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Extracellular vesicles (EVs) have now been recognized as important mediators of cellular communication during injury and repair. We previously found that plasma EVs isolated from ex vivo perfused human lungs injured with Escherichia coli bacterial pneumonia were inflammatory, and exogenous administration of high molecular weight (HMW) hyaluronic acid (HA) as therapy bound to these EVs, decreasing inflammation and injury. In the current study, we studied the role of EVs released during severe Pseudomonas aeruginosa (PA) pneumonia in mice and determined whether intravenous administration of exogenous HMW HA would have therapeutic effects against the bacterial pneumonia. EVs were collected from the bronchoalveolar lavage fluid (BALF) of mice infected with PA103 by ultracentrifugation and analyzed by NanoSight and flow cytometry. In a cytotoxicity assay, administration of EVs released from infected mice (I-EVs) decreased the viability of A549 cells compared to EV isolated from sham control mice (C-EVs). Both exogenous HMW HA or an anti-CD44 antibody, when co-incubated with I-EVs, significantly improved the viability of the A549 cells. In mice with PA103 pneumonia, administration of HMW HA improved pulmonary edema and bacterial count in the lungs and decreased TNF-α and caspase-3 levels in the supernatant of lung homogenates. In conclusion, EVs isolated from BALF of mice with Pseudomonas aeruginosa pneumonia were cytotoxic and inflammatory, and intravenous HMW HA administration was protective against Pseudomonas aeruginosa pneumonia.

Bacterial sample preparation is crucial for its observation by scanning electron microscopy (SEM). However, the current polylysine (PLL) method leads to bacterial morphological changes. To overcome this problem, we employed chitosan (CS) to coat coverslips to prepare bacteria for SEM and compared it with the PLL method. Coverslips coated with 0.025% (w/v) CS showed satisfactory bacterial binding ability. Within 30 min of binding time, the number of bacteria on CS-coated and PLL-coated coverslips exhibited no differences. Four bacteria strains were employed to compare the differences in SEM images between the two methods. Most of the bacteria showed irregular surface or sticky substances after settling on PLL-coated coverslips, while bacteria with clear surface texture were observed on CS-coated coverslips. Transmission electron microscopy (TEM) images showed deformed bacterial envelope on PLL-coated coverslips; meanwhile, similar intact envelope was observed from the bacteria on CS-coated coverslips and the bacteria without any treatment. The TEM results verified the morphological differences of SEM between the two methods. Except for morphology, the length of the rod-shaped bacteria was longer on CS-coated coverslips than that on PLL-coated coverslips, less shrinkage of the sample was observed, and CS could preserve the length of the rod-shaped bacteria better than PLL in its preparation for SEM. It is demonstrated that the low-cost CS could be utilized in bacterial preparation for SEM to acquire preferable images. Bacterial suspension with optical density at 600 nm of about 0.5, deposited on 0.025% CS-coated coverslips for 30 min, and followed by routine fixation, dehydration, and drying are optimal parameters.

Ginsenoside compound K (CK) is the major intestinal bacterial metabolite of ginsenosides that exhibits anticancer potential in various cancer cells both in vitro and in vivo. The anticancer types, mechanisms, and effects of CK in the past decade have been summarized in this review. Briefly, CK exerts anticancer effects via multiple molecular mechanisms, including the inhibition of proliferation, invasion, and migration, the induction of apoptosis and autophagy, and anti-angiogenesis. Some signaling pathways play a significant role in related processes, such as PI3K/Akt/mTOR, JNK/MAPK pathway, and reactive oxygen species (ROS). Moreover, the effects of CK combined with nanocarriers for anticancer efficiency are discussed in this review. Furthermore, we aimed to review the research progress of CK against cancer in the past decade, which might provide theoretical support and effective reference for further research on the medicinal value of small molecules, such as CK.

Anthocyanins are important pigments that contribute to fruit quality. The regulation of anthocyanin biosynthesis by several transcription factors via sophisticated regulatory networks has been studied in various plants. Brassinosteroids (BRs), a new class of plant hormone, are involved in regulating anthocyanin biosynthesis in fruits. Furthermore, light directly affects the synthesis and distribution of anthocyanins. Here, we summarize the recent progress toward understanding the impact of BR and light on anthocyanin biosynthesis in climacteric and non-climacteric fruits. We review the BR and light signaling pathways and highlight the important transcription factors that are associated with the synthesis of anthocyanins, such as BZR1 (brassinazole-resistant 1, BR signaling pathway), HY5 (elongated hypocotyl 5) and COP1 (constitutively photomorphogenic 1, light signal transduction pathway), which bind with the target genes involved in anthocyanin synthesis. In addition, we review the mechanism by which light signals interact with hormonal signals to regulate anthocyanin biosynthesis.

Helical polymers present some interesting and distinctive properties, and one of the most distinguished applications of them is the chiral recognition and resolution of enantiomers. In this work, star-shaped hybrid helical poly (phenyl isocyanide) (PPI) with polyhedral oligomeric silsesquioxanes (POSS) as the core was designed and synthesized by "grafting to" strategy. The homoarm star-shaped hybrid POSS-(PPI)8 was first obtained by the click reaction between azide-modified POSS (POSS-(N3 )8 ) and alkynyl-modified PPI (PPI-Alkynyl). The hybrid POSS-(PPI)8 was with predominated left-handed helical conformation and exhibited excellent ability in the enantioselective crystallization of racemic compounds. In the meantime, heteroarm star-shaped hybrid (PEG)4 -POSS-(PPI)4 was prepared by the click reaction of POSS-(N3 )8 with PPI-Alkynyl and alkynyl-modified poly (ethylene glycol) (PEG-Alkynyl). The hybrid (PEG)4 -POSS-(PPI)4 was amphiphilic, and it could self-assemble to form spherical micelles in aqueous solutions.

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease threatening the health of the elderly, but the available therapeutic and preventive drugs remain suboptimal. Loganin, an iridoid glycoside extracted from Cornus officinalis, is reported to have anti-inflammatory and memory-enhancing properties. This study is aimed to explore the influence of loganin on cognitive function in 3xTg-AD mice and the underlying mechanism associated with its neuroprotection. According to the results of behavioral tests, we found that administration of loganin could significantly alleviate anxiety behavior and improve memory deficits of 3xTg-AD mice. Furthermore, immunohistochemical analysis displayed that there were decreased Aβ deposition in the hippocampus and cortex of 3xTg-AD mice treated with loganin compared with the control mice. Importantly, the Aβ-related pathological change was mainly involved in altering APP expression and processing. And loganin was also found to reduce the levels of phosphorylated tau (i.e. pTauS396 and pTauS262) in 3xTg-AD mice. By performing 2D-DIGE combined with MALDI-TOF-MS/MS, we revealed 28 differentially expressed proteins in the 3xTg-AD mice treated with loganin compared with the control mice. Notably, 10 proteins largely involved in energy metabolism, synaptic proteins, inflammatory response, and ATP binding were simultaneously detected in 3xTg-AD mice compared to WT mice. The abnormal changes of energy metabolism (PAGM1 and ENO1), synaptic proteins (SYN2 and Cplx2), inflammatory response (1433Z) were verified by western blot. Overall, our study suggested that loganin could be used as a feasible candidate drug to ameliorate molecular deficits, pathologies and cognitive impairment for prevention and treatment of AD.

Sanguinarine (SAN) and chelerythrine (CHE) have significant anti-inflammatory and growth-promoting activities and have been widely used in medicine and stockbreeding. However, SAN and CHE are present in only small amounts (0.5% capsule dry weight) in the Chinese herbal medicine Macleaya cordata, resulting in a consistently high price of their derivative products. Here, we generated transgenic plants overexpressing the key SAN and CHE biosynthetic pathway gene, protopine-6-hydroxylase (P6H), via genetic transformation. Quantitative detection by ultra-performance liquid chromatography tandem/triple quadrupole mass spectrometry (UPLC-QQQ-MS) showed that the contents of SAN and CHE increased in the overexpressing plants compared with the wild-type plants. Moreover, these plants had a higher relative expression of level of McP6H in the roots, stems and leaves, and the relative expression of the downstream enzyme dihydrobenzophenanthridine oxidase (McDBOX) also increased significantly. These results indicate that overexpression of the P6H gene is a promising approach to improve SAN and CHE production and is significant in the study of the synthesis pathways of benzylisoquinoline alkaloids (BIAs) to obtain germplasm resources with high alkaloid contents.

Microbial sulfate reduction is largely associated with anaerobic methane oxidation and alkane degradation in sulfate-methane transition zone (SMTZ) of deep-sea cold seeps. How the sulfur cycling is mediated by microbes near SMTZ has not been fully understood. In this study, we detected a shallow SMTZ in three of eight sediment cores sampled from two cold seep areas in the South China Sea. One hundred ten genomes representing sulfur-oxidizing bacteria (SOB) and sulfur-reducing bacteria (SRB) strains were identified from three SMTZ-bearing cores. In the layers above SMTZ, SOB were mostly constituted by Campylobacterota, Gammaproteobacteria and Alphaproteobacteria that probably depended on nitrogen oxides and/or oxygen for oxidation of sulfide and thiosulfate in near-surface sediment layers. In the layers below the SMTZ, the deltaproteobacterial SRB genomes and metatranscriptomes revealed CO2 fixation by Wood-Ljungdahl pathway, sulfate reduction and nitrogen fixation for syntrophic or fermentative lifestyle. A total of 68% of the metagenome assembled genomes were not adjacent to known species in a phylogenomic tree, indicating a high diversity of bacteria involved in sulfur cycling. With the large number of genomes for SOB and SRB, our study uncovers the microbial populations that potentially mediate sulfur metabolism and associated carbon and nitrogen cycles, which sheds light on complex biogeochemical processes in deep-sea environments.

Potassium-selenium (K-Se) batteries have attracted significant attention as one of the most promising alternatives of lithium-ion storage systems owing to high energy density and low cost. In the design of Se-based cathode materials, however, the low utilization rate of active Se and the rapid dissolution of polyselenides seriously weaken the capacity and cycle stability. Therefore, how to make full use of Se species without loss during the charge and discharge process is the key to design high-performance Se-based cathode. In this paper, a 3D “water cube”-like Se/C hybrid (denoted as Se−O−PCS) is constructed with the assistance of Na2CO3 templates. Thanks to the abundant carbonate groups (CO32−) originated from the Na2CO3 templates, the molten Se species are firmly anchored into the pore of carbon skeleton by strong C−O−Se bonding. Thus, this unique Se−O−PCS model not only improves the utilization of active Se species, but also can reduce the contact with the electrolyte to inhibit the shuttle effect of polyselenides. Moreover, flexible carbon skeleton gives Se-O-PCS hybrid a good electrical conductivity and excellent structural robustness. Consequently, the resultant Se−O−PCS hybrid is endowed with an obviously enhanced K-ions storage property.

Rate coefficients for the reaction of NO 3 radicals with a series of aromatic aldehydes were measured in a 7300 L simulation chamber at ambient temperature and pressure by relative and absolute methods. The rate coefficients for benzaldehyde (BA), ortho-tolualdehyde (O-TA), meta-tolualdehyde (M-TA), para-tolualdehyde (P-TA), 2,4-dimethyl benzaldehyde (2,4-DMBA), 2,5-dimethyl benzaldehyde (2,5-DMBA) and 3,5-dimethyl benzaldehyde (3,5-DMBA) were k1= 2.6 ± 0.3, k2= 8.7 ± 0.8, k3= 4.9 ± 0.5, k4= 4.9 ± 0.4, k5= 15.1 ± 1.3, k6= 12.8 ± 1.2 and k7= 6.2 ± 0.6, respectively, in the units of 10 −15 cm 3 molec. −1 s −1 at 298 ± 2 K. The rate coefficient k13 for the reaction of the NO 3 radical with deuterated benzaldehyde (benzaldehyde-d 1) was found to be half that of k1 . The end product of the reaction in an excess of NO 2 was measured to be C 6 H 5 C(O)O 2 NO 2 . Theoretical calculations of aldehydic bond energies and reaction pathways indicate that the NO 3 radical reacts primarily with aromatic aldehydes through the abstraction of an aldehydic hydrogen atom. The atmospheric implications of the measured rate coefficients are briefly discussed.

Plants must maintain a balance between their carbon (C) supply and utilization during the day–night cycle for continuous growth since C starvation often causes irreversible damage to crop production. It is not well known how C fixation and allocation in the leaves of crops such as maize adapt to sudden environmental changes. Here, to quantify primary C fixation and partitioning in photosynthetic maize leaves under extended darkness and to relate these factors to plant growth, maize seedlings were subjected to extended darkness (ED) for three successive days at the 6th leaf fully expanded stage (V6). ED reduced plant growth and leaf chlorophyll levels but not the rate of net CO2 exchange. As a result of the reduction in photoassimilates, the accumulation of starch and total soluble carbohydrates (TSC) in mature leaves also decreased under ED. However, the percentage of the daily C fixation reserved in mature leaves increased. These transient C pools were largely composed of TSC and were mainly used for consumption by increased nocturnal respiration rather than for transport. As the days went on, both the amount of C accumulated and the percentage of the daily fixed C that was reserved in leaves decreased, which could be largely accounted for by the attenuated starch synthesis in all treatments. The activities of ADP-glucose pyrophosphorylase and soluble starch synthase decreased significantly over time. Therefore, this study concluded that both starch and TSC are involved in the coordination of the C supply and plant growth under a sudden C shortage but that they may be involved in different ways. While the ratio of reserved C to daily fixed C increased to maintain blade function under acute C starvation, both the amount and the proportion of C reserved in mature leaves decreased as plant growth continued in order to meet the growth demands of the plant.

Palladium/BuAd2P efficiently catalyzed the direct α-arylation of ketone in the anti-Alzheimer's disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridinyl analogue (12) shows significantly lower toxicity compared to donepezil and remarkable neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. Docking results of compound 12 also interpreted the possible mechanism of the selective inhibition between AChE and butyrylcholinesterase (BuChE).

The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of N-(hetero)aryl analogues (1-32) of the natural anti-Alzheimer's disease drug huperzine A (HPA) was prepared via palladium-catalyzed Buchwald-Hartwig cross-coupling reactions of HPA with various aryl bromides in good yields. Most of the N-aryl-huperzine A (N-aryl-HPA) analogues showed good acetylcholinesterase (AChE) inhibitory activity in in vitro experiments. Three arylated huperzine A analogues (14, 19, and 30) exhibited stronger anti-AChE activity than HPA. The 5-methoxy-2-pyridyl analogue (30) displayed the most potent AChE inhibition activity, with an IC50 value of 1.5 μM, which was 7.6-fold more active than HPA. Compound 30 also exhibited better neuroprotective activity for H2O2-induced damage in SH-SY5Y cells than HPA. Structure-activity relationship analysis suggested that the electron density of the installed aromatic ring or heteroaromatic ring played a significant role in inducing the AChE inhibition activity. Overall, compound 30 showed the advantages of easy synthesis, high potency and selectivity, and improved neuroprotection, making it a potential huperzine-type lead compound for Alzheimer's disease drug development.

Lightweight and elastic carbon aerogels (CAs) are promising candidates for use in the development of pressure sensors and electromagnetic interference (EMI) shielding materials. However, the development of a simple strategy for the fabrication of CAs with the properties of high compression and excellent fatigue resistance is still significantly challenging. In this study, Pickering emulsion gel technology, which depends on the aqueous dispersion of cellulose nanofibrils (CNF), graphene oxide (GO), and 1, 2-dichloroethane solution of polymethyl methacrylate (PMMA) that occurs in mixture, emulsification, gelation, and freeze-drying process, was used to form a CNF-GO/PMMA composite aerogel. Subsequently, the final carbon aerogel (C-RGO/P) was obtained through annealing treatment. The resultant C-RGO/P exhibits super compressibility and excellent elasticity, and can resist an extreme compressive strain of 99.3% while maintaining 92.6% of the height retention after 5000 cycles at the strain of 80%. Additionally, it exhibits high sensitivity at the working pressure range of 0–1000 Pa, and can thus act as a wearable pressure sensor for the accurate monitoring of human physiological signals. Moreover, it can be used as an EMI shielding material with satisfactory EMI shielding effectiveness (SE) of 36.75 dB and specific shielding effectiveness (SSE) of 29400 dB cm3 g−1.

Bone defect is usually difficult to recover quickly, and bone scaffold transplantation is considered to be an effective method. Biomaterials have a wide range of application prospects in bone tissue repair, and the two key problems are the selection of materials and cells. The object of this study was to discuss the structural characteristics of bone scaffold materials and their effects on bone repair in vivo. The chitin-hydroxyapatite (HAP)-collagen composite scaffolds (CHCS) was prepared with epichlorohydrin (ECH) as crosslinking agent. The structure was characterized and the compressive strength, porosity, water absorbency and stability were investigated. The biocompatibility and osteogenic differentiation of CHCS in vitro were detected, and the effect of defect repair in vivo was evaluated. The results suggested that HAP not only enhanced the compressive strength of CHCS, but also promoted the formation of calcium nodules due to its bone conductivity. Histological staining showed that collagen promoted collagen deposition and new bone formation. X-ray images also indicated that CHCS transplantation accelerated bone repair. Therefore, CHCs has immense potential in bone regeneration.

Here we report a nonenzymatic glycosylation reaction that builds axial S-glycosidic bonds under biorelevant conditions. This strategy is enabled by the design and use of allyl glycosyl sulfones as precursors to glycosyl radicals and exploits the exceptional functional group tolerance of radical processes. Our method introduces a variety of unprotected glycosyl units to the cysteine residues of peptides in a highly selective fashion. Through developing the second-generation protocol, we applied our method in the direct glycosylation of complex polypeptides and proteins. Computational studies were performed to elucidate the reaction mechanism.

Purpose: Ongoing clinical trials show limited efficacy for Chimeric antigen receptor (CAR) T treatment for acute myeloid leukemia (AML). The aim of this study was to identify potential causes of the reported limited efficacy from CAR-T therapies against AML. Experimental Design: We generated CAR-T cells targeting Epithelial cell adhesion molecule (EpCAM) and evaluated their killing activity against AML cells. We examined the impacts of modulating mTORC1 and mTORC2 signaling in CAR-T cells in terms of CXCR4 levels. We examined the effects of a rapamycin pretreatment of EpCAM CAR-T cells (during ex vivo expansion) and assessed the in vivo antitumor efficacy of rapamycin-pretreated EpCAM CAR-T cells (including CXCR4 knockdown cells) and CD33 CAR-T cells in leukemia xenograft mouse models. Results: EpCAM CAR-T exhibited killing activity against AML cells but failed to eliminate AML cells in bone marrow. Subsequent investigations revealed that aberrantly activated mTORC1 signaling in CAR-T cells results in decreased bone marrow infiltration and decreased the levels of the rapamycin target CXCR4. Attenuating mTORC1 activity with the rapamycin pretreatment increased the capacity of CAR-T cells to infiltrate bone marrow and enhanced the extent of bone marrow AML cell elimination in leukemia xenograft mouse models. CXCR4 knockdown experiments showed that CXCR4 contributes to the enhanced bone marrow infiltration capacity of EpCAM CAR-T cells and the observed reduction in bone marrow AML cells. Conclusions: Our study reveals a potential cause for the limited efficacy of CAR-T reported from current AML clinical trials and illustrates an easy-to-implement pretreatment strategy, which enhances the anti-AML efficacy of CAR-T cells. See related commentary by Maiti and Daver, p. 5739

BackgroundBiochemical recurrence is defined as only rising CA-125 but no radiographic evidence of disease; noteworthily, it generally precedes the onset of clinical evidence. Now treatment strategies of biochemical recurrence ovarian cancer (OC) remain controversial. Apatinib as monotherapy or in combination with other chemotherapeutic agents has shown its effect in the treatment of some advanced malignancies. In our study, we focused on the efficacy of apatinib in recurrent OC, especially its clinical activity in biochemical-only recurrent OC patients.MethodsWe retrospectively analyzed clinical material of 41 recurrent patients who had received apatinib monotherapy or apatinib plus chemotherapy between June 2016 and August 2018. Apatinib was administered at a 500mg daily dose. Response was determined according to measurable disease or serum carbohydrate antigen (CA)-125 levels. Progression-free survival (PFS) was estimated by Kaplan–Meier method.ResultsAll patients were evaluable, 19 (46.34%) had biochemical relapse and 22 (53.66%) had clinical relapse. The objective response rate (ORR) and disease control rate (DCR) in the overall population were 31.71% and 78.05%, respectively. The median PFS was 7 months (95% confidence interval 5.43–8.57). And in patients with biochemical-only relapse, the median PFS was 6 months, with ORR of 26.32% and DCR of 89.47%.ConclusionsApatinib is a well-tolerated and effective agent to delay clinical progression of patients with biochemical-only recurrent OC. More important, our study shows the promising prospect for treating OC patients with asymptomatic biochemical relapse.

Background Previous clinical trials have demonstrated that entinostat in combination with exemestane had good tolerability and significant clinical efficacy in patients with advanced hormone receptor positive (HR+) and HER2 negative (HER2−) metastatic breast cancer (MBC) in the USA. However, no clinical trials have been conducted in Chinese populations. Objective To investigate the safety, pharmacokinetics, and pilot efficacy of entinostat with or without exemestane in Chinese postmenopausal patients with locally advanced or metastatic HR+ /HER2− MBC. Patients and methods Nineteen patients received entinostat for 4 weeks (dose-limiting toxicity (DLT) observation stage) at 3, 5, or 7 mg/week, with a “3+3” dose-escalation design and in combination with exemestane thereafter (extended treatment stage: entinostat, 3 or 5 mg/week; exemestane, 25 mg/day). An additional 21 patients were enrolled to assess the entinostat (5 mg) plus exemestane (25 mg) pharmacokinetic profile and potential efficacy. Results The peak entinostat serum concentration and area under the curve increased dose proportionally, without significant interaction between entinostat and exemestane. Entinostat was well tolerated at all doses. The most common grade 3/4 adverse effects (AEs) included neutropenia (31.6%) and thrombocytopenia (15.8%). In the DLT observation stage, grade 3/4 AEs accounted for 16.7% in the 5 mg group with one suspicious DLT (G3 ventricular tachycardia) and 33.3% in the 7 mg group. In the extended treatment stage, 2/16 patients achieved partial response and three patients experienced stable disease (> 12 weeks). The median progression-free survival was 9.41 months for the additional 21 patients, who experienced grade 3/4 AEs of neutropenia (38%), thrombocytopenia (9.5%), anemia (9.5%), and fatigue (9.5%). Conclusion Entinostat with exemestane showed reasonable safety, tolerability, and encouraging efficacy in Chinese patients with HR+/HER2− MBC. These results support further evaluation in a randomized, double-blind Phase III study with a weekly 5 mg entinostat dose in a Chinese population. Trial Registration NCT02833155.

Carbon nitride, as one of the metal-free photocatalysts, has aroused wide attention due to its low cost, easy preparation, and excellent optical response. However, challenges of the high recombination rate of electron-hole pair hindered their potential applications. Here, boron-doped carbon nitride nanotubes were designed and prepared by a simple hydrothermal and calcination route. Compared with the bulk carbon nitride, the control strategy forms the ordered nanotube structure, which greatly improved their specific surface area, exposed more active sites, and enhanced the graphitization degree. The transient fluorescence lifetime of tubular carbon nitride is twice as long as that of pure carbon nitride. Furthermore, boron doping carbon nitride nanotubes exhibited a 1.5-fold increase in a lifetime over tubular carbon nitride, which acts a synergistic role with nanotube architecture to further increases the carrier concentration and hinder the recombination of photogenerated electron-hole. Under the irradiation of visible light, the amount of hydrogen evolution of the optimum photocatalyst has achieved 22.1 mmol g−1 h−1, which was 64 times that of the bulk carbon nitride and exhibited excellent stability. This work provides a promising strategy for the development of non-metallic doped carbon nitride nanotube photocatalysts for hydrogen evolution. The project was funded by National Natural Science Foundation of China (Nos. 21901154, 21671129), the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT17R71).

Objectives: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. Methods: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1–7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. Results: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. Conclusions: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in patients with ARDS compared with healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control ( GGPPSfl/fl) and myeloid-selective knockout ( GGPPSfl/fl LysMcre) mice were then generated. Interestingly, using an LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency upregulated the production of LPS-induced IL-6, IL-1β, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.

Two new premyrsinane-type diterpenes (2 and 3) as diastereomers were synthesized from lathyrane-type diterpene euphorbia factor L3 (1) for the first time via an efficient Fe(acac)3-catalyzed skeleton conversion process. This conversion features a biogenetically inspired strategy that relies on a concise reductive olefin coupling involving intramolecular Michael addition with free radicals. The structures of 2 and 3 were elucidated by a combination of the interpretation of their spectroscopic data and single-crystal X-ray diffraction analysis. The premyrsinane diterpenes 2 and 3 exhibited cytotoxic activity against the 4T1 breast cancer cell line, while the parent compound euphorbia factor L3 (1) was inactive. The current results not only confirmed the biogenetic relationship between lathyranes and premyrsinanes for the first time but also suggested a novel method for the preparation of naturally rare premyrsinane diterpenes with high bioactivity from the more abundant natural lathyrane diterpenes.

BCL-XL, an antiapoptotic member of the BCL-2 family of proteins, drives tumor survival and maintenance and thus represents a key target for cancer treatment. Herein we report the rational design of a novel series of selective BCL-XL inhibitors exemplified by A-1293102. This molecule contains structural elements of selective BCL-XL inhibitor A-1155463 and the dual BCL-XL/BCL-2 inhibitors ABT-737 and navitoclax, while representing a distinct pharmacophore as assessed by an objective cheminformatic evaluation. A-1293102 exhibited picomolar binding affinity to BCL-XL and both efficiently and selectively killed BCL-XL-dependent tumor cells. X-ray crystallographic analysis demonstrated a key hydrogen bonding network in the P2 binding pocket of BCL-XL, while the bent-back moiety achieved efficient occupancy of the P4 pocket in a manner similar to that of navitoclax. A-1293102 represents one of the few distinct structural series of selective BCL-XL inhibitors, and thus serves as a useful tool for biological studies as well as a lead compound for further optimization.

Background Although promising, clinical translation of human mesenchymal stem or stromal cell-derived extracellular vesicles (MSC EV) for acute lung injury is potentially limited by significant production costs. The current study was performed to determine whether pretreatment of MSC EV with high molecular weight hyaluronic acid (HMW HA) would increase the therapeutic potency of MSC EV in severe bacterial pneumonia. Methods In vitro experiments were performed to determine the binding affinity of HMW HA to MSC EV and its uptake by human monocytes, and whether HMW HA primed MSC EV would increase bacterial phagocytosis by the monocytes. In addition, the role of CD44 receptor on MSC EV in the therapeutic effects of HMW HA primed MSC EV were investigated. In Pseudomonas aeruginosa (PA) pneumonia in mice, MSC EV primed with or without HMW HA were instilled intravenously 4 h after injury. After 24 h, the bronchoalveolar lavage fluid, blood, and lungs were analyzed for levels of bacteria, inflammation, MSC EV trafficking, and lung pathology. Results MSC EV bound preferentially to HMW HA at a molecular weight of 1.0 MDa compared with HA with a molecular weight of 40 KDa or 1.5 MDa. HMW HA primed MSC EV further increased MSC EV uptake and bacterial phagocytosis by monocytes compared to treatment with MSC EV alone. In PA pneumonia in mice, instillation of HMW HA primed MSC EV further reduced inflammation and decreased the bacterial load by enhancing the trafficking of MSC EV to the injured alveolus. CD44 siRNA pretreatment of MSC EV prior to incubation with HMW HA eliminated its trafficking to the alveolus and therapeutic effects. Conclusions HMW HA primed MSC EV significantly increased the potency of MSC EV in PA pneumonia in part by enhancing the trafficking of MSC EV to the sites of inflammation via the CD44 receptor on MSC EV which was associated with increased antimicrobial activity.

Selumetinib (ARRY-142886) is a potent, selective, MEK1/2 inhibitor approved in the US for the treatment of children (≥ 2 years) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). We characterized population pharmacokinetics (PK) of selumetinib and its active N‐desmethyl metabolite, evaluated exposure–safety/efficacy relationships, and assessed the proposed therapeutic dose of 25 mg/m2 bid based on body surface area (BSA) in this patient population. Population PK modeling and covariate analysis (demographics, formulation, liver enzymes, BSA, patients/healthy volunteers) were based on pooled PK data from adult healthy volunteers (n = 391), adult oncology patients (n = 83) and pediatric patients with NF1-PN (n = 68). Longitudinal selumetinib/metabolite exposures were predicted with the final model. Exposure–safety/efficacy analyses were applied to pediatric patients (dose levels: 20, 25, 30 mg/m2 bid). Selumetinib and metabolite concentration–time courses were modeled using a joint compartmental model. Typical selumetinib plasma clearance was 11.6 L/h (95% CI 11.0–12.2 L/ h). Only BSA had a clinically relevant (> 20%) impact on exposure, supporting BSA-based administration in children. Selumetinib and metabolite exposures in responders (≥ 20% PN volume decrease from baseline) and non-responders were largely overlapping, with medians numerically higher in responders. No clear relationships between exposure and safety events were established; exposure was not associated with key adverse events (AEs) including rash acneiform, diarrhea, vomiting, and nausea. Findings support continuous selumetinib 25 mg/m2 bid in pediatric patients. Importantly, the updated dosing nomogram ensures that patients will receive a clinically active, yet tolerable, dose regardless of differences in BSA and allows dose reductions, if necessary.

AIM: To investigate the effects of nicotinamide (NAM) on bevacizumab (BEV)-induced epithelial-mesenchymal transition (EMT) of human retinal pigment epithelial cells (ARPE-19) and the underling mechanisms. METHODS: ARPE-19 cells were treated with BEV for 24, 48, and 72h, and the variation degrees of EMT-related markers (fibronectin, α-SMA, vimentin, and ZO-1) were assessed by Western blotting to select the optimal treatment time point which exhibited the most obvious changes of EMT-related markers for the subsequent experiments. Furthermore, NAM was added to the medium, the mRNA and protein levels of the EMT-related markers were then measured. The accumulation of reactive oxygen species (ROS) and H2O2 and the total antioxidant capacity (TAC) of the cells were also measured to evaluate the level of oxidative stress. RESULTS: After being treated with BEV for 72h, the protein expression levels of EMT-related markers in ARPE-19 cells showed significant changes. Meanwhile the levels of ROS and H2O2 were obviously increased, and the TAC of ARPE-19 cells was decreased. Totally 72h was chosen to be the optimal treatment time point in subsequent experiments. Furthermore, NAM inhibited BEV-induced EMT by downregulating fibronectin, α-SMA, and vimentin and upregulating ZO-1, decreased the accumulation of ROS and H2O2, and enhanced TAC in BEV-treated ARPE-19 cells. CONCLUSION: This study demonstrates that NAM suppressed BEV-induced EMT in ARPE-19 cells by attenuating oxidative stress. Hence, NAM may be a potential therapeutic agent for alleviating neovascular fibrosis of the ocular fundus after anti-vascular endothelial growth factor therapy.

Perchlorate, emerging pollution with thyroid toxicity, has a high detection rate in fresh tea leaves. What needs attention is that the uptake characteristic is insufficiently understood. Herein, the uptake, accumulation, and translocation of perchlorate in a tea plant-hydroponic solution system were investigated, of which the mechanism was further lucubrated by subcellular distribution. The perchlorate concentration in tea tissues is ramped up along with the increase in the exposure level and time. The bioaccumulation factor of tea tissues followed the rank: mature leaves > tender leaves > roots. After the seedlings have been transplanted to a perchlorate-free solution, the perchlorate in mature leaves is reduced significantly, accompanied by a progressive increase in perchlorate in new shoots and solutions. The cell-soluble fractions are the major reservoir of perchlorate both for roots (>59%) and leaves (>76%), which precisely explained the translocation within the tea plant-hydroponic solution system. These results not only illuminate the uptake characteristic in tea plants but also improve the understanding of the behavior of perchlorate in higher plants.

Hang Zhou,1,2,* Jiawei Sun,1,* Jiaqi Wu,1 Hong Wei,1 Xianli Zhou1 1In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Ultrasound, Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianli ZhouIn-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of ChinaTel/Fax +86-0451-86605362Email hrbzhouxl@163.comBackground: The specific microenvironment of solid tumors, which is characterized by hypoxia, overexpression of glutathione (GSH), and high accumulation of anti-inflammatory tumor-associated macrophages (TAMs), limits the efficiency of sonodynamic therapy (SDT).Method and Results: Herein, a multifunctional nanoplatform was engineered to modulate the tumor microenvironment for highly efficient SDT. In this system, sonosensitizers and catalase were encapsulated in disulfide-bridged mesoporous organosilicon nanoparticles with high loading, which protected the activity of catalase and ensure the stability of sonosensitizers and enzyme. Subsequently, hyaluronic acid was grafted onto the nanoplatform to reeducate TAMs and induce the secretion of exogenous hydrogen peroxide. Due to the good protection of enzyme, the catalase within the nanoplatform efficiently produced the mount of O2 through decomposing the hydrogen peroxide in tumor tissues, which remarkably alleviated tumor hypoxia. Furthermore, degradation of the nanoparticles was observed in response to GSH, which effectively decreased the intracellular GSH level, further favoring SDT-triggered anticancer effect.Conclusion: Based on the multiple adjustments to tumor microenvironment, our nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.Keywords: sonodynamic therapy, hypoxia, tumor-associated macrophages, catalase, glutathione depletion

Aim: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population. Methods: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography–tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke. Results: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P < 0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend < 0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension. Conclusions: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.

Lead-free organic–inorganic hybrid materials have attracted wide interest due to their excellent optoelectronic and photovoltaic properties. Herein, we synthesized a Bi-based hybrid material with one-dimensional (1D) Bi-I anionic chains, namely, (C5H9N2)[BiI4] (1) by solvothermal method. Single-crystal X-ray diffraction analysis reveals that it crystallizes in monoclinic space group of C2/c with the cell parameters a = 15.539(13) A, b = 13.860(12) A, c = 7.789(6) A, β = 117.02(2)o, V = 1494(2) A3, and Z = 4, which is composed of protonated 1,3-dimethylimidazolium cations and one-dimensional (1D) [BiI4]∞− chains interconnected via edge-sharing μ2-I. This compound exhibits fast degradation of rhodamine B (RhB) at room temperature under dark condition.

PURPOSE Mucosal melanoma (MM) is a highly vascularized tumor with an extremely poor prognosis. In this randomized, open-label, phase II study, we characterized the efficacy and safety of bevacizumab in combination with carboplatin plus paclitaxel (CPB) in patients with previously untreated advanced MM. PATIENTS AND METHODS Patients were randomly assigned in a 2:1 ratio to receive carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m2) once every 4 weeks in combination with (CPB arm, 5 mg/kg) or without (CP arm) bevacizumab once every 2 weeks. Progression-free survival (PFS) was the primary end point. Secondary end points included overall survival (OS), objective response rate, and adverse events. RESULTS We recruited 114 patients to our study. The median PFS was significantly longer in the CPB arm (4.8 months; 95% CI, 3.6 to 6.0 months) than in the CP arm (3.0 months; 95% CI, 1.7 to 4.3 months) (hazard ratio, 0.461; 95% CI, 0.306 to 0.695; P < .001). Objective response rates were 19.7% and 13.2%, respectively ( P = .384). The median OS was also significantly longer in the CPB arm than in the CP arm (13.6 v 9.0 months; hazard ratio, 0.611; 95% CI, 0.407 to 0.917; P = .017). No new safety signals were observed. CONCLUSION PFS and OS were significantly better in patients with metastatic MM who received bevacizumab in addition to CPB than in those who received CPB alone. A phase III study should be performed to confirm these benefits (ClinicalTrials.gov identifier: NCT02023710 ).

Although the combination of chemotherapy and immunotherapy is a hot topic in lung cancer, little is understood regarding the possible mechanisms behind their synergy. Moreover, safety is a major concern for clinicians while performing chemotherapy. Therefore, it is important to determine the appropriate dose and period of chemotherapy for combining it with immunotherapy, and investigate the underlying synergistic mechanism. Here, we showed that carboplatin can induce DNA damage and activate the canonical STING/TBK1/IRF3 pathway and non-canonical STING-NF-κB signaling complex. Further, low-dose carboplatin changed the "cold" tumor into a "hot" tumor via the signaling hub STING, augmenting CD8+ T-cell infiltration, increasing PD-L1 expression, and hence potentiating the anti-tumor effect of PD-1 inhibitors; importantly, there were no adverse effects. Furthermore, knocking down STING in tumor cells effectively reversed PD-L1 upregulation and STING pathway activation, and reduced the anti-tumor effect of low-dose carboplatin and carboplatin-PD-1 inhibitor combination. Our findings collectively reported a previously unexplored role of low-dose carboplatin targeting in the STING pathway and provided an economical, useful and safe option for improving the efficacy of PD-1 inhibitors in lung cancer.

Chronic bacterial-infected wound healing/skin regeneration remains a challenge due to drug resistance and the poor quality of wound repair. The ideal strategy is combating bacterial infection, while facilitating satisfactory wound healing. However, the reported strategy hardly achieves these two goals simultaneously without the help of antibiotics or bioactive molecules. In this work, a two-dimensional (2D) Ti3C2Tx MXene with excellent conductivity, biocompatibility, and antibacterial ability was applied in developing multifunctional scaffolds (HPEM) for methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. HPEM scaffolds were fabricated by the reaction between the poly(glycerol-ethylenimine), Ti3C2Tx MXene@polydopamine (MXene@PDA) nanosheets, and oxidized hyaluronic acid (HCHO). HPEM scaffolds presented multifunctional properties containing self-healing behavior, electrical conductivity, tissue-adhesive feature, antibacterial activity especially for MRSA resistant to many commonly used antibiotics (antibacterial efficiency was 99.03%), and rapid hemostatic capability. HPEM scaffolds enhanced the proliferation of normal skin cells with negligible toxicity. Additionally, HPEM scaffolds obviously accelerated the MRSA-infected wound healing (wound closure ratio was 96.31%) by efficient anti-inflammation effects, promoting cell proliferation, and the angiogenic process, stimulating granulation tissue formation, collagen deposition, vascular endothelial differentiation, and angiogenesis. This study indicates the important role of multifunctional 2D MXene@PDA nanosheets in infected wound healing. HPEM scaffolds with multifunctional properties provide a potential strategy for MRSA-infected wound healing/skin regeneration.

Here, we show that benproperine phosphate (BPP), a cough suppressant, triggers AMPK/mTOR‐mediated autophagy initiation and disturbs Ras‐related protein Rab‐11A (RAB11A)‐mediated autophagosome–lysosome fusion, resulting in excessive accumulation of autophagosomes in pancreatic cancer (PC) cells. Inhibition of autophagy or overexpression of RAB11A partially reverses BPP‐induced growth inhibition in PC cells, suggesting BPP as a potent anti‐PC agent via the induction of autophagy arrest., Pancreatic cancer (PC) is one of the most common human malignancies worldwide and remains a major clinical challenge. Here, we found that benproperine phosphate (BPP), a cough suppressant, showed a significant anticancer effect on PC both in vitro and in vivo via the induction of autophagy‐mediated cell death. Mechanistic studies revealed that BPP triggered AMPK/mTOR‐mediated autophagy initiation and disturbed Ras‐related protein Rab‐11A (RAB11A)‐mediated autophagosome–lysosome fusion, resulting in excessive accumulation of autophagosomes. Inhibition of autophagy or overexpression of RAB11A partially reversed BPP‐induced growth inhibition in PC cells, suggesting that BPP might induce lethal autophagy arrest in PC cells. In conclusion, our results identify BPP as a potent antitumor agent for PC via the induction of autophagy arrest, therefore providing a new potential therapeutic strategy for the treatment of PC.

Lipid metabolism disorder and inflammatory response are considered to be the major causes of atherosclerogenesis. Astragalin, the most important functional component of flavonoid obtained from persimmon leaves, has the hypolipidemic effects. However, it is unknown, how astragalin protects against atherosclerosis. The aim of this study was to observe the effects of astragalin on cholesterol efflux and inflammatory response and to explore the underlying mechanisms. Our results showed that astragalin upregulated the expression of ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1), promoted cholesterol efflux, and suppressed foam cell formation. Inhibition of the PPARγ/LXRα pathway abrogated the promotive effects of astragalin on both transporter expression and cholesterol efflux. In addition, treatment of astragalin markedly decreased the secretion of inflammatory factors, including interleukin 6, monocyte chemotactic protein 1, tumor necrosis factor α, and interleukin 1β. Mechanistically, astragalin upregulated ABCA1 and ABCG1 expression, which in turn reduced TLR4 surface levels and inhibited NF-κB nuclear translocation. Consistently, astragalin reduced atherosclerotic plaque area in apoE-/- mice. Taken together, these findings suggest that astragalin protects against atherosclerosis by promoting ABCA1- and ABCG1-mediated cholesterol efflux and inhibiting proinflammatory mediator release.

Facile synthesis of high optically active helical polymers from achiral monomers still remains a great challenge. In this work, two chiral Ni(II) catalysts bearing chiral R- or S-2a ligands were facilely prepared which can efficiently initiate the living/controlled polymerization of allene monomers and afford well-defined polyallenes in high yields with controlled molecular masses (Mₙs) and low molecular mass distributions (Mw/Mₙs). The catalysts showed interesting regioselectivity on the cumulated double bonds of allene monomers, as the polymerizations were highly selective which occurred on 2,3-double bonds. Moreover, the polymerization of achiral allene monomers using chiral Ni(II) catalysts showed remarkable helix-sense selectivity. The yielded polyallenes exhibited high optical activity due to the formation of a predominant one-handed helix as revealed by circular dichroism, UV–vis, and direct atomic force microscopy (AFM) observations as well. The predominant one-handed helicity of the generated polyallenes was solely determined by the chirality of the Ni(II) catalysts.

The isoselective ring-opening polymerization of racemic lactide was achieved by combining N-heterocyclic olefin (NHO) with mono(thio)ureas or bis(thio)ureas as catalytic systems. The polymerization process shows high stereoselectivity, controllability and reactivity, delivering multi-block isotactic polylactides with high chain-end fidelity and narrow molecular weight distributions. The enhancement of catalytic performance was observed in the following order: bisthiourea (DTU) < monothiourea (TU) < bisurea (DU) < urea (U). The highest Pm (probability of forming a meso dyad) = 0.91 was observed at −70 °C when using NHO/U1 catalytic system and the high stereoselectivity was attributed to chain-end control mechanism.

Goldfish comprise around 300 different strains with drastically altered and aesthetical morphologies making them suitable models for evolutionary developmental biology. The dragon-eye strain is characterized by protruding eyes (analogous to those of Chinese dragons). Although the strain has been selected for about 400 years, the mechanism of its eye development remains unclear. In this study, a stable dragon-eye goldfish strain with a clear genetic background was rapidly established and studied. We found that upregulation of the PPAR signaling pathway accompanied by an increase in lipid accumulation might trigger the morphological and structural transformation of the eye in dragon-eye goldfish. At the developmental stage of proptosis (eye protrusion), downregulation of the phototransduction pathway was consistent with the structural defects and myopia of the dragon-eye strain. With the impairment of retinal development, cytokine-induced inflammation was activated, especially after proptosis, similar to the pathologic symptoms of many human ocular diseases. In addition, differentially expressed transcription factors were significantly enriched in the PAX and homeobox families, two well-known transcription factor families involved in eye development. Therefore, our findings reveal the dynamic changes in key pathways during eye development in dragon-eye goldfish, and provide insights into the molecular mechanisms underlying drastically altered eyes in goldfish and human ocular disease.

A stable Co(II)-based metal–organic framework (MOF) was constructed by applying a dual ligand strategy. The ultra-stable Co(II) MOF, [Co(H3tpb)(Hbtc)]n (1), was obtained by hydrothermal reaction of a novel trimer pyrazole ligand H3tpb and a classic carboxylic ligand H3btc (H3tpb = 1,3,5-tris (pyrazolyl) benzene, H3btc = 1,3,5-benzoic acid). In addition, complex 1 shows photocatalytic activity for the degradation of the dyes methylene blue (MB) and methyl orange (MO) under UV light. About 83.8% MB and 75.3% MO could be removed within 150 min. Serial experiments were performed to evaluate the biological activity of this compound in neonatal sepsis and explore its related mechanism. The results of the ELISA showed that the compound could reduce the releasing of the inflammatory cytokines in a dose-dependent manner. Besides, the compound could also reduce the relative expression levels of the gram-positive bacterial virulence. Simulations based on the molecular docking found that the complex could form multiple hydrogen bonds with several residues in the domain pocket.

Polyallene is one of the most attractive synthetic precursors for constructing functional materials due to its unsaturated bonds on the main chain or pendants. The facile synthesis of high regioselectivity polyallenes still remains a challenge. In this work, a novel Ni(II) catalyst with a phosphine bearing sulfoxide moiety named Ming-Phos (L4) as a ligand was developed to initiate the polymerization of various allene monomers efficiently in a fast and living/controlled manner. The well-defined polyallenes were afforded in high yields with a controlled molar mass (Mn) and low molar mass distribution (Mw/Mn). Moreover, the Ni(II)/L4 catalyst exhibited fascinating regioselectivity on the accumulated double bonds of allene monomers, and the 2,3-regioselectivity of the polymerization of allene monomers was up to >99.9%. Remarkably, various monomers with different functional groups inculding alkyl, alkoxy and substituted phenyl groups could be polymerized effectively using Ni(II)/L4 as the initiator, affording polyallenes with higher 2,3-regioselectivity. The regioselectivity, and thermodynamic and crystallization properties of the polyallenes were confirmed by 1H NMR, DSC, TGA and WAXD, respectively.

Polyhedral oligomeric silsesquioxane (POSS) based starlike hybrid helical poly(phenyl isocyanide)s (PPIs) with well-defined structures were designed and prepared in this contribution. The POSS modified with Pd(II) complexes (POSS-Pd(II)) was firstly obtained. Then well-defined starlike hybrid helical PPIs with POSS cores were synthesized through the polymerization of phenyl isocyanide monomers using POSS-Pd(II) as the initiator. The polymerization proceeded in a living and controlled manner. Meanwhile, polymerization of chiral phenyl isocyanides with decyl chain modified pendant L- or D-alanine afforded optically active hybrid starlike helical PPIs with preferred handedness. What's more, amphiphilic starlike hybrid helical PPI block copolymers showing thermoresponses were easily obtained, and their self-assembly and thermo-responsive behaviours were studied. In addition, cross-linked hybrid helical PPIs were obtained via the transesterification reaction between pentafluorophenyl ester and cystamine. Benefitting from the essential chirality of the handed helical PPIs, the cross-linked hybrid PPIs showed excellent ability in the enantioselective crystallization of racemic compounds. The enantiomeric excess (ee) of the induced crystal of threonine could be up to 95%.

A highly efficient and controllable ring-opening polymerization of lactones (δ-valerolactone, e-caprolactone and rac-lactide) has been achieved by using N-heterocyclic olefin (NHO) and thiourea/urea (TU/U) catalytic systems. This catalytic system showed high ring-opening activity and stereoselectivity, delivering biodegradable polyesters with high chain-end fidelity, controlled molecular weights and narrow molar mass dispersities. A detailed investigation of the structure–activity relationship was performed by exploring five NHOs and fourteen TUs/Us. For a fixed NHO, when the acidity of TUs/Us decreases, the polymerization mechanism changes from the (thio)urea anion to the neutral cooperative activation mode, and the catalytic activity first increases and then decreases, displaying a highly effective interval. For a given TU or U, as the basicity of NHOs increases, the catalytic performance improves correspondingly. Besides, highly isoselective ROP of rac-LA (Pm = 0.93) at −78 °C has been also achieved, highlighting the versatility of the NHO/TU(U) system. These findings enrich the type of TU/U and base organocatalyst.

Herein, a novel pathway to prepare a porous structured DNA hybrid hydrogel has been described, using a transiently existing Pickering emulsion that is continuously generated during the reaction. The as-prepared highly porous gel features significantly improved capability for trace amounts of PAH removal.

Sanguinarine (SAN) and chelerythrine (CHE) have been widely used as substitutes for antibiotics for decades. For a long time, SAN and CHE have been extracted from mainly Macleaya cordata, a plant species that is a traditional herb in China and belongs to the Papaveraceae family. However, with the sharp increase in demand for SAN and CHE, it is necessary to develop a new method to enhance the supply of raw materials. Here, we used methyl jasmonate (MJ), salicylic acid (SA) and wounding alone and in combination to stimulate aseptic seedlings of M. cordata at 0 h, 24 h, 72 h and 120 h and then compared the differences in metabolic profiles and gene expression. Ultimately, we found that the effect of using MJ alone was the best treatment, with the contents of SAN and CHE increasing by 10- and 14-fold, respectively. However, the increased SAN and CHE contents in response to combined wounding and MJ were less than those for induced by the treatment with MJ alone. Additionally, after MJ treatment, SAN and CHE biosynthetic pathway genes, such as those encoding the protopine 6-hydroxylase and dihydrobenzophenanthridine oxidase enzymes, were highly expressed, which is consistent with the accumulation of SAN and CHE. At the same time, we have also studied the changes in the content of synthetic intermediates of SAN and CHE after elicitor induction. This study is the first systematic research report about using elicitors to increase the SAN and CHE in Macleaya cordata.

End-functionalization is an effective strategy for fabricating functional materials. Installing functional groups onto the chain end of helical polymers is of great interest. In this paper, we reported a new method for constructing end-functional helical poly(phenyl isocyanide)s. At first, a family of helical polyisocyanides with controlled Mn and low polydispersity bearing a Pd(II) complex on the chain end was readily prepared via the Pd(II)-mediated living polymerization of isocyanide monomers. To activate the terminal Pd(II)-complex, a variety of phosphine ligands were tested. It was found that the ligand exchange of the Pd(II) complex with Wei-phos provides a terminal Pd(II)-complex with high activity, which can promote the Sonogashira coupling reaction with many terminal alkyne derivatives. Taking advantage of this method, a series of interesting functional groups including dansyl chloride, the F atom, and the aldehyde group can be facilely installed onto the end of helical polyisocyanides. Moreover, a couple of hybrid block copolymers can also be obtained via the Sonogashira coupling reaction of the Pd(II)-terminated helical polyisocyanides with different functional polymers such as poly(ethylene glycol) (PEG), poly(L-lactide) (PLLA) and polycaprolactone (PCL) bearing an alkynyl group on the chain end. This method can not only install interesting functionalities onto the chain end of helical polyisocyanides but also remove the transition metal residue simultaneously facilely.