Latest ArticlesRho-associated coiled-coil-containing protein kinase (ROCK) belongs to the serine-threonine family, and ROCK is involved in a variety of biological processes including cell migration, adhesion, proliferation and differentiation through phosphorylation of different downstream substrates. The aberrant activation of ROCK is associated with the pathological conditions in different systems including various diseases, including cancer, neurological diseases, inflammation, cardiovascular diseases and glaucoma. Therefore, the ROCK inhibitors have potential applicability for treating the aforementioned diseases. Four small molecule ROCK inhibitors have been approved for clinical use: fasudil, ripasudil, netarsudil and belumosudil. In recent years, more small molecule ROCK inhibitors have been identified. This paper reviews the ROCK inhibitors reported in past seven years. We mainly focused on the summarization of the structure–activity relationships, inhibitory efficacy, pharmacological mechanisms and the relevant clinical studies of the reported ROCK inhibitors. Besides the small molecular inhibitors, the peptides and biological extracts which exhibit ROCK inhibitory effects are also included. We also provide suggestions for the future development of the potent ROCK inhibitors.
Researchers engrossed in enantioseparation keep seeking for versatile chiral separation selectors. This work proposes a concept of quasi-dual-chiral-channel (QDCC) enantioseparation platform, where the surface sequentially grafted quinine (QN) and functional cyclodextrin (CD) can imitate two independent chiral channels without mutual interference to achieve wide spectrum chiral resolution. Chiral separation results combined with molecular docking simulation indicates that the different interaction mode of QN and functional CD layer renders QDCC the wide separation capability. This work provides a valuable insight into the rational design of versatile enantioseparation materials.
A novel BINOL-based fluorescence probe (S)-6 featuring a sodium sulfonate fragment at the 2′-position was designed and synthesized via simple synthetic procedures under mild reaction conditions. The water-soluble probe (S)-6 displays excellent enantioselective recognition toward 15 common amino acids, and it can be used for enantiomeric excess determination of amino acids. The fluorescence intensity of (S)-6 treated with amino acids reaches the maximum after standing for only 30 min at room temperature and remains stable in the following 5.5 h, which has great potential in the application of chiral fluorescence analysis due to its timeliness and outstanding fluorescent stability.
Poly(m-phthaloyl-m-phenylenediamine) (PMIA) is promising as the separator in lithium-ion batteries (LIBs) for its excellent thermostability, insulation and self-extinguishing properties. However, its low mechanical strength and poor electrolyte affinity limit its application in LIBs. In this work, a new PMIA@polyacrylonitrile-polyvinylidene fluoride hexafluoropropylene-titanium dioxide (PMIA@PAN/PVDF-HFP/TiO2) composite fibrous separator with a coaxial core-shell structure was developed by combining coaxial electrospinning, hot pressing, and heat treatment techniques. This separator not only inherits the exceptional thermostability of PMIA, showing no evident thermal shrinkage at 220 ℃, but also reveals improved mechanical strength (29.7 MPa) due to the formation of firm connections between fibers with the melted PVDF-HFP. Meanwhile, the massive polar groups in PVDF-HFP play a vital role in improving the electrolyte affinity, which renders the separator a high ionic conductivity of 1.36 × 10−3 S/cm. Therefore, the LIBs with PMIA@PAN/PVDF-HFP/TiO2 separators exhibited excellent cycling and rate performance at 25 ℃, and a high capacity retention rate (76.2%) at 80 ℃ for 200 cycles at 1 C. Besides, the lithium metal symmetric battery assembled by the separator showed a small overpotential, indicating that the separator had a role in inhibiting lithium dendrites. In short, the PMIA@PAN/PVDF-HFP/TiO2 separator possesses a wide application prospect in the domain of LIBs.
Replicating extraordinarily high membrane transport selectivity of protein channels in artificial channel is a challenging task. In this work, we demonstrate that a strategic application of steric code-based social self-sorting offers a novel means to enhance ion transport selectivities of artificial ion channels, alongside with boosted ion transport activities. More specifically, two types of mutually compatible sterically bulky groups (benzo-crown ether and tert-butyl group) were appended onto a monopeptide-based scaffold, which can order the bulky groups onto the same side of a one-dimensionally aligned H-bonded structure. Strong steric repulsions among the same type of bulky groups (either benzo-crown ethers or tert-butyl groups), which are forced into proximity by H-bonds, favor the formation of hetero-oligomeric ensembles that carry an alternative arrangement of sterically compatible benzo-crown ethers and tert-butyl groups, rather than homo-oligomeric ensembles containing a single type of either benzo-crown ethers or tert-butyl groups. Coupled with side chain tuning, this social self-sorting strategy delivers highly active hetero-oligomeric K+-selective ion channel (5F12·BF12)n, displaying the highest K+/Na+ selectivity of 20.1 among artificial potassium channels and an excellent EC50 value of 0.50 µmol/L (0.62 mol% relative to lipids) in terms of single channel concentration
Electrode materials with strong desalting ability is an important research direction of capacitive deionization. In this study, HKUST-1 was successfully synthesized by the solvothermal method, and MOFs-derived porous carbon/Cu@Cu2O composites were prepared by simple pyrolysis as cathode materials for CDI. After high-temperature pyrolysis, the Cu+ site with unsaturated coordination is generated, and the structure changes from micropores to the coexistence of mesoporous and micropores. The complex pore structure is conducive to strengthening ion migration and diffusion. The results show that the porous carbon/Cu@Cu2O materials derived from MOFs depend on the pseudocapacitance behavior for capacitive deionization and desalination. At a voltage window of -1.2 V~1.2 V, a current density of 40 mA/g, and 5 mmol/L NaCl, the HDC-1100 exhibited the best desalting capacity of 30.9 mg/g. HDC-1100 also has good cycle stability. After 20 cycles of adsorption and desorption, the desalting capacity almost does not decrease. Therefore, MOFs derived porous carbon/Cu@Cu2O composites are expected to be an excellent choice for CDI cathode materials.
Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity, exhibiting a wide of biological properties, especially for the lactam derivatives consisting a γ-lactam moiety and N-linked side chains. These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways. Stachbotrydial (2) with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines. In the present work, an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono- and diamines in the fungus Stachybotrys chartarum cultures. In total, 24 phenylspirodrimane lactams (1, 3–25) including 18 new compounds were synthesized. Among them, stachybocin A (1), a bioactive phenylspirodrimane lactam dimer, was produced with the yield of 18.7 mg/g of cell dry weight. The structures of these compounds were elucidated by extensive spectroscopic data, single-crystal X-ray diffraction (Cu Kα), and calculated electronic circular dichroism (ECD) analyses. Bioassay revealed that compounds 1, 17, and 24 displayed significant inhibitory effect on the inactivated state of hNaV 1.2 channels with IC50 values of 0.22, 2.08, and 0.53 µmol/L, respectively. In addition, 1 showed potent protein tyrosine phosphatase 1B (PTP1B) inhibitory, N-methyl-D-aspartate (NMDA) receptor antagonistic, and anti-inflammatory activities.
To improve operation efficiency, an interlayered thin-film composite forward osmosis (iTFC-FO) membrane was designed by introducing an ultrathin and porous interlayer based on aluminum tetra-(4-carboxyphenyl)porphyrin (a stable metal−organic framework nanosheet, Al-MOF). Surface characterization results revealed that Al-MOF spread evenly in the macro-porous substrate, and provided a flat and smooth reaction interface with moderate hydrophilicity and uniform small aperture. The resultant polyamide (PA) layer had a thin base (without intrusion into substrate) and crumpled surface (with abundant leaves). The leaves size and cross-linking degree of PA layer firstly increased and then decreased with the Al-MOF loading. Compared to the original membrane, the iTFC-FO showed an enhanced water permeability and a reduced reverse sodium flux in both modes of active layer facing feed solution (AL-FS) and active layer facing draw solution (AL-DS). To be specific, the specific reverse sodium flux (reverse sodium flux/pure water flux) decreased from 0.27 g/L to 0.04 g/L in the AL-FS mode, while from 1.36 g/L to 0.23 g/L in the AL-DS mode with 2 mol/L NaCl as DS. Moreover, the iTFC-FO maintained high stability and high permeability under high-salinity and contaminated environment. This study offers a new possibility for the rational fabrication of high-performance TFC-FO membranes.
Because of the widespread applications of optically active alkyl fluorides in medicinal and agro chemicals, enantioselective and even stereodivergent construction of alkyl fluorides remains highly desirable but underdeveloped. Transition-metal-catalyzed asymmetric hydrofluoroalkylation of readily available dienes represents a novel route to achieve this goal, yet receives scarce study. Here we report an intriguing palladium-catalyzed enantioselective hydromonofluoroalkylation reaction of conjugated dienes. Both monosubstituted and internal dienes proceed well with the transformation and furnish alkyl fluorides in generally > 80% yield and > 90% ee. A stereodivergent hydromonofluoroalkylation protocol via Pd/Cu co-catalysis is also established for the access to all four stereoisomers of corresponding moieties bearing a fully-substituted F-stereogenic center and vicinal tertiary carbon center. In addition, asymmetric migratory hydromonofluoroalkylation of skipped dienes is developed to realize the direct allylic CH fluoroalkylation. A compound library of enantioenriched cyclic fluorides is thus built to highlight the transformation potential of present methodology.
The deterioration of water caused by industrial production is a thorny problem. Solving the problem cogently through innovative coagulationstrategies has been recognized of important practical significance. In this work, a simple enhanced coagulation by using ferric chloride (FC) and poly-ferric chloride (PFC) coupled with polyamidine (PA) were tried to remove the toxic organics. The results shown that PA addition could obviously enhance coagulation performances of the iron-based coagulants. The synergic coagulation process and mechanism were studied and discussed in detail based on the coagulation behaviors, flocs properties, removal efficiency and zeta potentials. FC and PFC remove organics mainly through charge neutralization and adsorption-bridging, resulting in a good purification performance. While PA with a higher charge density showed better purification performance due to enhanced charge neutralization. It is worth mentioning that the addition of PA could make the coagulants adapt to a wider pH range, and remove the toxic organics more effectively. That is to say, the practical adaptability of the coagulant was enhanced. This work thus provides a simple strategy to effectively purify wastewater and further improve the water safety.
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