Construction of a human cell landscape at single-cell level.

Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems1. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a 'single-cell HCL analysis' pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.

Photostimulated Covalent Linkage Transformation Isomerizing Covalent Organic Frameworks for Improved Photocatalytic Performances.

Covalent organic frameworks (COFs) offer a desirable platform to explore multichoromophoric arrays for photocatalytic conversion. Symmetric arrangement of choromophoric modules over π-extended frameworks enhances exciton delocalization while impairing excitation density and accordingly photochemical reactivity. Herein, a photoisomerization-driven strategy is proposed to break the excited-state symmetry of ketoenamine-linked COFs with multichoromophoric arrays. Incorporating electron-withdrawing benzothiadiazole facilitates the ultrafast excited-state intramolecular proton transfer (ESIPT) from enamine to keto within 140 fs, resulting in partially enolized COF isomers. The hybrid linkages containing imine and enamine bonds at the node of framework alter the symmetry of electronic structure and enforce the photoinduced charge separation. Increasing the imine-to-enamine ratio further promotes the electron transferred number in a long range, thereby affording the optimum photocatalytic hydrogen evolution rate. This work put forward an ESIPT-induced photoisomerization to build a symmetry-breaking COF with weakened exciton effect and enhanced photochemical reactivity.

A Phosphine-Amine-Linked Covalent Organic Framework with Staggered Stacking Structure for Lithium-Ion Conduction.

In-plane ionic conduction over two-dimensional (2D) materials is desirable for flexible electronics. Exfoliating 2D covalent organic frameworks (COFs) towards a few layers is highly anticipated, whereas most examples remain robust via π-stacking against the interlayered dislocation. Herein, we synthesize a phosphine-amine-linked 2D COF by a nucleophilic substitution reaction of phosphazene with amines. The synthesized COF is crystalline, and stacks in an AB-staggered fashion, wherein the AB dual layers are interlocked by embedding P-Cl bonds from one to another layer, and the non-interlocked layers are readily delaminated. Therefore, in situ post-quaternization over phosphazene can improve the ionization of backbones, accompanied by layered exfoliation. The ultrathin nanosheets can decouple lithium salts for fast solid-state ion transport, achieving a high conductivity and low activation energy. Our findings explore the P-N substitution reaction for COF crystallization and demonstrate that the staggered stacking 2D COFs are readily exfoliated for designing solid electrolytes.

Multivariate Synthetic Strategy for Improving Crystallinity of Zwitterionic Squaraine-Linked Covalent Organic Frameworks with Enhanced Photothermal Performance.

Two-dimensional covalent organic frameworks (2D COFs) offer a designable platform to explore porous polyelectrolyte frameworks with periodic ionic skeletons and uniform pore channels. However, the crystallinity of ionized 2D COF is often far from satisfactory as the electrostatic assembly of structures impedes the ordered layered arrangement. Here, a multivariate synthetic strategy to synthesize a highly crystalline squaraine (SQ)-linked zwitterionic 2D COF is proved. A neutral aldehyde monomer copolymerizes with squaric acid (SA) and amines in a controlled manner, resulting in the ionized COF with linkage heterogeneity in one tetragonal framework. Thus, the zwitterions of SQ are spatially isolated to minimize the electrostatic interaction and maintain the highly ordered layered stacking. With the addition of 85%-90% SA (relative to a total of aldehydes and SA), a fully SQ-linked zwitterionic 2D COF is achieved by the in-situ conversion of imine to SQ linkages. Such a highly crystalline SQ-linked COF promotes absorptivity in a full spectrum and photothermal conversion performances, and in turn, it exhibits enhanced solar-to-vapor generation with an efficiency of as high as 92.19%. These results suggest that synthetically regulating charge distribution is desirable to constitute a family of new crystalline polyelectrolyte frameworks.

Proton/Electron Donors Enhancing Electrocatalytic Activity of Supported Conjugated Microporous Polymers for CO2 Reduction.

Metal phthalocyanines (MePc) hold great promise in electrochemical reduction of CO2 to value-added chemicals, whereas the catalytic activity of MePc-containing polymers often suffers from a limited molecular modulation strategy. Herein, we synthesize an ultrathin conjugated microporous polymer sheath around carbon nanotubes by an ionothermal copolymerization of CoPc and H2 Pc via the Scholl reaction. Given the H2 Pc-mediated regulation in the synthesis, CoII metal is well preserved in the form of single atoms on the polymer sheath of the carbon nanotubes. With the synergistic effect of H2 Pc moieties as proton/electron donors, the composites can selectively reduce CO2 to CO with a high Faradaic efficiency (max. 97 % at -0.9 V) in broad potential windows, exceptional turnover frequency (97 592 h-1 at -0.65 V) and large current density (>200 mA cm-2 ). It is thus desirable to develop a family of heterogeneous polymerized MePc with molecularly regulating electrocatalytic activity.

MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC.

BACKGROUND: The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as "self", evade the surveillance of the immune system, and accumulate to the tumor sites actively. RESULTS: Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate-an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. CONCLUSIONS: These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

Covalent Organic Frameworks Enabling Site Isolation of Viologen-Derived Electron-Transfer Mediators for Stable Photocatalytic Hydrogen Evolution.

Electron transfer is the rate-limiting step in photocatalytic water splitting. Viologen and its derivatives are able to act as electron-transfer mediators (ETMs) to facilitate the rapid electron transfer from photosensitizers to active sites. Nevertheless, the electron-transfer ability often suffers from the formation of a stable dipole structure through the coupling between cationic-radical-containing viologen-derived ETMs, by which the electron-transfer process becomes restricted. Herein, cyclic diquats, a kind of viologen-derived ETM, are integrated into a 2,2'-bipyridine-based covalent organic framework (COF) through a post-quaternization reaction. The content and distribution of embedded diquat-ETMs are elaborately controlled, leading to the favorable site-isolated arrangement. The resulting materials integrate the photosensitizing units and ETMs into one system, exhibiting the enhanced hydrogen evolution rate (34600 µmol h-1 g-1 ) and sustained performances when compared to a single-module COF and a COF/ETM mixture. The integration strategy applied in a 2D COF platform promotes the consecutive electron transfer in photochemical processes through the multi-component cooperation.

Stable Radical Cation-Containing Covalent Organic Frameworks Exhibiting Remarkable Structure-Enhanced Photothermal Conversion.

The production of a radical cation-containing covalent organic framework (COF) has been accomplished by sequential in situ reactions, quaternization, and one-electron reduction of the 2,2'-bipyridine-based COFs. The acid-catalyzed COF formation enables the cis configuration of 2,2'-bipyridyl moieties in the structure, of which the stability arises from the eclipsed stacking of the two-dimensional layered structure. The postfunctionalization generates cyclic alkylated diquats as the sole products from the controlled quaternization. The reduction of diquat cations on the COF skeletons results in a large number of radical cations, which delocalize and uniaxially stack on top of one another by virtue of interlayered π-electronic couplings. The absorption of the near-infrared (NIR) region exhibited by the cationic radical COF is remarkably high owing to the intercharge transfer across the π-coupling interlayers. Also, the long-range array of extended and planar frameworks in such a COF leads to the extra stability of the radical cations against external stresses. The structure-enhanced performance of the COF material is witnessed with photothermal conversion efficiencies of as high as 63.8 and 55.2% when exposed to 808 and 1064 nm lasers, respectively. Further PEG modification on such a COF allows photoacoustic imaging and photothermal therapy in vivo under NIR light illumination to be manifested.

Specific Hypersensitive Response-Associated Recognition of New Apoplastic Effectors from Cladosporium fulvum in Wild Tomato.

Tomato leaf mold disease is caused by the biotrophic fungus Cladosporium fulvum. During infection, C. fulvum produces extracellular small secreted protein (SSP) effectors that function to promote colonization of the leaf apoplast. Resistance to the disease is governed by Cf immune receptor genes that encode receptor-like proteins (RLPs). These RLPs recognize specific SSP effectors to initiate a hypersensitive response (HR) that renders the pathogen avirulent. C. fulvum strains capable of overcoming one or more of all cloned Cf genes have now emerged. To combat these strains, new Cf genes are required. An effectoromics approach was employed to identify wild tomato accessions carrying new Cf genes. Proteomics and transcriptome sequencing were first used to identify 70 apoplastic in planta-induced C. fulvum SSPs. Based on sequence homology, 61 of these SSPs were novel or lacked known functional domains. Seven, however, had predicted structural homology to antimicrobial proteins, suggesting a possible role in mediating antagonistic microbe-microbe interactions in planta. Wild tomato accessions were then screened for HR-associated recognition of 41 SSPs, using the Potato virus X-based transient expression system. Nine SSPs were recognized by one or more accessions, suggesting that these plants carry new Cf genes available for incorporation into cultivated tomato.

Ultradeep Palmitoylomics Enabled by Dithiodipyridine-Functionalized Magnetic Nanoparticles.

Palmitoylation, a type of fatty acylation, has vital roles in many biological processes. For ultradeep identification of protein palmitoylation, an enrichment approach based on a novel magnetic microsphere modified with 2,2'-dithiodipyridine (Fe3O4/SiO2-SSPy microsphere) is presented in this study. The Fe3O4/SiO2-SSPy microspheres were synthesized by directly coating thiol-containing silane coupling agent onto the magnetic supraparticles in aqueous solution at room temperature. Due to the intrinsic magnetic properties, high surface-to-volume ratios, and abundant reactive functional groups on the surface, these microspheres enabled direct capture of palmitoylated targets and convenient isolation, contributing to remarkable enrichment selectivity (purifying palmitoylated peptides from mixtures with nonpalmitoylated peptides even at a 1:500 molar ratio) and sensitivity (the detection limit was at femtomole level), thus enabling a global annotation of protein palmitoylation for complex biological samples. We successfully identified 1304 putative palmitoylated proteins from mouse brain tissues by using this method, which is the largest mouse palmitoylome data set to date. Except for those known members, many new proteins and pathways were also found to be regulated by palmitoylation.

Structure stabilization effect of configuration entropy in cubic WN.

The microscopic structure of cubic WN has been studied combining scanning transmission electron microscopy and first-principles calculations. Because of the contribution of configurational entropy, NaCl-type WN with disordered vacancies becomes more stable at high temperatures than NbO-type WN. Moreover, electron beam irradiation can induce an order-disorder transition in cubic WN. It is suggested that the ordered NbO-type WN can be obtained after annealing below the transition temperature. The results shed light on the stability of materials synthesized at high pressures and high temperatures.

Morphology-Controlled Coating of Colloidal Particles with Silica: Influence of Particle Surface Functionalization.

We present a general, convenient, and efficient synthetic concept for the coating of colloidal particles with a silica (SiO2) shell of well-defined and precisely controlled morphology and porosity. Monodisperse submicroscopic polystyrene (PS) particles were synthesized via two-stage emulsifier-free emulsion polymerization and subsequent swelling polymerization, enabling selective particle surface modification by the incorporation of ionic (methacrylic acid, MAA) or nonionic (hydroxyethyl methacrylate, HEMA or methacrylamide, MAAm) comonomers, which could be proven by zeta potential measurements as well as by determining the three-phase contact angle of the colloidal particles adsorbed at the air-water and n-decane-water interface. The functionalized particles could be directly coated with silica shells of variable thickness, porosity, and controlled surface roughness in a seeded sol-gel process from tetraethoxysilane (TEOS), leading to hybrid PS@silica particles with morphologies ranging from core-shell (CS) to raspberry-type architectures. The experimental results demonstrated that the silica coating could be precisely tailored by the type of surface functionalization, which strongly influences the surface properties of the colloidal particles and thus the morphology of the final silica shell. Furthermore, the PS cores could be easily removed by thermal treatment, yielding extremely uniform hollow silica particles, while maintaining their initial shell architecture. These particles are highly stable against irreversible aggregation and could be readily dried, purified, and redispersed in various solvents. Herein we show a first example of coating semiconducting CdSe/ZnS nanocrystals with smooth and spherical silica shells by applying the presented method that are expected to be suitable systems for applications as markers in biology and life science by using fluorescence microscopy methods, which are also briefly discussed.

Role of Protecting Groups in Synthesis and Self-Assembly of Glycopolymers.

Protection and deprotection are basic procedures in oligosaccharide synthesis. By taking advantage of the processes of attaching and removing the protecting groups, preparation of oligosaccharides with complex structures can be achieved with relatively high yields. However, the role of protecting groups in solution properties and self-assembly of synthetic glycopolymers has been overlooked in the literature. In this paper, we focused on such effects for well-designed copolymers in which different numbers of benzyl (Bn) groups are installed regioselectively in saccharide rings. Thus, three block copolymers P1, P2, and P3 composed of a common block of PNIPAm and a glycopolymer block with trisaccharide triMan side chains differing in the respective number of Bn (0, 2, and 6) were prepared. The solutions of these block copolymers in water were investigated by dynamic and static light scatting and VT-1H NMR. We found that all of the three copolymers P1, P2, and P3 formed association at room temperature. Particularly, P1 associated loosely due to carbohydrate-carbohydrate interaction (CCI) while P3 formed tight aggregates due to hydrophobic interactions between Bn, and P2 behaved between those of P1 and P3. Moreover, upon heating, phase transition of PNIPAm block took place leading to micelle formation. Hydrodynamic radius of P1 and P2 increased significantly as expected, while P3 did not follow this trend, because during heating, collapse and accumulation of the PNIPAm chains would occur within the tight aggregates mainly, so it leads to a little change of the size.

Synthesis and Mechanical Character of Hexagonal Phase δ-WN.

In this work, high-quality bulk WC-structured WN (δ-WN) was synthesized via an untraditional method and the structure was accurately determined by X-ray diffraction and Rietveld refinement. In the process of synthesizing δ-WN, W2N3 and melamine were used as tungsten source and nitrogen source, respectively. The result of successfully synthesized high-quality δ-WN indicates that our method is an effective route for synthesizing high-quality bulk δ-WN and melamine is a pure nitrogen source for introducing the nitrogen to the metal precursor. The mechanical properties, bulk modulus, and Vickers hardness (HV) were first investigated by in situ high-pressure X-ray diffraction and Vickers microhardness tests, respectively. It is worth noting that the bulk modulus of δ-WN is 373 ± 8.3 GPa, which is comparable to that of c-BN. The Vickers hardness is 13.8 GPa under an applied load of 4.9 N. It is worth noting that W-W metallic bond and W-N ionic bond are mainly chemical bond in δ-WN based on the analysis of electron localization function (ELF), density of states (DOS), and Mulliken population. This result can well clarify that δ-WN is only a hard material for the lack of strong W-N covalent bonds to form 3D network structure. Our results are helpful to understand the hardness mechanism and design superhard materials in transition-metal nitrides.

WB2: not a superhard material for strong polarization character of interlayer W-B bonding.

In this work, the structure of WB2 synthesized at high pressure and high temperature (HPHT) was accurately determined by X-ray diffraction and Rietveld refinement. Its asymptotic Vickers hardness (Hv) value is 25.5 GPa which is much lower than the previous theoretical results (36-40 GPa). It is worth noting that the chemical bonds between the W layers and two different kinds of B layers show obvious polarization character based on the results obtained from X-ray photoelectron spectroscopy (XPS) and electron localization functions (ELFs), density of states (DOS), topological analysis of the static electron density and Mulliken population. This result can well clarify that WB2 is only a hard but not superhard material. Thus, a 3D network structure can not be formed between the W layers and the B layers which is previously predicted by theoretical calculations. Our results are helpful to understand the hardness mechanism and design superhard materials in TMBs.

Magnetic Nano-Sponges for High-Capacity Protein Enrichment and Immobilization.

On the basis of the gel effect of the living RAFT (Reversible Addition-Fragmentation Chain Transfer) polymerization, magnetic nano-sponges with ultrasoft PAA net-like shells are prepared and then used for enriching the entire proteins from real biological samples with ultrahigh capacity. In addition, the immobilized enzyme Cyt c or HRP surprisingly show much higher catalytic activity than free enzymes.

Biodegradable Smart Nanogels: A New Platform for Targeting Drug Delivery and Biomedical Diagnostics.

Nanogels (or nanohydrogels) have been extensively investigated as one of the most promising nanoparticulate biomedical platforms owing to their advantageous properties that combine the characteristics of hydrogel systems with nanoparticles. Among them, smart nanogels that have the ability to respond to external stimuli, such as pH, redox, temperature, enzymes, light, magnetic field and so forth, are most attractive in the area of drug delivery. Besides, numerous multifunctionalized nanogels with high sensitivity and specificity were designed for diagnostic applications. In this feature article, we have reviewed and discussed the recent progress of biodegradable nanogels as smart nanocarriers of anticancer drugs and biomedical diagnostic agents for cancer.

Enzymatic Activities of Polycatalytic Complexes with Nonprocessive Cellulases Immobilized on the Surface of Magnetic Nanoparticles.

Polycatalytic enzyme complexes made by immobilization of industrial enzymes on polymer- or nanoparticle-based scaffolds are technologically attractive due to their recyclability and their improved substrate binding and catalytic activities. Herein, we report the synthesis of polycatalytic complexes by the immobilization of nonprocessive cellulases on the surface of colloidal polymers with a magnetic nanoparticle core and the study of their binding and catalytic activities. These polycatalytic cellulase complexes have increased binding affinity for the substrate. But due to their larger size, these complexes were unable to access to the internal surfaces of cellulose and have significantly lower binding capacity when compared to those of the corresponding free enzymes. Analysis of released soluble sugars indicated that the formation of complexes may promote the prospect of having consistent, multiple attacks on cellulose substrate. Once bound to the substrate, polycatalytic complexes tend to remain on the surface with very limited mobility due to their strong, multivalent binding to cellulose. Hence, the overall performance of polycatalytic complexes is limited by its substrate accessibility as well as mobility on the substrate surface.

Adjusting Local Molecular Environment for Giant Ambient Thermal Contraction.

A low-energy triggered switch that can generate mechanoresponse has great technological potential. A submolecular moiety, S-dibenzocyclooctadiene (DBCOD) that is composed of a flexible eight-membered ring connecting to a phenyl ring at each end, undergoes a conformational change from twist-boat to chair under a low-energy stimulus such as near infrared irradiation, resulting in thermal contraction of DBCOD-based polymer. Experimental evidence corroborated by theoretical calculations indicates that introducing molecular asymmetry can reduce crystallinity significantly and consequently facilitate the kinetics of the conformational change. It has been demonstrated that the negative thermal expansion (NTE) coefficient of a DBCOD-based polymer system can be adjusted in a range from -1140 to -2350 ppm K-1 . -2350 ppm K-1 is ≈10 times better than the value reported by the second best NTE system.

An Elastic Monolithic Catalyst: A Microporous Metalloporphyrin-Containing Framework-Wrapped Melamine Foam for Process-Intensified Acyl Transfer.

The advent of conjugated microporous polymers (CMPs) has had significant impact in catalysis. However, the presence of only micropores in these polymers often imposes diffusion limitations, which has resulted in the low utilization of CMPs in catalytic reactions. Herein, the preparation of a foam-supporting CMP composite with interconnective micropores and macropores and elastic properties is reported. Metalloporphyrin-based CMP organogels are synthesized within the melamine foam by a room-temperature oxidative homocoupling reaction of terminal alkynes. Upon drying, the CMP-based xerogels tightly wrap the framework skeletons of the foam, while the foam cells are still open to allow for the preservation of elasticity and macroporosity. Such a hierarchical structure is efficient for acyl transfer, facilitates substrate diffusion within interpenetrative macropores and micropores, and could be used to intensify catalytic processes.