Effect of Penetration Enhancer on the Structure of Stratum Corneum: On-Site Study by Confocal Polarized Raman Imaging.

Keratin and lipid structures in the stratum corneum (SC) are closely related to the SC barrier function. The application of penetration enhancers (PEs) disrupts the structure of SC, thereby promoting infiltration. To quantify these PE-induced structural changes in SC, we used confocal Raman imaging (CRI) and polarized Raman imaging (PRI) to explore the integrity and continuity of keratin and lipid structures in SC. The results showed that water is the safest PE and that oleic acid (OA), sodium dodecyl sulfate (SDS), and low molecular weight protamine (LMWP) disrupted the ordered structure of keratin, while azone and liposomes had less of an effect on keratin. Azone, OA, and SDS also led to significant changes in lipid structure, while LMWP and liposomes had less of an effect. Establishing this non-invasive and efficient strategy will provide new insights into transdermal drug delivery and skin health management.

Carbazolic Conjugated Microporous Polymers for Photocatalytic Organic Transformations.

Heterogeneous photocatalysis have been deemed as a versatile and colorful platform for exploring efficient transformation systems. Henceforth, the design of photocatalysts underpins a wide range of research interests. By virtue of synthetic versatility, stability, non-toxicity, purely organic properties, tunable semiconductive structures, and remarkable visible-light absorbance, conjugated microporous polymers (CMPs) have emerged as an attractive new class of semiconductor materials that show great potential for tackling important energy and environmental challenges. Over the past decade, immense efforts have been devoted toward the construction of CMPs-based photocatalysts for versatile photocatalytic transformations. This review aims to summarize the latest representative advances in the field of carbazolic CMPs, focusing on various design strategies for the construction of tailor-made skeletons that have direct impact on their charge dynamics and thus photocatalytic performances, especially on their specific photocatalytic efficiency for organic transformations. Scrutinizing the photocatalytic features and elucidating the related design principles, it is fully described how structure modification of polycarbazoles could have an effect on optical properties, and thus on photocatalytic performance. Furthermore, the bottlenecks that need to be addressed, and the future research directions of CMPs are identified in the area of photocatalysis.

Effects of polyvinylchloride microplastics on the toxicity of nanoparticles and antibiotics to aerobic granular sludge: Nitrogen removal, microbial community and resistance genes.

Copper oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) have ecological risk to humans and ecosystems. Polyvinylchloride microplastics (PVC MPs), as a representative of microplastics, may often coexist with CuO NPs and CIP in wastewater treatment systems due to their widespread application. However, the co-impact of PVC MPs in wastewater systems contained with CuO NPs and CIP on nitrogen removal and ecological risk is not clear. In this work, PVC MPs co-impacts on the toxicity of CuO NPs and CIP to aerobic granular sludge (AGS) systems and potential mechanisms were investigated. 10 mg/L PVC MPs co-addition did not significantly affect the nitrogen removal, but it definitely changed the microbial community structure and enhanced the propagation and horizontal transfer of antibiotics resistance genes (ARGs). 100 mg/L PVC MPs co-addition resulted in a raise of CuO NP toxicity to the AGS system, but reduced the co-toxicity of CuO NPs and CIP and ARGs expression. The co-impacts with different PVC MPs concentration influenced Cu2+ concentrations, cell membrane integrity, extracellular polymeric substances (EPS) contents and microbial communities in AGS systems, and lead to a change of nitrogen removal.

Fabrication and Decryption of a Microarray of Digital Dithiosuccinimide Oligomers.

Digital polymers with precisely arranged binary units provide an important option for information storage. This is especially true if the digital polymers are assembled in a device, as it would be of great benefit for data writing and reading in practice. Herein, inspired by the DNA microarray technique, the programmable information storing and reading on a mass spectrometry target plate is proposed. First, an array of 4-bit sequence-coded dithiosuccinimide oligomers is efficiently built through sequential thiol-maleimide Michael couplings with good sequence readability by tandem mass spectrometry (MS/MS). Then, toward engineering microarrays for information storage, a programmed robotic arm is specifically designed for precisely loading sequence-coded oligomers onto the target plate, and a decoding software is developed for efficient readout of the data from MS/MS sequencing. Notably, short sequence-coded oligomer chains can be used to write long strings of information, and extra error-correction codes are not required as usual due to the inherent concomitant fragmentation signals. Not only text but also bitimages can be automatically stored and decoded with excellent accuracy. This work provides a promising platform of digital polymers for programmable information storing and reading.

When polymerization meets coordination-driven self-assembly: metallo-supramolecular polymers based on supramolecular coordination complexes.

Polymers have greatly changed and are still changing the way we live ever since, and the construction of novel polymers as functional materials remains an attractive topic in polymer science and related areas. During the past few years, the marriage of discrete supramolecular coordination complexes (SCCs), including two-dimensional (2D) metallacycles and three-dimensional (3D) metallacages, and polymers gave rise to two novel types of metallo-supramolecular polymers, i.e., metallacycle/metallacage-cored star polymers (MSPs) and metallacycle/metallacage-crosslinked polymer networks (MPNs), which has attracted increasing attention and emerged as an exciting new research direction in polymer chemistry. Attributed to their well-defined and diverse topological architectures as well as the unique dynamic features of metallacycles/metallacages as cores or crosslinks, these novel polymers have shown extensive applications. In this review, aiming at providing a practical guide to this emerging area, the introduction of synthetic strategies towards MSPs and MPNs will be presented. In addition, their wide applications in areas such as functional materials, molecular sieving, drug delivery, bacterial killing and bioimaging are also discussed.

A Two-Dimensional Metallacycle Cross-Linked Switchable Polymer for Fast and Highly Efficient Phosphorylated Peptide Enrichment.

The selective and efficient capture of phosphopeptides is critical for comprehensive and in-depth phosphoproteome analysis. Here we report a new switchable two-dimensional (2D) supramolecular polymer that serves as an ideal platform for the enrichment of phosphopeptides. A well-defined, positively charged metallacycle incorporated into the polymer endows the resultant polymer with a high affinity for phosphopeptides. Importantly, the stimuli-responsive nature of the polymer facilitates switchable binding affinity of phosphopeptides, thus resulting in an excellent performance in phosphopeptide enrichment and separation from model proteins. The polymer has a high enrichment capacity (165 mg/g) and detection sensitivity (2 fmol), high enrichment recovery (88%), excellent specificity, and rapid enrichment and separation properties. Additionally, we have demonstrated the capture of phosphopeptides from the tryptic digest of real biosamples, thus illustrating the potential of this polymeric material in phosphoproteomic studies.

Acid-Activated Motion Switching of DB24C8 between Two Discrete Platinum(II) Metallacycles.

The precise operation of molecular motion for constructing complicated mechanically interlocked molecules has received considerable attention and is still an energetic field of supramolecular chemistry. Herein, we reported the construction of two tris[2]pseudorotaxanes metallacycles with acid-base controllable molecular motion through self-sorting strategy and host-guest interaction. Firstly, two hexagonal Pt(II) metallacycles M1 and M2 decorated with different host-guest recognition sites have been constructed via coordination-driven self-assembly strategy. The binding of metallacycles M1 and M2 with dibenzo-24-crown-8 (DB24C8) to form tris[2]pseudorotaxanes complexes TPRM1 and TPRM2 have been investigated. Furthermore, by taking advantage of the strong binding affinity between the protonated metallacycle M2 and DB24C8, the addition of trifluoroacetic acid (TFA) as a stimulus successfully induces an acid-activated motion switching of DB24C8 between the discrete metallacycles M1 and M2. This research not only affords a highly efficient way to construct stimuli-responsive smart supramolecular systems but also offers prospects for precisely control multicomponent cooperative motion.

MF59 adjuvant enhances the immunogenicity and protective immunity of the OmpK/Omp22 fusion protein from Acineterbacter baumannii through intratracheal inoculation in mice.

Acinetobacter baumannii (A baumannii) is an emerging nosocomial pathogenic bacterium which leads to hospital infections. The increase in drug-resistant A baumannii strains makes it difficult to control by using common antibiotics. The development of effective vaccines is an alternative means to avoid A baumannii infections. In the present study, Balb/c mice were inoculated intratracheally with 30 µg of OmpK/Omp22 fusion protein alone or OmpK/Omp22 formulated with MF59 adjuvant. After two times of boosting at day 14 and 21, the antigen-specific antibody levels and the protective immunity against A baumannii challenge were evaluated. The results showed that the OmpK/Omp22 formulated with MF59 immunized mice produced much higher level of antigen-specific antibodies compared to mice immunized with OmpK/Omp22 alone (P < 0.01). Mice immunized with 30 µg of OmpK/Omp22 formulated with MF59 also provided more potent protection post-challenge, which showed lower bacterial loads in the blood and lung tissue, lower level of blood inflammatory cytokines and higher survival rate (83.3%) than mice immunized with OmpK/Omp22 alone (P < 0.001). In conclusion, this study demonstrated that OmpK/Omp22 fusion protein adjuvanted with MF59 induced superior immune response and better protection than OmpK/Omp22 alone through intratracheal inoculation in mice.

[Regression analysis of serum bone metabolic markers and traditional Chinese medicine syndromes in patients with CKD-MBD].

To analyze the interdependent relationship between serum bone metabolic markers and traditional Chinese medicine (TCM) syndromes in patients with chronic kidney disease (stages 3 and 4)-related mineral and bone disorder (CKD-MBD), in order to provide the objective basis for exploring the rules of TCM syndrome differentiation in patients with CKD-MBD. The retrospective survey was conducted to collect 105 cases with CKD (stages 3 and 4)-MBD. General clinical indexes, frequency of TCM syndromes and distribution of TCM syndrome type were investigated. Furthermore, serum bone metabolic markers, including calcium (Ca2+), phosphonium (P3+), intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), procollagen type 1 amino-N-terminal propeptide (P1NP) and ß-crosslaps (ß-CTX) were analyzed, respectively. Meanwhile, bone mineral density (BMD) was assessed. And then, the multivariate regression analysis was performed for serum bone metabolic markers and TCM syndromes. The results showed that the general clinical features of the 105 patients included old age, hypertension, fracture, loss of bone mass and mild abnormalities of serum bone metabolic markers. High-frequency TCM syndromes were related to Yang deficiency in Spleen and Kidney, Qi deficiency in Spleen and Kidney and blood stasis. Moreover, Yang deficiency in Spleen and Kidney and blood stasis were found as the most frequent characteristics of the distribution of TCM syndromes type. The clinical characteristics of patients with the syndrome type of Yang deficiency in Spleen and Kidney were probably old age, increase in TCM syndrome scores and abnormalities in iPTH and P1NP. In addition, the interdependent relationship between abnormality in Ca2+ and syndromes of hair loss, tooth shake and sexual dysfunction, abnormality in P3+ and syndromes of aches in waist and knees, abnormality in iPTH and syndromes of soreness and weakness in waist and knees, lassitude, fatigue and extreme chilliness, abnormality in ALP and syndromes of loose stools, abnormality in P1NP and syndromes of fear of chills, tendency of warmth and loose stools, and abnormality in ß-CTX and syndromes of chills and pain in waist and knees. In general, among the 105 cases with CKD (stages 3 and 4)-MBD were clinically characterized by mild changes in serum bone metabolic markers; And their main TCM syndrome was the deficiency in spleen and kidney. Serum bone metabolic markers with mild changes have an interdependent relationship with main TCM syndromes, and can be considered as an objective syndrome factor of TCM syndrome differentiation.

Mercury mass flow in iron and steel production process and its implications for mercury emission control.

The iron and steel production process is one of the predominant anthropogenic sources of atmospheric mercury emissions worldwide. In this study, field tests were conducted to study mercury emission characteristics and mass flows at two iron and steel plants in China. It was found that low-sulfur flue gas from sintering machines could contribute up to 41% of the total atmospheric mercury emissions, and desulfurization devices could remarkably help reduce the emissions. Coal gas burning accounted for 17%-49% of the total mercury emissions, and therefore the mercury control of coal gas burning, specifically for the power plant burning coal gas to generate electricity, was significantly important. The emissions from limestone and dolomite production and electric furnaces can contribute 29.3% and 4.2% of the total mercury emissions from iron and steel production. More attention should be paid to mercury emissions from these two processes. Blast furnace dust accounted for 27%-36% of the total mercury output for the whole iron and steel production process. The recycling of blast furnace dust could greatly increase the atmospheric mercury emissions and should not be conducted. The mercury emission factors for the coke oven, sintering machine and blast furnace were 0.039-0.047gHg/ton steel, and for the electric furnace it was 0.021gHg/ton steel. The predominant emission species was oxidized mercury, accounting for 59%-73% of total mercury emissions to air.

Caveolin-1 mediates gene transfer and cytotoxicity of polyethyleneimine in mammalian cell lines.

Polyethyleneimine (PEI) is a cost-effective and non-viral vector for gene transfer, but the factors determining gene transfer efficiency and cytotoxicity of PEI in different mammalian cell lines remain largely unknown. In the present study, three different cell lines were chosen for investigation. Using pEGFP DNA and PEI, 21.5, 29.2, and 92.1 % of GFP-positive cells were obtained in BMSC, Hela, and 293T, respectively. In luciferase reporter assay, similar results were obtained (for luciferase activity, BMSC < Hela < 293T cells). By MTT test and cell apoptotic marker analysis, we demonstrated that high gene transfer efficiency is accompanied with high cytotoxicity of PEI. Moreover, we found that high expression level of caveolin-1 was accompanied with high gene transfer efficiency and cytotoxicity of PEI in 293T cells. More convincingly, caveolin-1 silencing in 293T could reduce both gene transfer efficiency and cytotoxicity of PEI. In contrast, caveolin-1 overexpression in BMSCs increases both gene transfer efficiency and cytotoxicity of PEI. Taken together, our study suggests that caveolin-1 may at least in part determine gene transfer efficiency and cytotoxicity of PEI in mammalian cell lines, providing caveolin-1 as a potential target for improving gene transfer efficiency when applying positively charged polyplexes to cell transfection.

Cross-linked supramolecular polymer gels constructed from discrete multi-pillar[5]arene metallacycles and their multiple stimuli-responsive behavior.

A new family of discrete hexakis-pillar[5]arene metallacycles with different sizes have been successfully prepared via coordination-driven self-assembly, which presented very few successful examples of preparation of discrete multiple pillar[n]arene derivatives. These newly designed hexakis-pillar[5]arene metallacycles were well characterized with one-dimensional (1-D) multinuclear NMR ((1)H and (31) P NMR), two-dimensional (2-D) (1)H-(1)H COSY and NOESY, ESI-TOF-MS, elemental analysis, and PM6 semiempirical molecular orbital methods. Furthermore, the host-guest complexation of such hexakis-pillar[5]arene hosts with a series of different neutral ditopic guests G1-6 were well investigated. Through host-guest interactions of hexakis-pillar[5]arene metallacycles H2 or H3 with the neutral dinitrile guest G5, the cross-linked supramolecular polymers H2⊃(G5)3 or H3⊃(G5)3 were successfully constructed at the high-concentration region, respectively. Interestingly, these cross-linked supramolecular polymers transformed into the stable supramolecular gels upon increasing the concentrations to a relatively high level. More importantly, by taking advantage of the dynamic nature of metal-ligand bonds and host-guest interactions, the reversible multiple stimuli-responsive gel-sol phase transitions of such polymer gels were successfully realized under different stimuli, such as temperature, halide, and competitive guest, etc. The mechanism of such multiple stimuli-responsive processes was well illustrated by in situ multinuclear NMR investigation. This research not only provides a highly efficient approach to the preparation of discrete multiple pillar[n]arene derivatives but also presents a new family of multiple stimuli-responsive "smart" soft matters.

Supramolecular DNA nanogels through host-guest interaction for targeted drug delivery.

DNA hydrogels have been demonstrated with the advantages of good stability, easy modification, and extraordinary biocompatibility, which enables their great application prospects in biosensing, tissue engineering, and biomedicine. Based on the host-guest recognition properties of cucurbit[8]uril (CB[8]), we proposed a general method for constructing functional supramolecular DNA nanogels. Guest molecules have been conjugated into the DNA building units, which could be further crosslinked with CB[8] to construct supramolecular DNA nanogels. At the same time, the aptamer has also been modified into the hydrogel network to achieve cell targeting. These supramolecular DNA nanogels have been demonstrated with a controllable size and multiple stimuli responses, in addition to the excellent biocompatibility, stability and good targeting drug transport ability. Such a host-guest based strategy will provide a molecular library as a "toolbox" for the functionalization of DNA nanogels.

Inhibition of EV71 replication by an interferon-stimulated gene product L3HYPDH.

Enterovirus 71 (EV71) is the common causative agent of hand-foot-mouth disease (HFMD). Despite evidence in mice model suggested that the interferon (IFN) signaling pathways play a role in defending against this virus, knowledge on the IFN-mediated antiviral response is still limited. Here we identified an IFN-stimulated gene (ISG) called L3HYPDH, whose expression inhibits EV71 replication. Mapping assay indicated that amino acids 61-120 and 295-354 are critical for its optimal antiviral activity. Mechanismly, L3HYPDH specifically inhibits protein translation mediated by EV71 internal ribosome entry site (IRES). Our data thus uncovered a new mechanism utilized by the host cell to restrict EV71 replication.

[Analysis of the association between cellulose and lignin by carbon 13 tracer method].

In order to further understand the association between cellulose and lignin in gymnosperm plant, carbohydrate part of the lignin-carbohydrate complexes was analyzed. Cellulose precursor, i.e., (6(-13) C) uridine diphoshphate glucose, was synthesized, and injected into a living ginkgo tree with lignin inhibitor AOPP and exogenous lignin precursor. The results from the determination of 13C abundance indicate that the deposition of cellulose in the cell wall is very fast and effective in the primary wall. The analysis of high resolution solid nuclear magnetic 13C NMR spectra confirms that the bonds between C5 position of glucose units in cellulose and alpha-carbons of lignin side chain are benzyl ether linkage.

Cucurbit[7]uril-Based Supramolecular DNA Nanogel for Targeted Codelivery of Chemo/Photodynamic Drugs.

Nanodrug delivery systems for the delivery of combination therapeutics have shown their exceptionally potential clinical application by facilitating better synergistic anticancer effects. Herein, we developed a universal strategy to fabricate supramolecular DNA nanogels from DNA tetrahedron skeleton and cucurbit[7]uril-based host-guest interaction for codelivery the chemo and photodynamic therapy drugs. The constructed supramolecular DNA nanogels showed the size tunability, host-guest competition and DNA enzyme responsibility. The cell uptake and MTT experiments demonstrated that the nanogel has excellent biocompatibility and specificity, and achieved the enrichment and slow release of drug in cells. Finally, the combined chemo/photodynamic therapy was realized by coloading doxorubicin hydrochloride and methylene blue. It was proven to be a better stragety to promote apoptosis of cancer cells compared to single chemotherapy or photodynamic therapy. These results suggest that our proposed supramolecular nanogels have provided an effective nanoplatform for drug delivery in the combinational therapy for cancer.

[Analyzing the Chinese medicine pathogenesis of stroke].

Both ischemic and hemorrhage stroke pertain to the category of wind stroke in Chinese medicine (CM). Up to date, it is deemed that the etiology and pathogenesis of wind stroke are wind, fire, sputum, qi, stasis, and deficiency. Among them, it is regarded that wind and fire are the key factors triggering wind stroke. By analyzing the time order and causality, it is found that wind stroke is prior to the onset of wind and fire, wind and fire are the secondary outcomes of wind stroke. By parallel comparing stroke with thromboembolism and hemorrhagic diseases in other Zang-organs, it can be comprehended that the reason why wind symptoms appear in stroke is due to its physiological feature of brain itself. Based on Neijing, the pathogenesis of wind stroke is proposed as follows. Tunnels of viscera (vessels) get lesions. The old pathogenic factors of sputum and stasis or the stasis formed by bleeding inside viscera consume qi, and blood of viscera and damage the spirits hidden in them. The damage of Gan-spirit causes symptoms of stroke, such as hemiplegia, deviation of eyes and mouth, and so on. Wind and fire symptoms are caused by the injury of Gan blood and yin, and/or the stagnation of fire in pericardium (the pathway organ) due to obstruction by old pathogenic factors and stasis (formed by bleeding).

Type I Interferon-Induced TMEM106A Blocks Attachment of EV-A71 Virus by Interacting With the Membrane Protein SCARB2.

Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) are the main causative agents of hand, foot and mouth disease (HFMD) worldwide. Studies showed that EV-A71 and CV-A16 antagonize the interferon (IFN) signaling pathway; however, how IFN controls this viral infection is largely unknown. Here, we identified an IFN-stimulated gene, Transmembrane Protein 106A (TMEM106A), encoding a protein that blocks EV-A71 and CV-A16 infection. Combined approaches measuring viral infection, gene expression, and protein interactions uncovered that TMEM106A is required for optimal IFN-mediated viral inhibition and interferes with EV-A71 binding to host cells on the receptor scavenger receptor class B member 2 (SCARB2). Our findings reveal a new mechanism contributing to the IFN-mediated defense against EV-A71 and CV-A16 infection and provide a potential strategy for HFMD treatment by using the antiviral role of TMEM106A against enterovirus.

Tooth Loss, Denture Use, and Cognitive Impairment in Chinese Older Adults: A Community Cohort Study.

BACKGROUND: Evidence regarding the associations of tooth loss and denture use with incident cognitive impairment is inconclusive in older adults, and few prospective studies have examined the potential interaction between tooth loss and denture use in these specific populations. METHODS: Data were assessed from 17 079 cognitively normal older adults aged ≥65 years, participating in the Chinese Longitudinal Healthy Longevity Survey. The outcome of interest was cognitive impairment (assessed by the Chinese version of Mini-Mental State Examination). The number of natural teeth and status of denture use were collected by a structural questionnaire. RESULTS: A total of 6456 cases of cognitive impairment were recorded during 88 627 person-years of follow-up. We found that compared with participants with 20+ teeth, those with 10-19, 1-9, and 0 teeth had increased risks of incident cognitive impairment (p-trend < .001). Participants without dentures also had a higher risk of incident cognitive impairment, compared with those who wore dentures. Effect modification by denture use was observed (p-interaction = .010). Specifically, among those without dentures, the adjusted hazard ratio (95% confidence interval) for participants with 10-19, 1-9, and 0 teeth were 1.19 (1.08, 1.30), 1.28 (1.17, 1.39), and 1.28 (1.16, 1.41), respectively, as compared to those with 20+ teeth. In contrary, among denture users, detrimental effect was only observed among those with 0 teeth (hazard ratio 1.14, 95% confidence interval: 1.16, 1.41). CONCLUSIONS: In Chinese older adults, maintaining 20+ teeth is important for cognitive health; denture use would attenuate the detrimental effects of tooth loss, especially for partial tooth loss, on cognitive impairment.

[Effects of extracellular matrix PDMS stiffness on proliferation and osteogenic differentiation of dental pulp stem cells].

PURPOSE: To investigate the effects of extracellular matrix stiffness on proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) in polydimethylsiloxane (PDMS)-based cell culture substrate model. METHODS: The premolars removed during orthodontic treatment in Changzhou NO.2 People's Hospital were collected for DPSCs culture. PDMS matrix membranes were prepared, and divided into three groups according to the different stiffness degrees, group A (binder/hardener: 10∶1; 135 kPa), group B (binder/hardener: 20∶1; 54 kPa), and group C (binder/hardener: 30∶1; 16 kPa). Group free from PDMS was set as control group. Thereafter, DPSCs cells were cultured on PDMS matrix, and various indexes were detected. The proliferation rate of DPSCs was detected by CCK-8, the osteogenic differentiation of DPSCs was detected by alizarin red staining, and the protein expression levels of osteocalcin(OCN), RUNX2, Wnt1 and ß-catenin were detected by Western blot. The data were processed with SPSS 22.0 software package. RESULTS: Alizarin red staining showed that DPSCs cells in group A had obvious morphological changes, and the cell arrangement showed obvious orientation, its morphology gradually changed from polygon and spindle shape to square shape, and calcified nodules were also observed. The number of calcified nodules among four groups were the most in the group A, followed by group B and group C, which was the lowest in control group, with significant difference (P<0.05). The cell proliferation rate and the expression of OCN, RUNX2, Wnt1 and ß-catenin were the highest in group A, followed by group B and group C, which was the lowest in control group, with significant difference(P<0.05). CONCLUSIONS: The extracellular matrix with high stiffness may promote the proliferation and osteogenic differentiation of DPSCs by activating Wnt/ß-catenin signaling pathway, which may provide a theoretical basis for periodontal tissue engineering.