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The direct C–H amidation or imidation of metallaaromatics with N-bromoamides or imides has been achieved under mild conditions and leads to the formation of a family of N-functionalized metallapentalyne derivatives. A unique 1,5-bromoamidated species has been identified, and can be viewed as a σH-adduct intermediate in a nucleophilic aromatic substitution. The 1,5-addition of both electrophilic and nucleophilic moieties into the metallaaromatic framework demonstrates a novel pathway in contrast to the typical radical process of arene C–H amidation involving N-haloamide reagents.

Microporous polymer membranes hold great promise in carbon capture. However, engineering a continuous CO2-selective microporous network to achieve ultrahigh gas permeance and desirable selectivity remains a grand challenge. Aiming to manipulate the pore architecture and pore chemistry to implement efficient separation, knitted microporous polymer membranes are fabricated by in situ knitting composite membranes comprised of polyphenylene oxide (PPO) polymer and benzyl alcohol (BnOH). Specifically, the crosslinkers, formaldehyde dimethylacetal, bridge the neighboring aromatic backbones of PPO chains and BnOH to construct a highly crosslinked network with microporosity. By increasing the structural bridge density, the BET surface area of membranes increases from 4 to 538 m2 g−1. The formation of a highly interconnected microporous network provides remarkably increased permeability. Meanwhile, BnOH as a hydroxyl-containing functional building unit is knitted into micropore skeletons, which can directly tune the pore size and improve the CO2-philicity for enhanced selectivity. The resulting membrane displays an ultrahigh permeability of 4651.2 barrer with a CO2/CH4 selectivity of 27, and demonstrated good resistance to plasticization (up to 30 bar) and aging (for 190 days). This knitting strategy enabling versatile combination of building units with different structures and special functionalities may set up an innovative platform for fabricating a broad range of advanced membranes.

Highly efficient and stable blue organic lighting-emitting diodes (OLEDs) continue to be a challenge. The substitution strategy has been proven to be one of the most effective chemical approaches to improve the electroluminescence (EL) performance and the operational stability of blue OLEDs based on thermally activated delay fluorescent (TADF) emitters. Herein, the effects of tert-butyl and 9-phenyl-9-fluorenyl substituents on the physicochemical properties and EL performance are systematically studied for aromatic-imide-based TADF molecules. The robust 9-phenyl-9-fluorenyl units outperform the tert-butyl groups in improving the thermal and electrochemical stability. Consequently, sky blue OLEDs based on 4-DPFCzAIAd containing 9-phenyl-9-fluorenyl substituents exhibit excellent comprehensive EL performance with a maximum external quantum efficiency of 28.2% and a long LT50 (time to 50% of initial luminance) of 178 h at an initial luminance of 500 cd m−2, which is much better than that of the device with a tert-butyl substituted emitter. These results demonstrate that the 9-phenyl-9-fluorenyl substituent is superior to the tert-butyl group in constructing TADF emitters for efficient and stable blue OLEDs.

The extent and quality, i.e. consistency, of the fusion bonding between filaments that occurs during the fused filament fabrication (FFF) process play an important role in determining the mechanical performance of 3D printed polymeric parts. This present research is designed to quantify these parameters of the fusion bonding between individual filaments deposited during the 3D printing process. Polyamide 6 (PA6) specimens were prepared from both 3D printed single-layer and single-filament films. Also, to provide a benchmark material, 3D printed PA6 films prepared by the FFF process were further processed by using compression moulding (CM) to investigate whether the fusion bonding could be enhanced. An essential work of fracture method was employed to evaluate the fusion bonding between the filaments by determining the value of the specific essential work of fracture, we, and the associated experimental reproducibility. The higher value of we, and the relatively low degree of scatter determined for the benchmark material revealed that the extent and quality of fusion bonding attained when using only the FFF process clearly needed to be improved when parts are fabricated for practical applications. To study the effect of temperature on the fusion bonding, the structural detail and fracture surfaces of thin polymer films were studied, with the thermal history of the deposited filaments also being measured using a thermal camera.

Continuous electroencephalogram (EEG) recording is vital for brain science research, monitoring pathological and physiological conditions, and the diagnosis of brain disease. Conventional wet electrodes require skin preparation and a gel electrolyte to reduce electrode–skin interface impedance (EII), which limits its further application in long-term EEG signal recording. Microneedle-array electrodes (MAEs) have been employed in EEG recording, as they can be used directly without skin preparation or the gel electrolyte. However, most microneedles used in MAE are rigid and have a high aspect ratio; thus, they can break easily. Hence, we developed a novel bendable MAE for EEG recording. It is made of a flexible polydimethylsiloxane (PDMS) pillar array with rigid microneedle tips. The PDMS pillar array could help the MAE pass through hair and enable the microneedle tips to penetrate a stratum corneum layer into a scalp, thus reducing the EII. Moreover, the PDMS pillar array is bendable, which prevents the microneedles tips from breaking. The MAE can record EEG signals well in a BIOPAC system and an Emotiv EPOC+ device. The bendable MAE may be an alternative electrode for long-term EEG recording.

Polymers of intrinsic microporosity (PIMs) exhibit high permeability but moderate selectivity, which limits their industrial application in membrane gas separations. Here, a novel CO2-philic perflu...

We report the first demonstration of a compact all-fiber visible-wavelength laser directly emitting cylindrical vector or vortex beams. The visible all-fiber cavity is constructed by a few-mode Pr/Yb-codoped ZBLAN fiber pumped by a 850 nm laser diode, a 634.6 nm few-mode fiber Bragg grating, and a visible-wavelength fiber mirror. Direct oscillation of high-order modes (LP 11 modes) at 634.6 nm wavelength is achieved using core-shifted fiber coupling method. The visible cylindrical vector beams with the radially or azimuthally polarized state can be observed. Furthermore, by adjusting the rotation of the intracavity polarization controller appropriately, two orthogonal modes (i.e., LP 11 even and LP 11 odd ) can introduce a π/2 phase difference, and the 634.6 nm vortex beams with ±1-order orbital angular momentum modes are also obtained.

Hexokinases (HXKs) have determined to be multifaceted proteins, and they are the only ones able to phosphorylate glucose in plants. However, the binding mode for ATP to plant HXKs remains unclear. Here, we report the crystal structures of rice hexokinase 6 (OsHXK6) in four different forms: (i) apo-form, (ii) binary complex with D-Glc, (iii) quaternary complex with ADP, PO4 and Mg2+, and (iv) pentanary complex with D-Glc, ADP, PO4, and Mg2+. The apo form is in the open state conformation, and the three others are in the closed state, indicating that glucose and ADP-PO4 binding induces a large conformational change by domain rearrangement. The quaternary complex is a novel intermediate during the catalytic reaction we trapped for the first time, which provides a new evidence for the enzymatic mechanism of HXKs. In addition, the latter two complexes reveal the binding mode for ADP-PO4 to plant HXKs, which provide the structural explanation for the dual-function of OsHXK6. In addition, we identified that residues Gly112, Thr261, Gly262, and Gly450 are essential to the binding between ADP-PO4 and OsHXK6 by a series of single mutations and enzymatic assays. Our study provide structural basis for the other functional studies of OsHXK6 in rice.

Covalent organic frameworks (COFs) hold great promise in molecular separations owing to their robust, ordered and tunable porous network structures. Currently, the pore size of COFs is usually much larger than most small molecules. Meanwhile, the weak interlamellar interaction between COF nanosheets impedes the preparation of defect-free membranes. Herein, we report a series of COF membranes through a mixed-dimensional assembly of 2D COF nanosheets and 1D cellulose nanofibers (CNFs). The pore size of 0.45–1.0 nm is acquired from the sheltering effect of CNFs, rendering membranes precise molecular sieving ability, besides the multiple interactions between COFs and CNFs elevate membrane stability. Accordingly, the membranes exhibit a flux of 8.53 kg m−2 h−1 with a separation factor of 3876 for n-butanol dehydration, and high permeance of 42.8 L m−2 h−1 bar−1 with a rejection of 96.8% for Na2SO4 removal. Our mixed-dimensional design may inspire the fabrication and application of COF membranes., The fabrication of defect-free covalent organic framework (COF) membranes for the separation of small molecules is challenging. Here, the authors report robust COF membranes with precise molecular sieving through a mixed-dimensional assembly, exhibiting high performance for alcohol dehydration and salt rejection.

A series of reduced lipophilic N-benzylic imidazo[1,2-a]pyridine carboxamides (IPAs) with various side chains were designed and synthesized as new anti-TB agents in this work. Five derivatives A2, A3, A4, B1 and B9 exhibit excellent in vitro activity (MIC:0.035 μM) against the drug susceptive Mycobacterium tuberculosis H37Rv strain and two clinically isolated multidrug-resistant strains, and acceptable PK properties. Compound B1 bearing a cyclohexylmethyl piperazine moiety, the same side chain of PBTZ169, was found to have obviously greater AUC

We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N-(pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, A11, C1 and C4 have not only the same excellent MIC values of 1500), opening a new direction for further development.

Covalent organic framework (COF) is an emergent class of ordered porous materials with high stability. The fabrication of thin and continuous COF membrane for small molecule separation remains challenging due to the relatively large pore size of COF materials and weak COF-substrate interfacial interaction. Herein, a two-dimensional COF layer was spin-coated on a porous substrate followed by constructing a bio-inspired calcium alginate (Alg-Ca) layer to obtain a dual-layer membrane with a thickness less than 100 nm. The Alg-Ca layer afforded a superhydrophilic surface to capture water molecules, and the porous COF layer rendered selective water channels. The dual-layer membrane synergistically strenthened the solution-diffusion mechanism through the manipulation of the membrane structure and transport process. The synergy of two layers endowed the membrane with superior water-selective performance with permeation flux of 3614 g/(m2h) and water content in permeate of 99.7 wt% for n-butanol dehydration. The fabrication of dual-layer membrane in this study may offer a new strategy for highly efficient separation of liquid small molecule mixtures.

Constructing mass transfer highways in polymer membranes via fillers with hierarchical porous and/or hollow structure is an effective approach to enhance their separation performance. In this study, novel hierarchical porous organosilica nanotubes (HPSiNT) were designed and incorporated into Pebax matrix to fabricate hybrid membranes for organic solvent separation. The HPSiNT, with plenty of micropores (∼1.6 nm) on the wall of nanotubes and atomically smooth meso-inner channels (∼6 nm), offer abundant entrances and rapid diffusion pathways for penetrant molecules, thus endowing the hybrid membranes with superior separation performance. Employing thiophene/ n -octane feed solution as a model system, the hybrid membrane that consists of 2 wt% HPSiNT exhibited a high permeation flux of 19.0 kg/(m 2 h) (increased by 66.8% compared with pure Pebax membrane) and thiophene/ n -octane enrichment factor of 5.5 (increased by 11.7% compared with pure Pebax membrane), respectively. Introducing hierarchical nano-channels in polymeric matrices could open a new avenue to designing hybrid membranes with high permeation flux.

The direct C–H amidation or imidation of metallaaromatics with N-bromoamides or imides has been achieved under mild conditions and leads to the formation of a family of N-functionalized metallapentalyne derivatives. A unique 1,5-bromoamidated species has been identified, and can be viewed as a σH-adduct intermediate in a nucleophilic aromatic substitution. The 1,5-addition of both electrophilic and nucleophilic moieties into the metallaaromatic framework demonstrates a novel pathway in contrast to the typical radical process of arene C–H amidation involving N-haloamide reagents., The direct C–H amidation of metallapentalyne has been achieved under mild conditions in which key 1,5-bromoamidated intermediates was determined.

Cytotoxic T lymphocyte (CTL), a key effector cell in aplastic anemia (AA) immune injury, is shown to be a potential target for AA drug therapy. However, there is no candidate for this target till now. Oriented by the inhibition activity of CTL and macrophage derived nitric oxide (NO), a series of novel sinomenine derivatives on rings A and C are designed, synthesized and screened. Among them, compound 3a demonstrates the best inhibitory activity on CTL with an IC50 value of 2.3 μM, and a 97.1% inhibiton rate on macrophage NO production without significant cytotoxicity. Further, compound 3a exhibits substantial therapeutic efficacy on immune-mediated BM failure in AA model mice by improving the symptoms of anemia and the function of BM hematopoiesis, and shows more advantages in life quality improving than cyclosporine A (CsA). Its efficacy on AA at least partly comes from targeting on activated cluster of differentiation (CD)8+ T cell. Additionally, 3a also shows much less toxicity (LD50 > 10.0 g/kg) than sinomenine (LD50 = 1.1 g/kg) in preliminary acute toxicity assessment in mice, and has a low risk to inhibit hERG to cause cardiotoxicity. These results indicate that compound 3a merits further investigation for AA treatment by targeting on CTL.

Inspired by the efficient facilitated diffusion via carrier proteins in biological membranes, facilitated transport membranes with synthetic carriers have been fabricated to enhance the separation performance via carrier-penetrant reversible reactions. Constructing highly ordered channels for the facilitated transport process in such membranes is favorable for achieving high efficiency, but reports are quite rare. Herein, crystalline porous covalent organic framework nanosheets (CONs) with regular pore structures, were used to load transition metal ions (typical carriers for unsaturated molecules) on their pore wall to enable a facilitated transport process in ordered channels. The physicochemical properties of the channels were elucidated by the CON microenvironments including the physical microenvironment (pore size) and the chemical microenvironment (carrier amount and carrier type). The microenvironment–performance relationship of the membranes was explored. The optimized facilitated transport membranes exhibited promising separation performance for gasoline desulfurization with a permeation flux of 21.6 kg m−2 h−1 and an enrichment factor of 6.29. Long-term operational stability and enhanced anti-swelling properties manifested superior stability of the resulting membranes.

Graphene oxide (GO) membranes display fascinating properties in molecular and ionic separation. The interlayer distance between adjacent GO nanosheets determines the separation efficiency. Currently, the interlayer distance is mostly tuned using small molecule or polymer crosslinkers, which often lead to a relatively low permeation flux due to the considerable channel occupancy. Inspired by the vein structure in nature, we propose a strategy of using vein-like supramolecular dendrimers as crosslinkers to tune the interlayer distance of GO membranes. We chose primary amine-terminated polyamidoamine (PAMAM) dendrimers with a medium molecular weight, a regularly branched structure and multiple peripheral amine groups. At a low adding amount (4 wt% PAMAM Generation 0 and equal molar of Generation 1 and 2) of dendrimers, the interlayer distance can be tuned in the range of 0.43–0.76 nm in the wet state. The resulting GO-based membranes exhibited a permeation flux of 124 kg m−2 h−1 and a NaCl rejection rate of >99.99% in simulated seawater desalination, as well as a permeation flux of 9108 g m−2 h−1 and a separation factor of 2941 in butanol dehydration, far beyond the performance of state-of-the-art membrane counterparts. Moreover, the membrane remains stable for 168 h and exhibits outstanding mechanical stability. Our study provides a novel avenue to robust and high-performance 2D nanosheet separation membranes.

Covalent organic frameworks (COFs) hold great promise in molecular separation. However, since the aperture size of most COFs is in the range of 0.8–4.9 nm, constructing COF membranes with a smaller aperture size is thus in urgent demand yet remains a grand challenge. In this study, a Bronsted acid mediated one-step self-assembly method for the fabrication of COF membranes is proposed by segregating the organic phase (containing Bronsted acids and aldehydes) from the aqueous phase (containing amines) with a polymeric support and implementing an interfacial polymerization reaction thereby. Bronsted acids, serving as a versatile mediator, can facilitate the amorphous-to-crystalline transformation, ensure the confined membrane growth at the interface and regulate the assembly behavior of COF subunits, and thus play a critical role in manipulating the microstructure evolution of COF-JLU2 membranes. More intriguingly, a correlation among membrane structures, separation performance and the partition coefficient (log P) of Bronsted acids was established. When log P lies in between 1.0 and 3.0, the COF membranes with continuous active layers, tunable thickness (50–400 nm) and small aperture size (0.49–0.51 nm) can be fabricated, achieving superior alcohol dehydration performances to all the reported membrane counterparts. Our findings may stimulate further research on bottom-up construction of COF membranes and other kinds of organic framework membranes (XOF membranes).

Hybrid membranes with 2D vertical continuous channels are expected to achieve high separation performance, but remain unexplored. In this study, 2D vertical continuous channels from layered double hydroxide (LDH) array were constructed in hybrid membranes for pervaporation dehydration. Vertically aligned LDH array that anchored onto the polyacrylonitrile substrate via in situ hydrothermal synthesis was employed to provide intrinsic continuous channels with an interlayer distance between water and ethanol. Sodium alginate impregnated into interstitial space of LDH array ensured a leakage-free and mechanical strength of membranes. The height of LDH array within hybrid membranes could be facilely manipulated from 1.5 μm to 3.6 μm through altering the hydrothermal reaction time and Co2+/Al3+ ratio. Comparing hybrid membranes with randomly oriented LDH, the hybrid membrane with vertically aligned LDH array exhibites optimal water permeability of 7742 Barrer together with a desirable selectivity of 1903 when the reaction time is 10 h, and Co2+/Al3+ ratio is 2. This study provided an innovative avenue to fabricating high-performance hybrid membranes with 2D vertical continuous channels.

Graphene oxide quantum dots (GOQDs), which inherit the monolayer of sp2 carbon atoms structure and hydrophilic groups as graphene oxide (GO) sheets, but with a quantum lateral size less than 100 nm, may hold great promise in membrane preparation. In this study, a novel nanocomposite membrane by mixing GOQDs with sodium alginate (SA) matrix was prepared for ethanol dehydration. GOQDs with an average lateral dimension around 3.9 nm provided additional shorter and less tortuous transport pathways for water molecules to penetrate the membrane compared to microsized GO sheets. Benefiting from the nanosize and high hydrophilicity of GOQDs, the nanocomposite membrane exhibited favorable ethanol dehydration performance with a total permeation flux of 2432 ± 58 g m−2 h−1, which was 60% higher than that of pristine alginate membrane, and a separation factor of 1152 ± 48. Incorporating GOQDs into the membranes can be an effective approach to improving the water permeation for water-permselective pervaporation membranes.

Molybdenum disulfide (MoS2), as an emerging kind of two-dimensional (2D) materials with large hydrophobic surface and superior mechanical property, holds great promise in preparing high-performance hybrid membranes. In this study, MoS2 nanosheets were embedded within sodium alginate (SA) for ethanol/water separation. Morphology, structure, mechanical and thermal properties of the membranes were characterized. The incorporation of MoS2 nanosheets affected the microstructure of the membranes. The Young’s modulus of the as-fabricated hybrid membrane was enhanced by 57%, and the swelling degree was reduced by 33% compared to SA pure membrane. Besides, the ordered stacking of MoS2 nanosheets, as well as their interlayer spacings, provided transport channels for water molecules. The fast transport of water molecules on the MoS2 surface is the reason that an optimum ethanol dehydration performance was achieved when the MoS2 content was 2 wt%. In ethanol/water (90/10 wt%) solution at 350 K, the permeation flux was 1839 g/(m2 h) (54% higher than that of SA/PAN pure membrane), and the separation factor was 1229 (85% greater than that of SA/PAN pure membrane). Moreover, the hybrid membrane exhibited good long-term operation stability.

[Image: see text] A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC < 0.016–0.125 μg/mL). Compound D6 displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.

Covalent organic frameworks (COFs) with well-ordered pore structures and versatile functionalities hold tremendous promise as membrane building blocks. The facile and controllable fabrication of COF membranes remains a critical challenge. Herein, we presented a one-step vapor-liquid interfacial polymerization (VLIP) method to in-situ fabricate COF membranes on substrates under mild conditions. This VLIP method features controllable COF growth at the vapor-liquid interface, acquiring COF membranes with tunable physicochemical structure. The time-dependent amorphous-to-crystalline COF growth improved the crystallinity of COF membranes, thus improving the molecular sieving property. The increased monomer concentration endowed COF membranes with higher hydrophilicity, intensifying the water sorption ability. The resultant COF membranes conferred numerous hydrophilic pathways for water-selective transport, exhibited a high and stable n-butanol dehydration performance with permeation flux of 8160 g m−2 h−1 and separation factor of 1023 over 14 days. This VLIP method may evolve into a generic platform technique to fabricate COF membranes for efficient molecular separation.

COF (covalent organic framework)-based composite membranes offer the opportunity for breakthroughs in separation performance through endowing COFs with easy film-forming properties. However, tough challenges of poor filler dispersity, limited functionality and interfacial compatibility severely restrict the development of COF-based composite membranes. Therefore, the careful design of physical and chemical structures for COFs is urgently needed. Here, a geometry transformation strategy, i.e. converting FCTF-1 (fluorinated covalent triazine frameworks) from 2D nanosheets to 0D quantum dots (QDs), is implemented to overcome some of the challenges. The greatly decreased filler size increases the solvent dispersibility and processability of FCTF-1 quantum dots (QD-FCTF-1), giving rise to thorough mixing between the polymer matrix and quantum dot filler. Apart from the changes in physical characteristics of filler, the geometry transformation using piranha solution introduces chemical functionality at the quantum dot edges, further strengthens the interfacial compatibility through the hydrogen bond interactions between polar hydroxy and amidine groups of QD-FCTF-1 and nitrile groups of PIM-1 (polymer of intrinsic microporosity). Moreover, these edge polar groups intensify favorable gas sorption due to their high affinity to CO2 molecules and thus significantly improve membrane gas pair selectivity. This work broadens the scope of framework-based materials and offers a new avenue for molecular separation.

Extraordinary mass transfer phenomenon is usually found when the small molecules pass through a confined structure, whose effective size is commensurate with the mean free path of the molecules. Small changes in the confined mass transfer structure (including size, morphology and properties) will lead to significant fluctuations of the mass transfer coefficient. The mass transfer of the penetrant molecules in the dense membranes for pervaporation, gas separation and so on, is located in the scope of confined mass transfer. Incorporating nanofillers into polymer matrix to construct mixed matrix membranes (MMMs) is an effective approach to tune the confined mass transfer structure and enhance the performance of the widely used polymeric membranes. This review focuses on the construction and manipulation of the confined structure in the polymeric membranes via incorporating one-dimensional (1D), two-dimensional (2D) and three-dimensional (3D) fillers. The comparison of the MMMs for pervaporation is summarized, and the research prospective of the MMMs is provided.

Hepatocellular carcinoma (HCC) results in large amounts of deaths each year worldwide. To develop more effective treatments for HCC, it is very necessary to define the molecular mechanisms in hepatocarcinogenesis. Mixed lineage kinase (MLK)-4 is a member of the MLK family of mitogen-activated protein kinase kinase kinases, and modulates different cellular responses. However, its role in the meditation of HCC progression remains unclear. In the study, we found that MLK4 was over-expressed in tumor samples of HCC patients. High MLK4 expression was significantly associated with shorter overall survival in HCC. Knockdown of MLK4 inhibited HCC cell proliferation and metastasis, which was partly through reducing matrix metalloproteinase (MMP)-13, MMP2, enhancer of zeste homolog 2 (EZH2) and Vimentin expressions. Apoptosis was significantly induced by MLK4 knockdown in HCC cells via decreasing Bcl-2 and increasing cleaved poly (ADP-ribose) polymerase (PARP), Caspase-7 and -3 expression levels. In addition, MLK4 silence led to a significant reactive oxygen species (ROS) production in liver cancer cells, accompanied with elevated expression of phosphorylated p38, c-Jun N-terminal kinase (JNK) and ERK1/2. Notably, reducing ROS generation and blocking MAPKs (p38/JNK/ERK1/2) signaling markedly abrogated MLK4 knockdown-induced apoptosis in HCC cells. Moreover, MLK4 silence-prevented metastasis was also rescued by scavenging ROS generation and repressing MAPKs pathway. In vivo, injection of MLK4 siRNA markedly inhibited liver tumor growth in xenograft models, and MLK4 knockdown reduced HCC lung metastasis. Together, our study indicated the essential function of MLK4 in HCC progression, providing crucial therapeutic hypothesis for the prevention of hepatocellular carcinoma.

IMB1603, a new benzothiazinone lead discovered by our lab, exhibited potent anti-MTB activity in vitro and in vivo, but significant hERG binding potency (IR 90% at 10 μM). Thus, we embarked on a lead optimization program with the goal of identifying alternative leads that could reduce the hERG liability without sacrificing antimycobacterial potency. Compounds 2c and 4c were identified to maintain the anti-MTB activity (MICs0.035-0.078 μM), and had lower hERG binding affinity (IR 50% at 10 μM). Both of them were also found to have acceptable safety and pharmacokinetic properties. Studies to determine the in vivo efficacy of 2c and 4c are currently underway.

Covalent organic frameworks (COFs) have gained tremendous interest as membrane building blocks owing to rigid, long-range ordered and easily functionalized skeletons. The facile, controllable and task-specific construction of COF membranes lies in the frontier of membrane technology. Herein, we explored a post-synthetic linker exchange (PLE) method to engineer COF membranes for efficient alcohol dehydration. The proposed PLE method, utilizing the reversible breaking-reformation basis between pristine COF membranes and post-introduced linkers, narrowed the effective pore size to intensify molecular sieving property. Moreover, the PLE method also endowed COF membranes with more hydrophilic groups, thus improving the water sorption ability of COF membranes. The resultant COF membranes exhibited superior n-butanol dehydration performances with 3620 of selectivity, 11.35 kg m−2 h−1 of total flux and remained stable in 15-day operation. This PLE method may flourish the library of engineering COF membranes for efficient molecular separations.

Two-dimensional (2D) materials have exhibited tremendous potential as functional fillers of hybrid membranes. Manipulating the orientation of 2D fillers in hybrid membranes, a decisive factor in determining the separation performance, proves a critical challenge. In this study, hybrid membranes with vertical superparamagnetic Fe3O4 nanoflakes and sodium alginate (SA) matrix were prepared via the external magnetic field. The vertically aligned Fe3O4 nanoflakes constructed highly efficient interfacial regions for penetrants transport in hybrid membranes, which shortened the molecular diffusion pathways. In addition, the orientated fillers increased surface hydrophilicity of the hybrid membranes by enhancing the surface roughness. The effect of Fe3O4 nanoflakes orientation and content in hybrid membranes on the separation performance was systematically investigated. When the filler content is 0.4 wt%, the hybrid membrane with vertically aligned Fe3O4 nanoflakes achieved superior ethanol dehydration performance with an optimized selectivity of 3248 ± 233 and a decent water permeability of 1436 ± 169 Barrer, which increased by 68% and 133% compared to the hybrid membranes with horizontally aligned Fe3O4 nanoflakes, respectively. This strategy of manipulating 2D filler orientation may render hybrid membranes with more possibilities for enhanced separation performances.

This study examines the effect of striker shape on the energy absorption of a shear thickening fluid (STF) with 58.8 vol% styrene/acrylate co-polymer particles in ethylene glycol (EG). Low-velocity impact tests were performed on the STF with six different strikers: three cone-shaped strikers and three flat-head strikers with different diameters. Higher total impact energy absorption was recorded for the flat-head strikers, yet lower maximum penetration depth than the cone-shaped strikers of the same diameter. The total impact energy absorption also increased when the striker diameter increased, but with lower penetration depth.

The production of continuous carbon fibre composites using a fused deposition modelling (FDM) method has addressed the problem of low mechanical performance of raw- or short-fibre reinforced polymer parts fabricated by the same process, due to the excellent specific strength and stiffness of continuous fibres. However, one key issue of 3D printed polymers or fibre-reinforced polymers is the formation of microscopic voids between individual filaments and within the filaments during the FDM process. This study aims to quantify the adverse effects of voids on 3D printed continuous fibre-reinforced polymer composites. Optical microscopy and micro-CT are used to quantify the void content in continuous CF/PA6 composites fabricated on a 3D printing platform. As a benchmark, 3D printed CF/PA6 composites with the same printing configurations were further processed by compression moulding (CM) with thickness controlled to achieve the minimum void content. Apart from tensile and three-point bending tests in the longitudinal and transverse directions, the study also evaluated the Mode I interlaminar fracture toughness of CF/PA6 composites. By revealing the substantial adverse effects of the microscopic voids in 3D printed composites, this study articulates the critical importance of developing in-process techniques during 3D printing to decrease the void content within the continuous fibre reinforced composites, for the sake of expanding practical applications of 3D printed continuous fibre composites.

2D material membranes with well-defined interlayer nanochannels hold great promise for precise molecular separation, where the size and surface chemical property of the channel determine the separation efficiency. The currently reported 2D material membranes for efficient CO2 separation are primarily built by introducing crosslinkers or intercalators into the interlayer channel. In this study, we demonstrate a novel 2D material membrane with inherent CO2-selective transport channels based on layered double hydroxide (LDH). The intrinsic breathing effect of LDH toward CO2 enables the spontaneous incorporation of CO2 molecules into the interlayer nanochannels and subsequent conversion/transport in the form of CO32− species which are released as CO2 at the downstream side of membrane. Moreover, the intercalated CO32− ions with an ionic radius of 0.136 nm narrow down the nanochannel size from 0.7 nm to 0.3 nm by electrostatic interaction with LDH layers, conferring the membrane a distinct molecular sieving ability for CO2/CH4 separation. The unique breathing effect and size-sieving effect jointly contribute to the high membrane separation performance with CO2 permeance of 150 GPU and CO2/CH4 selectivity of 33. This study is anticipated to extend the materials and strategies for design of the CO2 preferential transport channels in membranes.

The interlayer distance of stacked graphene oxide (GO) membranes is the decisive factor of achieving high permeability and selectivity. Fixating the size of 2D channel in GO membrane proves a critical challenge for liquid separation. Herein, GO membrane was firstly crosslinked by polyvinylamine (PVAm) to acquire mechanically stable membrane, and PVAm then induced the biomimetic mineralization to in situ generate silica as the second crosslinker to further fixate the size of 2D channels. The interlayer distance of GO-PVAm-Silica membrane fixed around 0.62 nm in water, showing the improved swelling resistance compared to the GO-PVAm membrane. The resultant GO-PVAm-Silica membrane featured high water permeability as well as distinct sieving properties for bio-alcohol molecules and hydrated ions. To be specific, the membrane exhibited a superior pervaporative dehydration performance with separation factor of 1188 ± 39 and flux of 12.9 ± 0.3 kg/(m2h) under 80 °C for 90 wt% butanol/water mixture. And the membrane showed a high NaCl rejection rate of higher than 99.99% and total permeation flux of 80.2 ± 0.8 kg/(m2h) when treating 3.5 wt% NaCl solution under 70 °C. Moreover, the GO-PVAm-Silica membrane kept excellent operation stability in 168 h test.

We report herein the design and synthesis of a series of less lipophilic Q203 derivatives containing an alkaline fused ring moiety. Most of them show considerable potency against MTB H37Rv strain (MIC 0.25 μM). Nine compounds (13, 15, 19, 21, 23, 25, 29, 35, 36) have the same excellent activity against both drug-sensitive and -resistant strains (MIC 0.035 μM) as Q203 and PBTZ169. Especially, compound 29 also displays acceptable safety, greater absorption in plasma and aqueous solubility than Q203, suggesting its promising potential to be lead compound for future antitubercular drug discovery.

Aim: Tuberculosis (TB) is one of the world's deadliest chronic infectious diseases caused mainly by Mycobacterium tuberculosis (MTB). Many nitrofuran derivatives were found to possess promising anti-TB potential and have been widely studied. In our previous study, we discovered diazaspiro-nitrofuran IMB1701-1702 as potent anti-TB agents. Methodology: We report herein a series of nitrofuranyl methyl N-heterocycles based on IMB1701-1702. Results reveal that most of them show potent activity (minimum inhibitory concentration

A solid oxide fuel cell (SOFC) with a liquid antimony anode is fabricated based on a smooth single crystal YSZ electrolyte substrate and a porous Pt cathode. The performance of the liquid antimony anode was tested under “battery mode”, with the anode chamber shielded in argon throughout the test and the cathode exposed to air. Polarization curves were taken and a long term constant potential discharging test was carried out afterwards. Taking electrochemical reaction, mass transport and microstructure of the liquid Sb anode into consideration, a one dimensional mathematical model was built and then validated by the polarization curve and the constant potential discharging performance curve obtained during the test. This model analyzes the metallic Sb distribution in the anode during cell operation, explains the cell performance evolution base on the microstructural development of the liquid Sb anode and simulates how the anode microstructure affects the cell performance.

We report the first demonstration of a miniaturized mid-infrared all-fiber laser operating at 2.9 $\mu\text{m}$ . The linear laser cavity consists of a 55 cm Ho3+:zblan fiber, a home-made 1154 nm Raman fiber laser as pump source, and a fiber end-faced mirror as input mirror. Stable lasing at 2865 nm was achieved with the maximum output power of 67 mW and a slope efficiency of~48.9%.

Phytate is an important antinutritional factor in food products. In this study, a phytase-assisted processing method was used to produce low-phytate soybean protein isolate (SPI) samples, and their physicochemical and functional properties were examined. Hydrolysis condition at low temperature (room temperature) and pH 5.0 was better than that recommended by manufacturer (pH 5.0, 55 °C) at keeping the properties of SPI, so the former condition was selected to prepare SPI samples with phytate contents of 19.86-0.11 mg/g by prolonging hydrolysis time (0 (traditional method), 5, 10, 20, 40, and 60 min). Ash content (R(2) = 0.940), solubility (R(2) = 0.983), ζ-potential value (R(2) = 0.793), denaturation temperatures (β-conglycinin, R(2) = 0.941; glycinin, R(2) = 0.977), emulsifying activity index (R(2) = 0.983), foaming capacity (R(2) = 0.955), and trypsin inhibitor activity (R(2) = 0.821) of SPI were positively correlated with phytate content, whereas protein content (R(2) = 0.876), protein recovery (R(2) = 0.781), emulsifying stability index (R(2) = 0.953), foaming stability (R(2) = 0.919), gel hardness (R(2) = 0.893), and in vitro digestibility (R(2) = 0.969) were negatively correlated with phytate content. Simulated gastrointestinal digestion and subsequent dialysis showed that percentages of dialyzable Zn and Ca were increased with decreasing phytate content, whereas the amounts of dialyzable Zn and Ca revealed different behaviors: the former was increased and the latter was decreased. Circular dichroism spectra showed that secondary structure of SPI was changed by phytase. Compared with traditional processing method, the phytase-assisted processing method could produce SPI with lower phytate and higher protein contents, which had better in vitro digestibility and could be used to prepare gels with higher hardness by partially losing some other functional properties.

A direct carbon solid oxide fuel cell (DC-SOFC) with liquid metallic antimony (Sb) anode was assembled. This type of DC-SOFC provides a new way to utilize coal in a both efficient and clean way. The intrinsic reaction kinetics of the liquid Sb anode was closely observed and analyzed without the presence of fuel, and a promotion of cell performance derived from cell discharging was discovered. Then the de-ash coal (ash 2.56 wt%) was added in as the fuel, which made the performance of the fuel cell rise dramatically. The interaction between the coal and the Sb based anode under different working temperature was studied, and a conclusion of direct oxidation of carbon at electrolyte-anode interface is drawn from the experimental data. A novel concept of liquid mixed conducting networks is proposed as a reaction mechanism in the anode region for the first time, which involves the interaction among Sb, Sb 2 O 3 (antimony oxide) and coal, perfectly explained the phenomenon observed in the experiment.

When capillary flow occurs in a uniform porous medium, the depth of penetration is known to increase as the square root of time. However, we demonstrate in this study that the depth of penetration in multi-section porous layers with variation in width and height against the flow time is modified from this diffusive-like response, and liquids can pass through porous systems more readily in one direction than the other. We show here in a model and an experiment that the flow time for a negative gradient of cross-sectional widths is smaller than that for a positive gradient at the given total height of porous layers. The effect of width and height of local layers on capillary flow is quantitatively analyzed, and optimal parameters are obtained to facilitate the fastest flow.

We report, to the best of our knowledge, the first demonstration of a wavelength-tunable and highly efficient Dy3+-doped fiber laser operating in the yellow spectral region. A 2-m-long Dy3+:ZBLAN fiber pumped by a 447-nm GaN laser diode provides a strong down-conversion gain around 575 nm. A fiber end-facet mirror and a visible reflective grating in the Littrow configuration construct the resonant cavity and introduce the wavelength tunability. A stable yellow laser with a

The feasibility of inkjet printing of electrodes for direct carbon solid oxide fuel cells (DC-SOFC) was tested. A variety of materials was deposited by direct ceramic inkjet printing (DCIJP). The technology allows for easy modification of the coatings, including thickness control, porosity graduation and precise infiltration with catalytically active materials. The comparative tests showed a similar performance for screen printed and inkjet printed cells (peak power density of ca. 80 mW cm-2 at 780°C). In addition DCIJP offers minimization of the usage of expensive precursor materials. It was also found that infiltration of the anode by inkjet printing of sol inks (CuNiO3) can lead to an improvement in DC-SOFC performance. © The Electrochemical Society.

H2O–CO2 electrochemical conversion in solid oxide electrolysis cells (SOECs) is one of the efficient ways to reduce CO2 emission and to simultaneously store the renewable power. In this study, H2O–CO2 co-electrolysis performance and mechanisms in solid oxide electrolysis button cells at different operating temperature (550–750 °C) is tested. The results indicated that the co-electrolysis performance for Ni-YSZ/ScSZ/LSM-ScSZ electrolysis cell increases significantly with temperature. The mass transfer gradually became the rate-determining step of the whole electrodes process below 750 °C. By substituting half of the carrier gas to CO2 for the H2O electrolysis system, the electrochemical performance of SOEC became worse, lied between that of H2O and CO2 electrolysis, and was slightly closer to H2O electrolysis at 750 °C. CH4 is only detected in the gas products from the reactant composition of 28.6%H2O + 14.3%CO2 + 57.1%Ar, when the operating voltage of the electrolysis cell is higher than 2 V. The CH4 production can be significantly promoted by electricity and can be effectively suppressed by impregnating the anti-carbon deposition catalyst Ru in porous Ni-YSZ cathode. The reactions between carbon element on the electrode surface and hydrogen C(s) + 2H2 → CH4 is proposed as one of reaction pathways for CH4 production in H2O–CO2 high temperature co-electrolysis process.