Patients admitted to the intensive care unit (ICU) after surgery often develop sleep disturbances. The authors tested the hypothesis that low-dose dexmedetomidine infusion could improve sleep ...architecture in nonmechanically ventilated elderly patients in the ICU after surgery.
This was a pilot, randomized controlled trial. Seventy-six patients age 65 yr or older who were admitted to the ICU after noncardiac surgery and did not require mechanical ventilation were randomized to receive dexmedetomidine (continuous infusion at a rate of 0.1 μg kg h; n = 38) or placebo (n = 38) for 15 h, i.e., from 5:00 PM on the day of surgery until 8:00 AM on the first day after surgery. Polysomnogram was monitored during the period of study-drug infusion. The primary endpoint was the percentage of stage 2 non-rapid eye movement (stage N2) sleep.
Complete polysomnogram recordings were obtained in 61 patients (30 in the placebo group and 31 in the dexmedetomidine group). Dexmedetomidine infusion increased the percentage of stage N2 sleep from median 15.8% (interquartile range, 1.3 to 62.8) with placebo to 43.5% (16.6 to 80.2) with dexmedetomidine (difference, 14.7%; 95% CI, 0.0 to 31.9; P = 0.048); it also prolonged the total sleep time, decreased the percentage of stage N1 sleep, increased the sleep efficiency, and improved the subjective sleep quality. Dexmedetomidine increased the incidence of hypotension without significant intervention.
In nonmechanically ventilated elderly patients who were admitted to the ICU after noncardiac surgery, the prophylactic low-dose dexmedetomidine infusion may improve overall sleep quality.
Polymers with a large π‐electron conjugated system have aroused extensive concern in photocatalysis due to their appropriate bandgap and high stability. In order to overcome such drawbacks as its ...inadequate visible light absorption and rapid recombination of the photogenerated electron‐hole pairs of graphic carbon nitride (g‐C3N4), a facile strategy is proposed to tune its electronic structure by grafting small molecules. The conjugated photocatalysts were prepared by attaching 3‐Aminobenzoic acid (AB) and 6‐Aminopyridine‐2‐carboxylic acid (APy) to the framework of g‐C3N4 via low‐temperature condensation. The obtained catalysts UCN‐AB and UCN‐APy possess higher visible light absorption that results from the modified band structure by extending π‐electron delocalization. Additionally, AB and APy worked as the electron acceptors which further enhance transport of the photogenerated electrons. The optimal UCN‐AB and UCN‐APy accomplished remarkable photocatalytic hydrogen evolution rates of 104.0 and 133.2 μmol/h, respectively, which are nearly four or five times of that over g‐C3N4. This work provides a simple and feasible modification approach to extend π‐electron delocalization in g‐C3N4 with a stronger visible light response and accelerated charge transfer for high photocatalytic hydrogen evolution.
Light is power: Solar‐to‐hydrogen conversion based on photocatalytic water splitting is promising to overcome serious energy crisis. Photocatalyst UCN‐APy was synthesized by attaching 6‐Aminopyridine‐2‐carboxylic acid (APy) to g‐C3N4 via low‐temperature amide condensation. The optimized catalyst exhibits significantly improved activity with H2 generation rate of 133.2 μmol/h because of the extensive π‐delocalization and electron‐withdrawing effect. This study provides a simple and feasible modification approach to design extensive π‐electron delocalized C3N4‐based photocatalysts with high performance.
Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An ...integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD. In-depth network analysis results of the top diseases, functions, pathways and upstream regulators implied that a common underlying mechanism linking DHI's role in stroke and CAD treatment was inflammatory response in the process of atherosclerosis. Experimentally, DHI exerted comprehensive anti-inflammatory effects on LPS, ox-LDL or cholesterol crystal-induced NF-κB, c-jun and p38 activation, as well as IL-1β, TNF-α, and IL-10 secretion in vascular endothelial cells. Ten of 14 predicted ingredients were verified to have significant anti-inflammatory activities on LPS-induced endothelial inflammation. DHI exerts pharmacological efficacies on both stroke and CAD through multi-ingredient, multi-target, multi-function and multi-pathway mode. Anti-endothelial inflammation therapy serves as a common underlying mechanism. This study provides a new understanding of DHI in clinical application on cardiovascular and cerebrovascular diseases.
Herein, the first example of visible‐light‐driven, cobalt‐catalyzed transfer semihydrogenation of alkynes to alkenes is reported. It is carried out by using IrdF(CF3)ppy2(dtbbpy)PF6 as ...photosensitizer, CoBr2/n‐Bu3P as proton‐reducing catalyst, and i‐Pr2NEt/AcOH as the hydrogen source. Under the established catalytic system, the semihydrogenation proceeds with Z as the major selectivity and with inhibition of over‐reduction. Under mild reaction conditions, both internal and terminal alkynes, as well as reducible functional groups such as halogen, cyano, and ester, are tolerated. Preliminary mechanistic studies revealed the dual role of the photosensitizer in initiating the reaction via a single‐electron transfer process and controlling the stereoselectivity via an energy transfer process.
A series of novel disulfides containing 1,3,4-thiadiazole moiety were designed, synthesized, and the structures of all products were identified by spectral data (IR, NMR, and high resolution ...(HR)-MS). Their in vitro antiproliferative activities were evaluated using 2-(2-methoxy-4-nitro-phenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfopheyl)-2H-tetrazolium monosodium salt (CCK-8) assay against human cancer cell lines, A549 (human lung cancer cell), HeLa (human cervical cancer cell), SMMC-7721 (human liver cancer cell) and normal cell lines L929. The bioassay results indicated that most of the tested compounds 6a–k, 7a–k and 8a–k exhibited antiproliferation with different degrees, and some compounds showed better effects than positive control 5-fluorouracil (5-FU) against various cancer cell lines. Among these compounds, compound 6e exhibited the most potent inhibitory activity against A549 cells with IC50 value of 3.62 µM. Compounds 6i, 7a, 7g, 8a and 8b showed significantly antiproliferative activities against HeLa cells with IC50 values of 3.88, 3.76, 3.59, 3.38 and 3.12 µM, respectively. Compounds 6a, 7a and 8a owned high antiproliferative activities against SMMC-7721 cells with IC50 values of 2.54, 2.69 and 2.31 µM, respectively. Furthermore, all of the tested compounds showed weak cytotoxic effect against the normal cell lines L929. Based on the preliminary results, the substituent groups are vital for improving the potency and selectivity of this class of compounds.
An operationally simple anhydrous carbene insertion reaction to construct DNA‐encoded libraries (DEL) is reported. The developed reaction employs visible light photolysis of diazo compounds and ...Reversible Adsorption to Solid Support (RASS) strategy. From readily available amines, alcohols, phenols, and carboxylic acids, a variety of high‐value molecules, including useful unnatural amino acids, ethers, and esters, promising clinical drug derivatives, and bioactive molecules have been constructed.
YAP is the major downstream effector of the Hippo pathway, which controls cell growth, tissue homeostasis, and organ size. Aberrant YAP activation, resulting from dysregulation of the Hippo pathway, ...is frequently observed in human cancers. YAP is a transcription co‐activator, and the key mechanism of YAP regulation is its nuclear and cytoplasmic translocation. The Hippo pathway component, LATS, inhibits YAP by phosphorylating YAP at Ser127, leading to 14‐3‐3 binding and cytoplasmic retention of YAP. Here, we report that osmotic stress stimulates transient YAP nuclear localization and increases YAP activity even when YAP Ser127 is phosphorylated. Osmotic stress acts via the NLK kinase to induce YAP Ser128 phosphorylation. Phosphorylation of YAP at Ser128 interferes with its ability to bind to 14‐3‐3, resulting in YAP nuclear accumulation and induction of downstream target gene expression. This osmotic stress‐induced YAP activation enhances cellular stress adaptation. Our findings reveal a critical role for NLK‐mediated Ser128 phosphorylation in YAP regulation and a crosstalk between osmotic stress and the Hippo pathway.
Synopsis
Yes‐associated protein (YAP) is the major transcriptional co‐activator of the Hippo pathway, and its activity is determined by its subcellular localization. This study shows that osmotic stress induces Ser128 phosphorylation of YAP by the nemo‐like kinase (NLK), which results in its nuclear accumulation and the induction of downstream targets.
Osmotic stress induces transient nuclear localization of YAP, despite LATS‐dependent Ser127 phosphorylation.
Osmotic stress activates NLK to phosphorylate YAP on Ser128, which interferes with 14‐3‐3 binding and increases its nuclear localization.
NLK‐dependent transient YAP activation may serve as an early response for cells to adapt to osmotic stress.
Yes‐associated protein (YAP) is the major transcriptional co‐activator of the Hippo pathway, and its activity is determined by its subcellular localization. This study shows that osmotic stress induces Ser128 phosphorylation of YAP by the nemo‐like kinase (NLK), which results in its nuclear accumulation and the induction of downstream targets.
Layered transition metal oxide cathodes have been one of the dominant cathodes for lithium‐ion batteries with efficient Li+ intercalation chemistry. However, limited by the weak layered interaction ...and unstable surface, mechanical and chemical failure plagues their electrochemical performance, especially for Ni‐rich cathodes. Here, adopting a simultaneous elemental‐structural atomic arrangement control based on the intrinsic Ni−Co−Mn system, the surface role is intensively investigated. Within the invariant oxygen sublattice of the crystal, a robust surface with the synergistic concentration gradient and layered‐spinel intertwined structure is constructed on the model single‐crystalline Ni‐rich cathode. With mechanical strain dissipation and chemical erosion suppression, the cathode exhibits an impressive capacity retention of 82 % even at the harsh 60 °C after 150 cycles at 1 C. This work highlights the coupling effect of structure and composition on the chemical‐mechanical properties, and the concept will spur more researches on the cathodes that share the same sublattice.
The critical effect of intrinsic surface composition and structure on the properties of single‐crystalline Ni‐rich layered oxides as cathode material for Li‐ion batteries is demonstrated via control of the elemental‐structural surface atomic arrangement. The concomitant concentration gradient and layered‐spinel intertwined structure were thus constructed, enabling the chemical‐mechanical robustness of Ni‐rich cathodes in the electrochemical process.
A series of hydrogel‐based inks are developed to print 3D structures capable of reversible shape deformation in response to hydration and temperature. The inks are made of large polymer chains and UV ...curable monomers which form interpenetrating polymer networks after polymerization. By taking advantage of the long polymer chains in the ink formulations, it is possible to adjust the rheological properties of the inks to enable 3D printing. Hydrogels produced from the inks exhibit robust mechanical performance with their mechanical properties controlled by the nature of the long polymer chains within their networks. In this paper, hydrogel hinges are made from various ink formulations and a simple model is developed to predict their bending characteristics, including the bending curvature and bending angle. This model can be used as a guide to determine optimal parameters for a wide range of materials combination to create all‐hydrogel structures that undergo desired shape transitions.
4D printed hybrid hydrogels capable of reversible shape transition in response to hydration and temperature are prepared. The shape deformation of printed hydrogel sheets is determined by the print design and the constituting hydrogels properties. The latter is controlled by the development of tailored inks.
The thromboxane A2 receptor (TP) has been implicated in restenosis after vascular injury, which induces vascular smooth muscle cell (VSMC) migration and proliferation. However, the mechanism for this ...process is largely unknown. In this study, we report that TP signaling induces VSMC migration and proliferation through activating YAP/TAZ, two major downstream effectors of the Hippo signaling pathway. The TP-specific agonists 1S-1α,2α(Z),3β(1E,3S*),4 α-7-3-3-hydroxy-4-(4-iodophenoxy)-1-butenyl-7-oxabicyclo2.2.1hept-2-yl-5-heptenoic acid (I-BOP) and 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619) induce YAP/TAZ activation in multiple cell lines, including VSMCs. YAP/TAZ activation induced by I-BOP is blocked by knockout of the receptor TP or knockdown of the downstream G proteins Gα12/13. Moreover, Rho inhibition or actin cytoskeleton disruption prevents I-BOP-induced YAP/TAZ activation. Importantly, TP activation promotes DNA synthesis and cell migration in VSMCs in a manner dependent on YAP/TAZ. Taken together, thromboxane A2 signaling activates YAP/TAZ to promote VSMC migration and proliferation, indicating YAP/TAZ as potential therapeutic targets for cardiovascular diseases.
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