Furthermore, an isoleucine feeding embedded multistage glucose supply strategy was established, and a maximum titer of 39.1 g/L was achieved. To the best of our knowledge, this levels are the highest reported so far in engineered E. coli for the D-PA production. The developed fed-batch feeding strategy may be useful for the industrial D-PA production by E. coli.

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography.

BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited. METHODS: In this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up. RESULTS: LDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8-29.2] µm vs 13.2 [7.4-18.6] µm; P = 0.029), greater increases in minimum lumen area (0.20[0.10-0.33] mm2 vs 0.13 [0.12-0.24] mm2; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8-24.5] vs. 8.4̊ [2.0-10.5]; P = 0.008). CONCLUSIONS: The addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04851769 . Registered 2 Mar 2019.

Novel 1H-pyrazolo[3,4-d]pyrimidin-6-amino derivatives as potent selective Janus kinase 3 (JAK3) inhibitors. Evaluation of their improved effect for the treatment of rheumatoid arthritis.

Selective JAK3 inhibitors have been shown to have a potential benefit in the treatment of autoimmune disorders. Here we report the identification of a series of pyrazolopyrimidine derivatives as potent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Most of these compounds (13k, 13n and 13 t), displayed stronger anti-JAK3 kinase activity and selectivity than tofacitinib. Furthermore, the most active inhibitor 13t (IC50 = 0.1 nM), also exhibited favourable selectivity for JAK3 in a panel of 9 kinases which contain the same cysteine. In a series of cytokinestimulated cellular analysis, compound 13 t, could potently block the JAK3-STAT signaling pathway. Further biological studies, including cellular antiproliferative activity assays and a rat adjuvant-induced arthritis model for in vivo evaluation, also indicated its efficacy and low toxicity in the treatment of rheumatoid arthritis. The results of these experimental explorations suggested that 13t is a promising lead compound for the development of selective JAK3 inhibitor with therapeutic potential in rheumatoid arthritis.

Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors.

Janus kinases (JAKs) play a key role in the proliferation, apoptosis and differentiation of immune cells, and JAKs are considered as an attractive target for the treatment of inflammatory and autoimmune diseases. Here we show the design and optimization of pyrimidine-4,6-diamine derivatives as selectivity JAK3 inhibitors. Compound 11e, which might interact with unique cysteine (Cys909) residue in JAK3, exhibited excellent JAK3 inhibitory activity (IC50 = 2.1 nM) and high JAK kinase selectivity. In cellular assay, 11e showed moderate potency inhibiting IL-2-stimulated T cell proliferation. The data supports the further development of novel JAKs inhibitors.

Structure-based design and synthesis of 1H-pyrazolo[3,4-d]pyrimidin-4-amino derivatives as Janus kinase 3 inhibitors.

Janus kinases (JAKs) regulate various inflammatory and immune responses and are targets for the treatment of inflammatory and immune diseases. Here we report the discovery and optimization of 1H-pyrazolo[3,4-d]pyrimidin-4-amino as covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Our optimization study gave compound 12a, which exhibited potent JAK3 inhibitory activity (IC50 of 6.2 nM) as well as excellent JAK kinase selectivity (>60-fold). In cellular assay, 12a exhibited potent immunomodulating effect on IL-2-stimulated T cell proliferation (IC50 of 9.4 µM). Further, compound 12a showed efficacy in delayed hypersensitivity assay. The data supports the further investigation of these compounds as novel JAKs inhibitors.

Characterization and expression analyses of somatolactin-α and -ß genes in rare minnows (Gobiocypris rarus) following waterborne cadmium exposure.

Using reverse transcription-polymerase chain reaction (RT-PCR) and RACE (rapid amplification of cDNA ends), somatolactin-α (rmSLα) and -ß (rmSLß) were identified from the pituitary gland of rare minnows (Gobiocypris rarus). The full-length cDNAs of these two genes were 1288 and 801 bp, encoding prepeptides of 250 and 228 amino acids residues, respectively. rmSLß can be detected in the brain (including the pituitary), ovary, testis, and gill, while rmSLα was mainly expressed in the brain. On the other hand, rmSLα was expressed in all the fetal developmental stages; however, rmSLß can just be detected in the stages since from 14 h post-fertilization (hpf). After exposure to acute waterborne cadmium (Cd), rmSLα was distinctly upregulated in juvenile rare minnows at all detected time points, from 24 to 96 h and 10 days, while rmSLß was significantly altered only in 96 h or 10-day treatment groups. As for adults, acute Cd exposure caused alterations of both rmSLα and rmSLß in the brain (containing the pituitary) at the 24 h; subchronic waterborne Cd treatment led to upregulation of rmSLα, while decrease of mSLß in the brain. Alteration of rmSL transcripts following waterborne Cd exposure further confirmed the endocrine disruption of this heavy metal. Besides, exposure to as low as 5 µg/L Cd caused alteration of rmSLα, which suggested that rmSLα might be a potential biomarker for risk assessment of aquatic Cd.

Periprocedural heparin bridging in patients receiving oral anticoagulation: a systematic review and meta-analysis.

BACKGROUND: Periprocedural heparin bridging therapy aims to reduce the risk of thromboembolic events in patients requiring an interruption in their anticoagulation therapy for the purpose of an elective procedure. The efficacy and safety of heparin bridging therapy has not been well established. OBJECTIVES: To compare through meta-analysis the effects of heparin bridging therapy on the risk of major bleeding and thromboembolic events of clinical significance among patients taking oral anticoagulants. METHODS: We searched PubMed, EMBASE and the Cochrane library from January 2005 to July 2016. Studies were included if they reported clinical outcomes of patients receiving heparin bridging therapy during interruption of oral anticoagulant for operations. Data were pooled using random-effects modeling. RESULTS: A total of 25 studies, including 6 randomized controlled trials and 19 observational studies, were finally included in this analysis. Among all the 35,944 patients, 10,313 patients were assigned as heparin bridging group, and the other 25,631 patients were non-heparin bridging group. Overall, compared with patients without bridging therapy, heparin bridging therapy increased the risk of major bleeding (OR = 3.23, 95%CI: 2.06-5.05), minor bleeding (OR = 1.52, 95%CI: 1.06-2.18) and overall bleeding (OR = 2.83, 95%CI: 1.86-4.30).While there was no significant difference in thromboembolic events (OR = 0.99,95%CI: 0.49-2.00), stroke or transient ischemic attack(OR = 1.45, 95%CI: 0.93-2.26,) or all-cause mortality (OR = 0.71, 95%CI: 0.31-1.65). CONCLUSIONS: Heparin-bridging therapy increased the risk of major and minor bleeding without decreasing the risk of thromboembolic events and all cause death compared to non-heparin bridging.

Site-Specific Pre-Swelling-Directed Morphing Structures of Patterned Hydrogels.

Morphing materials have promising applications in various fields, yet how to program the self-shaping process for specific configurations remains a challenge. Herein we show a versatile approach to control the buckling of individual domains and thus the outcome configurations of planar-patterned hydrogels. By photolithography, high-swelling disc gels were positioned in a non-swelling gel sheet; the swelling mismatch resulted in out-of-plain buckling of the disc gels. To locally control the buckling direction, masks with holes were used to guide site-specific swelling of the high-swelling gel under the holes, which built a transient through-thickness gradient and thus directed the buckling during the subsequent unmasked swelling process. Therefore, various configurations of an identical patterned hydrogel can be programmed by the pre-swelling step with different masks to encode the buckling directions of separate domains.

Light Responsive Microstructured Surfaces of Liquid Crystalline Network with Shape Memory and Tunable Wetting Behaviors.

Using adaptive soft materials to fabricate microstructured surfaces renders them with tunable topographic feature and thus controllable physical properties. Here, light responsive microstructured surfaces are reported with shape memory and tunable wetting behaviors; the surfaces are covered with micropillar arrays and constructed by lightly crosslinked azo-containing liquid crystalline network (LCN). UV light irradiation induces 25% contraction in length of the micropillars along their long axes and, as a consequence, the variations of topographic feature and wetting behavior of the surfaces. In addition, the LCNs exhibit shape memory properties, which can freeze the temporary topographic feature of microstructured surfaces (formed under UV irradiation and relatively high temperature) and enable application of their functionalities at mild conditions. This light responsiveness makes it feasible to remotely and precisely tune the local regions of microstructured surfaces, which should broaden the applications of adaptive surfaces in regulating the wetting, optical, and adhesion properties in selected regions.

Molecular characterization of Beclin 1 in rare minnow (Gobiocypris rarus) and its expression after waterborne cadmium exposure.

Beclin 1 plays an important role in autophagy and apoptosis which are well documented in mammals. However, relevant reports are rare in fish. This study characterized Beclin 1 of the rare minnow Gobiocypris rarus (rmBeclin 1), which encodes a peptide of 447 amino acids using RT-PCR and RACE. The deduced peptide showed 96.4 and 80.8% similarity to Beclin 1 of common carp and human, respectively. Semiquantitative RT-PCR revealed that rmBeclin 1 was ubiquitously expressed in all tested tissues of male and female fish in all developmental stages, even unfertilized eggs. RT-qPCR revealed that rmBeclin 1 mRNA transcripts were significantly up-regulated in gills after a 12 h treatment with waterborne CdCl2 but were decreased thereafter. However, rmBeclin 1 expression was decreased in the brain, but it was not significantly changed in other tissues. Subchronic CdCl2 exposure significantly increased rmBeclin 1 in the brain, but it distinctly decreased rmBeclin 1 in the gill and hepatopancreas. A dose-dependent effect was not observed in mature fish treated for 96 h, but a dose-dependent effect existed in immature fish treated for 10 days. Longer treatment (10 day) caused a significantly higher expression of rmBeclin 1 in the larvae groups. These data suggest that alterations in rmBeclin 1 after CdCl2 exposure are tissue-specific and time-related and that the dose-dependent effect was restricted to a certain concentration range and exposure time.

[Renal artery injury caused by Kawasaki disease].

OBJECTIVE: To investigate renal artery injury caused by Kawasaki disease (KD). METHODS: Forty-three children with KD were enrolled in the study. According to the blood pressure in the acute stage, these children were classified into normal blood pressure subgroup and increased blood pressure subgroup. Eighteen children with fever caused by acute upper respiratory tract infection were enrolled as the control group. The diameter of the origin of the main renal artery, hemodynamic parameters of the main renal artery and the renal interlobar artery, rennin activity, and levels of angiotensin II and aldosterone were compared between groups. RESULTS: During the acute stage of KD, both subgroups had a significantly smaller diameter of the origin of the main renal artery, a significantly higher resistance index (RI) of the main renal artery, and a significantly lower end-diastolic velocity (EDV) than the control group (P<0.05).The increased blood pressure subgroup had a significantly lower EDV of the interlobar artery than the normal blood pressure subgroup, a significantly higher RI than the normal blood pressure subgroup and the control group, as well as a significantly higher rennin activity and significantly higher levels of angiotensin II and aldosterone than the normal blood pressure subgroup (P<0.05). A significantly increased EDV and a significantly reduced RI of the renal interlobar artery were observed in the increased blood pressure subgroup in the subacute stage compared with the acute stage (P<0.05). CONCLUSIONS: KD may cause renal artery injury and early hemodynamic changes, resulting in a transient increase in blood pressure in some patients.

[Expression of CysLTR-1 and CysLTR-2 in adenoid tissues from children with adenoid hypertrophy].

OBJECTIVE: To examine the expression of cysteinyl leukotriene receptor-1 (CysLTR-1) and cysteinyl leukotriene receptor-2 (CysLTR-2) in the adenoid tissues from children with adenoid hypertrophy (AH) and to explore the role of leukotrienes in the pathogenesis of AH. METHODS: Sixty children with AH who were treated by adenoidectomy and/or tonsillectomy were classified into two groups: simple AH and AH plus allergic rhinitis (n=30 each). Twenty children who underwent tonsillectomy due to recurrent purulent tonsillitis were selected as the control group. The expression of CysLTR-1 and CysLTR-2 in the excised tonsil and/or adenoid tissues was determined by immunofluorescence histochemical labeling and integrated optical density measurement. RESULTS: The expression of CysLTR-1 and CysLTR-2 in the adenoid and tonsil tissues increased significantly in both the simple AH group and AH plus allergic rhinitis group compared with the control group (P<0.01). The expression of CysLTR-1 and CysLTR-2 in the AH plus allergic rhinitis group increased more significantly compared with the simple AH group (P<0.01). CONCLUSIONS: CysLTR-1 and CysLTR-2 are highly expressed in the adenoid tissues from children with AH, suggesting that leukotrienes are involved in the pathogenesis of AH.

Azobenzene as a photoswitchable mechanophore.

Azobenzene has been widely explored as a photoresponsive element in materials science. Although some studies have investigated the force-induced isomerization of azobenzene, the effect of force on the rupture of azobenzene has not been explored. Here we show that the light-induced structural change of azobenzene can also alter its rupture forces, making it an ideal light-responsive mechanophore. Using single-molecule force spectroscopy and ultrasonication, we found that cis and trans para-azobenzene isomers possess contrasting mechanical properties. Dynamic force spectroscopy experiments and quantum-chemical calculations in which azobenzene regioisomers were pulled from different directions revealed that the distinct rupture forces of the two isomers are due to the pulling direction rather than the energetic difference between the two isomers. These mechanical features of azobenzene can be used to rationally control the macroscopic fracture behaviours of polymer networks by photoillumination. The use of light-induced conformational changes to alter the mechanical response of mechanophores provides an attractive way to engineer polymer networks of light-regulatable mechanical properties.

Drug-eluting stents versus bare-metal stents in patients with decreased GFR: a meta-analysis.

BACKGROUND: Decreased estimated glomerular filtration rate (eGFR) is a strong predictor of both mortality and subsequent cardiac events after percutaneous coronary intervention. The safety and efficacy of drug-eluting (DESs) versus bare-metal stents (BMSs) in this population have not been evaluated adequately. STUDY DESIGN: A systematic review and meta-analysis. SETTING & POPULATION: Studies involving the comparison of clinical outcomes between DESs and BMSs in patients with eGFR <60 mL/min/1.73 m(2). Studies exclusively involving patients with ST-segment elevation myocardial infarction were excluded. SELECTION CRITERIA FOR STUDIES: MEDLINE (on Ovid), EMBASE, and the Cochrane Library databases from 2002-2013 were searched for studies comparing DESs with BMSs in patients with eGFR <60 mL/min/1.73 m(2). INTERVENTION: DES versus BMS implantation. OUTCOMES: Mortality, repeat revascularization, myocardial infarction, and stent thrombosis. RESULTS: Data from 26 comparative studies with 66,840 patients were included. Compared with BMSs, DESs were associated with significant reductions in repeat revascularization (OR, 0.61; 95% CI, 0.50-0.74; P < 0.001) and myocardial infarction (OR, 0.85; 95% CI, 0.79-0.92; P < 0.001), with no detectable difference in stent thrombosis (OR, 0.72; 95% CI, 0.46-1.12; P = 0.1). The superiority of DESs over BMSs in decreasing mortality also was documented (OR, 0.77; 95% CI, 0.65-0.90; P = 0.01). This survival benefit of DESs over BMSs was attenuated in randomized controlled trials or adjusted observational studies versus unadjusted observational studies. LIMITATIONS: Most studies were observational studies. Meta-analysis was not performed on individual patient data. CONCLUSIONS: DES use in patients with eGFR <60 mL/min/1.73 m(2) is associated with a reduced rate of repeat revascularization and myocardial infarction without increased risk of stent thrombosis. The true effect of DESs versus BMSs on mortality needs to be confirmed by randomized controlled trials.