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4,4′-bis(diphenylphosphinyloxyl) diphenyl ketoxime and 4-diphenyl phospholoxy benzyl alcohol were designed and prepared as supports for peptide synthesis. The total synthesis of cyclic peptides in a resin-free manner was successfully demonstrated.

Photo-sensitive probes based on coumarin deserve extensive attention because of their high biocompatibility, quantum yield, and stability. The synthesis of coumarin and its derivatives is mainly based on four classical methods: Perkin synthesis, Knoevenagel synthesis, Wittig synthesis, and Pechmann synthesis. As everyone knows, fluorescent probes consist of a recognition group, a bridging group, and a luminescent group. Mechanism of fluorescent probes can be roughly summarized into four models: Chelation-induced enhanced fluorescence (CHEF), intramolecular charge transfer (ICT), photoinduced electron transfer (PET), and aggregation-induced luminescence (AIE), which can instruct the design of coumarin-based photo-sensitive probes. Since the fluorescence-based probe was first reported, probes based on coumarin have found widespread application in analytical chemistry, proving to be a selective, efficient, and convenient tool in ion monitoring, molecular monitoring, cell imaging, drug delivery, and many other fields. In this critical review, the synthetic routes of these compounds and the design for fluorescent probes were reported. Furthermore, the recent researches on the employment of coumarin in analytical chemistry were also introduced. Finally, the future research trends and application foreground of coumarin derivatives were forecasted herein.

In this paper, a series of novel tri(4-benzoylphenyl) phosphate derivatives with unique precipitation-inducing properties were synthesized and used as C-terminal supports for peptide synthesis. Mediated and assisted by tri(4-benzoylphenyl) phosphate derivatives, intermediate and target peptides could be separated conveniently via precipitation, which was likely to occur and was conducive to the rapid purification of the intermediates of peptide synthesis without the time-consuming and high-cost process of chromatographic separation and/or recrystallization. Based on these small-molecule supports, both Fmoc and Boc strategies for efficient peptide synthesis via the processes of liquid reaction and solid precipitation were proposed and demonstrated. Due to the peptide synthesis supports developed herein combined with the higher loading performance (loading value 3 mol/1 mol support) and the easily recyclable nature, and the processes of liquid reaction and solid precipitation combining the merits of both liquid-phase peptide synthesis and solid-phase peptide synthesis, a high-yielding, scalable, atom-economical and environment-friendly method of peptide synthesis was developed. The innovative method holds great promise in the fields of organic chemistry and chemical biology research, especially in peptide-based biomedical material and drug synthesis.

A high-efficiency strategy for resin-free and large scale liquid phase synthesis of the anti-SARS octapeptide AVLQSGFR is described. Herein, tri(4'-diphenylphosphonyloxylbenzoyl phenyl)phosphate (TDPBP) derivatives were designed as C-terminal supports to aid octapeptide intermediate purification without the need for chromatographic separation. Furthermore, the ACE inhibitory structure-activity relationship (SAR) of the anti-SARS octapeptide and its alanine-scanning analogues was systematically studied by in vitro assay and 3D-QSAR via molecular docking. This paper provides a new strategy for the development of peptide-based drugs. Simultaneously, a study on the ACE inhibition and structure-activity relationship of the anti-SARS octapeptide also lays a foundation for further understanding how the anti-SARS octapeptide acts as an ACE inhibitor.

We designed and fabricated a novel high throughput brain-on-chip with three dimensional structure with the aim to simulate the in vivo three-dimensional growth environment for brain tissues. The chip consists of a porous filter and 3D brain cell particles, and is loaded into a conventional 96-well plate for use. The filter and the particle molds were fabricated by using computer modeling, 3D printing of positive mold and agarose-PDMS double reversal mold. The 3D cell particles were made by pouring and solidifying a suspension of mouse embryonic brain cells with sodium alginate into a cell particle mold, and then cutting the resulting hydrogel into pieces. The loaded brain-on-chip was used to determine the neurotoxicity of pesticides. The cell particles were exposed to 0, 10, 30, 50, 100 and 200 µmol/L of chlorpyrifos or imidacloprid, separated conveniently from the medium by removing the porous filter after cultivation. Subsequently, cell proliferation, acetylcholinesterase activity and lactate dehydrogenase release were determined for toxicity evaluation. The embryonic brain cells were able to grow and proliferate normally in the hydrogel particles loaded into the filter in a 96-well plate. Pesticide neurotoxicity test showed that both chlorpyrifos and imidacloprid presented dose-dependent inhibition on cell growth and proliferation. Moreover, the pesticides showed inhibition on acetylcholinesterase activity and increase release of lactate dehydrogenase. However, the effect of imidacloprid was significantly weaker than that of chlorpyrifos. In conclusion, a novel brain-on-chip was developed in this study, which can be used to efficiently assess the drug neurotoxicity, pharmacodynamics, and disease mechanism by combining with a microtiterplate reader.

To achieve the synthesis of head-to-tail cyclic peptides via the liquid-phase on-support cyclization and synergistic self-cleavage strategy, 4,4’-bis(diphenylphosphinyloxyl) diphenyl ketoxime (BDKO) and 4-diphenyl phospholoxy benzyl alcohol (DPBA) were designed and prepared as small-molecular supports for greener peptide synthesis. During liquid-phase peptide synthesis on BDKO (or DPBA) support for peptide chain extension by Boc protocol, the last amino acid at the N-terminus of the peptide chain ends with a Fmoc protected amino acid. With the removal of the Fmoc group, head-to-tail cyclization and self-cleavage of the peptide chain synchronously occurred on BDKO (or DPBA) support to release the target cyclic peptide and the original support itself. They can be easily separated and purified, and the support can be recycled for reusing directly. The total synthesis of naturally occurring cyclic peptides such as Mortiamide A-E, Gramicidin S and cyclo(Phe-Pro) on BDKO (or DPBA) support in a resin-free manner was successfully demonstrated.

The tri(4'-diphenylphosphonyloxylbenzoyl phenyl) phosphate (TDPBP) derivatives were designed and developed as C-terminal supports to aid the greener and highefficient liquid-phase peptide synthesis (LPPS) without the need of unrecyclable resin and chromatographic separation, whereby the anti-SARS octapeptide (2) (AVLQSGFR) was synthesized with TDPBP-OH support via Fmoc chemistry and support-aided precipitation (SAP) technology. Furthermore, the ACE inhibition and the inhibitory structure-activity relationship (SAR) between the synthetic C-terminal amidated derivate (1), anti-SARS octapeptide (2) and its alanine-scanning sequence analogues (3) to (9) were systematically studied by HPLC analysis and 3D-QSAR via molecular docking.

To seek the novel application of organophosphorus compounds, the designed tri(4-formylphenyl) phosphonate (TFP) derivatives were successfully synthesized herein, which were used as C-terminal protecting groups of amino acid or greener triple-equivalent supports in liquid-phase peptide synthesis (LPPS). Through the support-aided precipitation effect of TFP derivatives, the peptide intermediates during peptide synthesis were separated and collected via rapid precipitation and facile filtration without chromatographic purification. Furthermore, the TFP derivative support can be directly recycled for reuse without further regeneration after being sheared from the target peptide.

Plecanatide is an oral guanylate cyclase-C agonist for the treatment of gastrointestinal disorders. The large-scale supply of plecanatide is restrained primarily by its industrial manufacture. Herein we developed diphenylphosphinyloxyl diphenyl ketone (DDK) derivatives as greener supports with unique precipitation-inducing properties to aid the liquid-phase total synthesis of plecanatide without the use of chromatography. Plecanatide could be obtained in high yield, and the ultimately sheared DDK derivative residue could be directly recycled or regenerated for reuse.

Nanosheet BiOI materials were synthesized using the precipitation-hydrothermal method. Subsequently, nanoparticle AgI/BiOI nanosheet composites were fabricated using an ion-exchange method and a controlled amount of BiOI. The phase composition, optical morphology, and absorption properties of the samples were determined using XRD, SEM, XPS, TEM, HRTEM, BET, and UV–Vis diffuse reflectance. Organic dyes, such as methyl orange (MO) and Coomassie brilliant blue R-250 (CBB), were used to check the composites’ photocatalytic performance undergoing photodegradation in visible light. The prepared composites had high purity, and the AgI nanoparticles were evenly loaded on the flower-like BiOI nanosheets, both absorbing the visible light. The 50% AgI NP/BiOI NS compound demonstrated the best visible photocatalytic activity and degraded rate of 96.9% and 97% of the MO and CBB dye, respectively, under visible light for 30 ​min. The photocatalytic activity of sole BiOI or AgI was poor, whereas the composites were much better. The composite with 50% AgI exhibited the best photocatalytic activity because of the formation of a heterojunction, which promotes the separation of photogenerated carriers, making AgI stable under visible-light irradiation.

Ternary compound photocatalyst (Cr2S3-GO/TiO2 composite) was prepared by combining graphene oxide (GO) and titanium oxide (TiO2) via sol–gel technique. This synthesized composite was characterized by various methods of analysis (XPS, XRD, SEM, EDX, BET, TGA and TEM). The as-synthesized composite exhibited enhanced photocatalytic performance and degradation rate yielded 98.3, 96.6 and 86.3% on methylene blue, rhodamine B and methyl orange, respectively, under the visible light for 120 min. Cr2S3-GO/TiO2 composite achieved the best photocatalytic activity with 0.3 mol of TiO2. This might be due to the collaborative interaction between increased defects of graphene oxide and photocatalytic effect of Cr2S3. Kinetic model data best fitted with pseudo-first-order model with regression coefficient values of R2 ≥ 0.96. This provides a good opportunity for increased photocatalytic activity in the treatment of wastewater from organic pollutants.

The metal hydrides have great potential for the storage and utilization of hydrogen. Because of the strong exothermic/endothermic effect of H 2 absorption/desorption process, the structure development of metal hydride reactor should mainly focus on the heat transfer enhancement. The new spiral mini-channel reactor is proposed to increase the heat transfer efficiency and H 2 absorption rate. The spiral tubes can not only eliminate the stress produced by temperature changes and volumetric expansions, but also improve the turbulent intensity and heat transfer rate. The numerical model of spiral mini-channel reactor is established, and the simulation results present that the new reactor shows high thermal efficiency and hydrogenation rate. The structure parameters of the reactor are optimized as minor radius of 2.2 mm, axial pitch of 5 mm, major radius of 5.5 mm and tube amount of 3. Furthermore, the operation conditions are investigated. The result indicates that superior performance is obtained for the packing fraction of 0.6 and H 2 pressure over 10 atm during H 2 absorption. With these promising features, this new spiral mini-channel reactor has broad prospects in the hydrogen energy field.

SIJMMARY Melatonin deficiency in cerebrospinal fluid has been postulated to be critical for the development of Alzheimer Disease (AD). As a potent free radical scavengers and antioxidant, melatonin has been proposed to delay or inhibit progression of neurodegeneration in AD. Since the effect of melatonin on AP peptide toxicity in the rat oxidative stress model of AD is not fully understood, we observed the effect of melatonin on AP protein and APP mRNA in the hippocampus and frontal cortex of AD rats model established by Bennett and found melatonin inhibited the AP and APP mRNA . The effect of melatonin could be partly attenuated by pretreatment with the GABA antagonist bicuculline. The results suggest melatonin reduced the AP production probably by inhibiting overexpression of APP in the CNS of AD model rats. Maybe these effects of melatonin were influenced by GABA.

To observe the change of the gene expression of N-methyl-D-aspartate receptors (NMDAR) subunits in rat hippocampus after scalding.The backs of the rats were shaved and immersed in warm water for 10 sec. to make control group (C), and the backs shaved and immersed in hot water (90 degrees C) for 10 sec to make 30% full skin scalding model as the scalding group (S). The mRNA expression of the subunits of rat hippocampus NMDAR-NMDAR1, NMDAR2A, NMDAR2B, NMDAR2D was determined with RT-PCR technique in C group and at 0.5, 1, 2 and 4 postburn hours (PBHs) in S group.(1) There exhibited no obvious change of the mRNA expression of all the subunits of NMDAR at 0.5 and 1 PBH in S group when compared with that in C group. But the mRNA expression of NMDAR1 increased for 24.3% and 20.9% and that of NMDAR2A increased for 27.8% and 27.6% at 2 and 4 PBHs respectively when compared with that in C group (P0.05). In addition, the mRNA expression of NMDAR2B and NMDAR2D revealed no change after scalding.The receptor channel constructed by NMDAR1/NMDAR2A demonstrated increased mRNA expression at 2 PBH, which might lead to the further opening of NMDAR after scalding which might participate in the maladjustment of HPA axis during scalding stress and the following pathophysiological changes.