Converting inorganic sulfur into degradable thermoplastics and adhesives by copolymerization with cyclic disulfides.

Converting elementary sulfur into sulfur-rich polymers provides a sustainable strategy to replace fossil-fuel-based plastics. However, the low ring strain of eight-membered rings, i.e., S8 monomers, compromises their ring-opening polymerization (ROP) due to lack of an enthalpic driving force and as a consequence, poly(sulfur) is inherently unstable. Here we report that copolymerization with cyclic disulfides, e.g., 1,2-dithiolanes, can enable a simple and energy-saving way to convert elementary sulfur into sulfur-rich thermoplastics. The key strategy is to combine two types of ROP-both mediated by disulfide bond exchange-to tackle the thermodynamic instability of poly(sulfur). Meanwhile, the readily modifiable sidechain of the cyclic disulfides provides chemical space to engineer the mechanical properties and dynamic functions over a large range, e.g., self-repairing ability and degradability. Thus, this simple and robust system is expected to be a starting point for the organic transformation of inorganic sulfur toward sulfur-rich functional and green plastics.

Dynamic Chemistry Toolbox for Advanced Sustainable Materials.

Developing dynamic chemistry for polymeric materials offers chemical solutions to solve key problems associated with current plastics. Mechanical performance and dynamic function are equally important in material design because the former determines the application scope and the latter enables chemical recycling and hence sustainability. However, it is a long-term challenge to balance the subtle trade-off between mechanical robustness and dynamic properties in a single material. The rise of dynamic chemistry, including supramolecular and dynamic covalent chemistry, provides many opportunities and versatile molecular tools for designing constitutionally dynamic materials that can adapt, repair, and recycle. Facing the growing social need for developing advanced sustainable materials without compromising properties, recent progress showing how the toolbox of dynamic chemistry can be explored to enable high-performance sustainable materials by molecular engineering strategies is discussed here. The state of the art and recent milestones are summarized and discussed, followed by an outlook toward future opportunities and challenges present in this field.

Au16 Cd16 (SC6 H11 )20 : A Glance at Structure-Property Relationship.

Doping Cd atom(s) into gold clusters is very promising in both theoretical study and practical applications. However, it has long been a challenge to synthesize heavily Cd-doped AuCd bimetallic clusters and thereby reveal their structure-property correlations. Herein a novel AuCd bimetallic cluster: Au16 Cd16 (SC6 H11 )20 (SC6 H11 denotes deprotonated cyclohexanethiol) with a Cd to Au atomic ratio of 1:1 is reported. The precise structure of the cluster determined by single crystal X-ray diffraction demonstrates that it has a unique hexatetrahedron Au14 core and a distinctive shell. Intriguingly, due to the special protecting motifs, the cluster exhibits high stability in various conditions studied, indicating that the geometric structure is crucial in determining the stability of the cluster. Most importantly, the photothermal property of the cluster has been investigated in comparison with those of M13 -kernel (M denotes metal atoms) clusters, and the results imply that the compactness and the Cd atom doping of the core play important roles in dictating the photothermal effect of the cluster. The authors believe that this work will provide some ideas for the rational design of clusters with high stability and excellent photothermal property.

Within-patient randomised clinical trial exploring the development of microskin implantation in the treatment of pressure ulcers.

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming "skin islands". The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.

A Chemically Recyclable Crosslinked Polymer Network Enabled by Orthogonal Dynamic Covalent Chemistry.

Chemical recycling of synthetic polymers offers a solution for developing sustainable plastics and materials. Here we show that two types of dynamic covalent chemistry can be orthogonalized in a solvent-free polymer network and thus enable a chemically recyclable crosslinked material. Using a simple acylhydrazine-based 1,2-dithiolane as the starting material, the disulfide-mediated reversible polymerization and acylhydrazone-based dynamic covalent crosslinking can be combined in a one-pot solvent-free reaction, resulting in mechanically robust, tough, and processable crosslinked materials. The dynamic covalent bonds in both backbones and crosslinkers endow the network with depolymerization capability under mild conditions and, importantly, virgin-quality monomers can be recovered and separated. This proof-of-concept study show opportunities to design chemically recyclable materials based on the dynamic chemistry toolbox.

Effectiveness and Efficiency of Externally Bonded CFRP Sheets for Shear Strengthening of RC Beam-Column Joints.

To develop feasible carbon fiber reinforced polymer (CFRP) retrofit schemes for the shear strengthening of real three-dimensional reinforced concrete (RC) beam-column joints, a series of parameters in relation to the contributions of the CFRP sheets externally bonded to joint panels was numerically investigated in this study. The parameters include CFRP reinforcement ratio, CFRP layout, transverse beam-to-joint panel width ratio, transverse beam-to-joint panel height ratio, location of transverse beam, and number of transverse beams. Strengthening efficiency, a new dimensionless index, was introduced to evaluate the residual effect of a CFRP-strengthening system weakened by the presence of transverse beams in comparison with the increase in joint shear capacity in relation to the one-way counterpart. The results obtained from 44 nonlinear finite element models, which were calibrated against experimental observations, confirmed the effectiveness of the CFRP strengthening technique with regard to the relatively wide ranges of the parameters. The significant differences among the roles of the parameters were revealed, and the reasons behind the differences were analyzed. Furthermore, the shear mechanism of the CFRP-retrofitted joint panels was discussed with the proposed strut-and-tie model.

Acylhydrazine-based reticular hydrogen bonds enable robust, tough, and dynamic supramolecular materials.

Supramolecular materials are widely recognized among the most promising candidates for future generations of sustainable plastics because of their dynamic functions. However, the weak noncovalent cross-links that endow dynamic properties usually trade off materials' mechanical robustness. Here, we present the discovery of a simple and robust supramolecular cross-linking strategy based on acylhydrazine units, which can hierarchically cross-link the solvent-free network of poly(disulfides) by forming unique reticular hydrogen bonds, enabling the conversion of soft into stiff dynamic material. The resulting supramolecular materials exhibit increase in stiffness exceeding two to three orders of magnitude compared to those based on the hydrogen-bonding network of analogous carboxylic acids, simultaneously preserving the repairability, malleability, and recyclability of the materials. The materials also show high adhesion strength on various surfaces while allowing multiple surface attachment cycles without fatigue, illustrating a viable approach how robustness and dynamics can be merged in future material design.

Toughening a Self-Healable Supramolecular Polymer by Ionic Cluster-Enhanced Iron-Carboxylate Complexes.

Supramolecular polymers that can heal themselves automatically usually exhibit weakness in mechanical toughness and stretchability. Here we exploit a toughening strategy for a dynamic dry supramolecular network by introducing ionic cluster-enhanced iron-carboxylate complexes. The resulting dry supramolecular network simultaneous exhibits tough mechanical strength, high stretchability, self-healing ability, and processability at room temperature. The excellent performance of these distinct supramolecular polymers is attributed to the hierarchical existence of four types of dynamic combinations in the high-density dry network, including dynamic covalent disulfide bonds, noncovalent H-bonds, iron-carboxylate complexes and ionic clustering interactions. The extremely facile preparation method of this self-healing polymer offers prospects for high-performance low-cost material among others for coatings and wearable devices.

Assembling a Natural Small Molecule into a Supramolecular Network with High Structural Order and Dynamic Functions.

Programming the hierarchical self-assembly of small molecules has been a fundamental topic of great significance in biological systems and artificial supramolecular systems. Precise and highly programmed self-assembly can produce supramolecular architectures with distinct structural features. However, it still remains a challenge how to precisely control the self-assembly pathway in a desirable way by introducing abundant structural information into a limited molecular backbone. Here we disclose a strategy that directs the hierarchical self-assembly of sodium thioctate, a small molecule of biological origin, into a highly ordered supramolecular layered network. By combining the unique dynamic covalent ring-opening-polymerization of sodium thioctate and an evaporation-induced interfacial confinement effect, we precisely direct the dynamic supramolecular self-assembly of this simple small molecule in a scheduled hierarchical pathway, resulting in a layered structure with long-range order at both macroscopic and molecular scales, which is revealed by small-angle and wide-angle X-ray scattering technologies. The resulting supramolecular layers are found to be able to bind water molecules as structural water, which works as an interlayer lubricant to modulate the material properties, such as mechanical performance, self-healing capability, and actuating function. Analogous to many reversibly self-assembled biological systems, the highly dynamic polymeric network can be degraded into monomers and reformed by a water-mediated route, exhibiting full recyclability in a facile, mild, and environmentally friendly way. This approach for assembling commercial small molecules into structurally complex materials paves the way for low-cost functional supramolecular materials based on synthetically simple procedures.

Dynamic Adaptive Two-Dimensional Supramolecular Assemblies for On-Demand Filtration.

The construction of synthetic two-dimensional (2D) materials designates a pathway to the versatile chemical functionality by spatial control. However, current 2D materials with intelligence of stimuli-responsibility and adaptiveness have been unfledged. The approach reported here uses a supramolecular strategy to achieve the dynamic non-covalent self-assembly of a rationally designed small molecule monomer, producing large-area, ultra-thin, porous 2D supramolecular assemblies, which are solution-processable in aqueous solution. Importantly, the 2D supramolecular assemblies exhibit distinct adaptive capability to automatically regulate their network density and pore diameters in response to environmental temperature change, which could be developed into an "on-demand" filtration application for nanoparticles. Meanwhile, the 2D supramolecular assemblies can also perform reversible degradation/reformation by photo-irradiation. Our results not only show the simplicity, reliability, and effectiveness of supramolecular strategies in the construction of 2D materials with practical sizes, but also push the dynamic alterability and adaptation features from supramolecular assemblies toward 2D materials.

Molybdenum sulfide Co-catalytic Fenton reaction for rapid and efficient inactivation of Escherichia coli.

As a typical advanced oxidation technology, the Fenton reaction has been employed for the disinfection, owing to the strong oxidizability of hydroxyl radicals (·OH). However, the conventional Fenton system always exhibits a low H2O2 decomposition efficiency, leading to a low production yield of ·OH, which makes the disinfection effect unsatisfactory. Herein, we develop a molybdenum sulfide (MoS2) co-catalytic Fenton reaction for rapid and highly efficient inactivation of Escherichia coli K-12 (E. coli) and Staphylococcus aureus (S. aureus). As a co-catalyst in the Fe(II)/H2O2 Fenton system, MoS2 can greatly facilitate the Fe(III)/Fe(II) cycle reaction by the exposed Mo4+ active sites, which significantly improves the H2O2 decomposition efficiency for the ·OH production. As a result, the MoS2 co-catalytic Fenton system can reach up to 83.37% of inactivation rate of E. coli just in 1 min and 100% of inactivation rate within 30 min, which increased by 2.5 times than that of the conventional Fenton reaction. Furthermore, the ·OH as the primary reactive oxygen species (ROS) in MoS2 co-catalytic Fenton reaction was measured and verified by electron paramagnetic resonance (EPR) and photoluminescence (PL). It is demonstrated an increased amount of ·OH generated from the decomposition of H2O2 in the presence of MoS2, which is responsible for the rapid and efficient inactivation of E. coli and S. aureus. This study provides a new perspective for rapid and highly efficient inactivation of bacteria in environmental remediation.

Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors.

Through a structure-based drug design approach, a tricyclic benzonaphthyridinone pharmacophore was used as a starting point for carrying out detailed medicinal structure-activity relationhip (SAR) studies geared toward characterization of a panel of proposed BTK inhibitors, including 6 (QL-X-138), 7 (BMX-IN-1) and 8 (QL47). These studies led to the discovery of the novel potent irreversible BTK inhibitor, compound 18 (CHMFL-BTK-11). Kinetic analysis of compound 18 revealed an irreversible binding efficacy (kinact/Ki) of 0.01 µM-1s-1. Compound 18 potently inhibited BTK kinase Y223 auto-phosphorylation (EC50 < 100 nM), arrested cell cycle in G0/G1 phase, and induced apoptosis in Ramos, MOLM13 and Pfeiffer cells. We believe these features would make 18 a good pharmacological tool for studying BTK-related pathologies.

Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model.

BTK plays a critical role in the B cell receptor mediated inflammatory signaling in the rheumatoid arthritis (RA). Through a rational design approach we discovered a highly selective and potent BTK kinase inhibitor (CHMFL-BTK-11) which exerted its inhibitory efficacy through a covalent bond with BTK Cys481. CHMFL-BTK-11 potently blocked the anti-IgM stimulated BCR signaling in the Ramos cell lines and isolated human primary B cells. It significantly inhibited the LPS stimulated TNF-α production in the human PBMC cells but only weakly affecting the normal PBMC cell proliferation. In the adjuvant-induced arthritis rat model, CHMFL-BTK-11 ameliorated the inflammatory response through blockage of proliferation of activated B cells, inhibition of the secretion of the inflammatory factors such as IgG1, IgG2, IgM, IL-6 and PMΦ phagocytosis, stimulation of secretion of IL-10. The high specificity of CHMFL-BTK-11 makes it a useful pharmacological tool to further detect BTK mediated signaling in the pathology of RA.

Ultradispersed Cobalt Ferrite Nanoparticles Assembled in Graphene Aerogel for Continuous Photo-Fenton Reaction and Enhanced Lithium Storage Performance.

The Photo-Fenton reaction is an advanced technology to eliminate organic pollutants in environmental chemistry. Moreover, the conversion rate of Fe(3+)/Fe(2+) and utilization rate of H2O2 are significant factors in Photo-Fenton reaction. In this work, we reported three dimensional (3D) hierarchical cobalt ferrite/graphene aerogels (CoFe2O4/GAs) composites by the in situ growing CoFe2O4 crystal seeds on the graphene oxide (GO) followed by the hydrothermal process. The resulting CoFe2O4/GAs composites demonstrated 3D hierarchical pore structure with mesopores (14~18 nm), macropores (50~125 nm), and a remarkable surface area (177.8 m(2 )g(-1)). These properties endowed this hybrid with the high and recyclable Photo-Fenton activity for methyl orange pollutant degradation. More importantly, the CoFe2O4/GAs composites can keep high Photo-Fenton activity in a wide pH. Besides, the CoFe2O4/GAs composites also exhibited excellent cyclic performance and good rate capability. The 3D framework can not only effectively prevent the volume expansion and aggregation of CoFe2O4 nanoparticles during the charge/discharge processes for Lithium-ion batteries (LIBs), but also shorten lithium ions and electron diffusion length in 3D pathways. These results indicated a broaden application prospect of 3D-graphene based hybrids in wastewater treatment and energy storage.

Simultaneous inhibition of Vps34 kinase would enhance PI3Kδ inhibitor cytotoxicity in the B-cell malignancies.

PI3Kδ has been found to be over-expressed in B-Cell-related malignancies. Despite the clinical success of the first selective PI3Kδ inhibitor, CAL-101, inhibition of PI3Kδ itself did not show too much cytotoxic efficacy against cancer cells. One possible reason is that PI3Kδ inhibition induced autophagy that protects the cells from death. Since class III PI3K isoform PIK3C3/Vps34 participates in autophagy initiation and progression, we predicted that a PI3Kδ and Vps34 dual inhibitor might improve the anti-proliferative activity observed for PI3Kδ-targeted inhibitors. We discovered a highly potent ATP-competitive PI3Kδ/Vps34 dual inhibitor, PI3KD/V-IN-01, which displayed 10-1500 fold selectivity over other PI3K isoforms and did not inhibit any other kinases in the kinome. In cells, PI3KD/V-IN-01 showed 30-300 fold selectivity between PI3Kδ and other class I PI3K isoforms. PI3KD/V-IN-01 exhibited better anti-proliferative activity against AML, CLL and Burkitt lymphoma cell lines than known selective PI3Kδ and Vps34 inhibitors. Interestingly, we observed FLT3-ITD AML cells are more sensitive to PI3KD/V-IN-01 than the FLT3 wt expressing cells. In AML cell inoculated xenograft mouse model, PI3KD/V-IN-01 exhibited dose-dependent anti-tumor growth efficacies. These results suggest that dual inhibition of PI3Kδ and Vps34 might be a useful approach to improve the PI3Kδ inhibitor's anti-tumor efficacy.

Characterization of selective and potent PI3Kδ inhibitor (PI3KDIN- 015) for B-Cell malignances.

PI3Kδ is predominately expressed in leukocytes and has been found overexpressed in B-cell related malignances such as CLL and AML. We have discovered a highly selective ATP competitive PI3Kd inhibitor PI3KD-IN-015, which exhibits a high selectivity among other PI3K isoforms in both biochemical assays and cellular assay, meanwhile did not inhibit most of other protein kinases in the kinome. PI3KD-IN-015 demonstrates moderately anti-proliferation efficacies against a variety of B-cell related cancer cell lines through down-regulate the PI3K signaling significantly. It induced both apoptosis and autophagy in B-cell malignant cell lines. In addition, combination of autophagy inhibitor Bafilomycin could potentiate the moderate anti-proliferation effect of PI3KD-IN-015. PI3KD-IN-015 shows anti-proliferation efficacy against CLL and AML patient primary cells. Collectively, these results indicate that PI3KD-IN-015 may be useful drug candidate for further development of anti-B-cell related malignances therapies.

Observation of multicellular spinning behavior of Proteus mirabilis by atomic force microscopy and multifunctional microscopy.

This study aimed to observe the multicellular spinning behavior of Proteus mirabilis by atomic force microscopy (AFM) and multifunctional microscopy in order to understand the mechanism underlying this spinning movement and its biological significance. Multifunctional microscopy with charge-coupled device (CCD) and real-time AFM showed changes in cell structure and shape of P. mirabilis during multicellular spinning movement. Specifically, the morphological characteristics of P. mirabilis, multicellular spinning dynamics, and unique movement were observed. Our findings indicate that the multicellular spinning behavior of P. mirabilis may be used to collect nutrients, perform colonization, and squeeze out competitors. The movement characteristics of P. mirabilis are vital to the organism's biological adaptability to the surrounding environment.

Effects of aluminum and extremely low frequency electromagnetic radiation on oxidative stress and memory in brain of mice.

This study was aimed to investigate the effect of aluminum and extremely low-frequency magnetic fields (ELF-MF) on oxidative stress and memory of SPF Kunming mice. Sixty male SPF Kunming mice were divided randomly into four groups: control group, ELF-MF group (2 mT, 4 h/day), load aluminum group (200 mg aluminum/kg, 0.1 ml/10 g), and ELF-MF + aluminum group (2 mT, 4 h/day, 200 mg aluminum/kg). After 8 weeks of treatment, the mice of three experiment groups (ELF-MF group, load aluminum group, and ELF-MF + aluminum group) exhibited firstly the learning memory impairment, appearing that the escaping latency to the platform was prolonged and percentage in the platform quadrant was reduced in the Morris water maze (MWM) task. Secondly are the pathologic abnormalities including neuronal cell loss and overexpression of phosphorylated tau protein in the hippocampus and cerebral cortex. On the other hand, the markers of oxidative stress were determined in mice brain and serum. The results showed a statistically significant decrease in superoxide dismutase activity and increase in the levels of malondialdehyde in the ELF-MF group (P < 0.05 or P < 0.01), load aluminum group (P < 0.01), and ELF-MF + aluminum group (P < 0.01). However, the treatment with ELF-MF + aluminum induced no more damage than ELF-MF and aluminum did, respectively. In conclusion, both aluminum and ELF-MF could impact on learning memory and pro-oxidative function in Kunming mice. However, there was no evidence of any association between ELF-MF exposure with aluminum loading.

Decreased IgA+ B cells population and IgA, IgG, IgM contents of the cecal tonsil induced by dietary high fluorine in broilers.

Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same diet supplemented with 400, 800 and 1,200 mg/kg fluorine (high fluorine groups I, II and III) in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p < 0.05 or p < 0.01) and the IgA, IgG, and IgM contents were decreased (p < 0.05 or p < 0.01) in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the 800-1,200 mg/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers.