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LL-37, the only human host cathelicidin peptide, is proposed to be able to induce host cell apoptosis through mitochondrial membrane permeabilization (MMP). Detailed pathways of the LL-37-triggered MMP are however still disputed. It is generally believed that cationic peptides permeate a membrane mostly in conditions of micromolar peptide concentrations and negatively charged membranes, which are not usually satisfied in the mitochondrial circumstance. Herein, using a variety of single-molecule techniques, we show that nanomolar LL-37 specifically induces permeability of a phosphoethanolamine (PE)-rich biomimetic mitochondrial membrane in a protein-independent manner. The insertion dynamics of single LL-37 molecules exhibit different metastable states in bilayers composed of different lipids. Moreover, the PE lipids significantly facilitate adsorption and accumulation of LL-37 on the PE-rich bilayer, and produce deeper insertion of peptide oligomers, especially tetramers, into the bilayer. This work offers an alternative pathway of the LL-37-triggered MMP and apoptosis.

Characterization of biomolecular dynamics at cellular membranes lags far behind that in solutions because of challenges to measure transmembrane trafficking with subnanometer precision. Herein, by introducing nonfluorescent quenchers into extracellular environment of live cells, we adopted Förster resonance energy transfer from one donor to multiple quenchers to measure positional changes of biomolecules in plasma membranes. We demonstrated the method by monitoring flip-flops of individual lipids and by capturing transient states of the host defense peptide LL-37 in plasma membranes. The method was also applied to investigate the interaction of the necroptosis-associated protein MLKL with plasma membranes, showing a few distinct depths of MLKL insertion. Our method is especially powerful to quantitate the dynamics of proteins at the cytosolic leaflets of plasma membranes which are usually not accessible by conventional techniques. The method will find wide applications in the systematic analysis of fundamental cellular processes at plasma membranes.

Beijing-Tianjin-Hebei region is a capital economic circle for the future. Promoting the coordinated development of its population, economy, resources and environment is a major national strategy. And as towns and cities continue to expand, the volume of construction waste is gradually expanding, posing a major challenge to the sustainable development of the construction industry. In order to solve this problem, this paper used portable XRF to realize the on-site rapid monitoring of heavy metals in construction waste, and the correlation analysis result was R2 = 0.9622. The visualization of enrichment factor evaluation results was realized through ArcGIS. Beijing-Tianjin-Hebei region is mainly polluted by heavy metal elements Cr, Zn, Pb and Hg, showing regional pollution characteristics. The reason can be traced to the heavy industrial production in Tangshan, which is in line with the principle of industrial ecology. The results of leaching toxicity and cation anion analysis showed that the construction waste in Beijing-Tianjin-Hebei region had environmental risks to the surrounding surface water and groundwater. The resource treatment and disposal path were determined by means of XRD, ternary phase diagram and oxide composition analysis to avoid secondary pollution. This study explores the environmental properties and resource utilization pathways of construction waste in the Beijing-Tianjin-Hebei region, laying the foundation for research work on construction waste in the development of national urban agglomerations, effectively solving regional environmental pollution problems, and promoting the sustainable development of the construction industry.

Thermodynamics and structural transitions on protein surfaces remain relatively understudied and poorly understood. Wrapping of DNA on proteins provides a paradigm for studying protein surfaces. We used magnetic tweezers to investigate a prototypical DNA-interacting protein, i.e., the single-stranded DNA binding protein (SSB). SSB binds DNA with distinct binding modes the mechanism of which is still elusive. The measured thermodynamic parameters relevant to the SSB-DNA complex are salt-dependent and discontinuous at the bind-mode transitions. Our data indicate that free SSB undergoes salt-induced first-order structural transitions. The conclusion was supported by the infrared spectroscopy of SSB in salt solutions. Ultrafast infrared spectroscopy further suggests that the transitions are correlated with surface salt bridges. Our work not only unravels a long-standing mystery of the different binding site sizes of SSB, but also would inspire interests in thermodynamics of protein surfaces.

It is a big challenge to measure position changes of biomolecules in the direction normal to the plasma membranes of living cells. We developed a one donor-multiple quenchers Fӧrster resonance energy transfer method by using non-fluorescent quenchers in the extracellular environment. It senses subnanometer position changes of a fluorophore-labeled biomolecule in the plasma membrane. The method was validated by monitoring flip-flops of individual lipid molecules incorporated in plasma membranes. We studies membrane perforation by a host defense peptide from the extracellular side and found that the pore-forming peptide is dynamic, switching among different insertion depths. The method is especially useful in studying interactions of membrane proteins with the inner surfaces of plasma membranes. Our method will find wide applications in systematic analysis of fundamental cellular processes at plasma membranes.

Correction for ‘Nanomolar LL-37 induces permeability of a biomimetic mitochondrial membrane’ by Xin Jiang et al., Nanoscale, 2022, https://doi.org/10.1039/d2nr05409d.

It is challenging to assess protein-membrane interactions because of the lack of appropriate tools to detect position changes of single proteins in the ∼4 nm range of biological membranes. We developed an assay recently, termed surface-induced fluorescence attenuation (SIFA). It is able to track both vertical and lateral dynamic motion of singly labeled membrane proteins in supported lipid bilayers. Similar to the FRET (fluorescence resonance energy transfer) principle, SIFA takes advantage of the energy transfer from a fluorophore to a light-absorbing surface to determine the distance at 2-8 nm away from the surface. By labeling a protein with a proper fluorophore and using graphene oxide as a two-dimensional quencher, we showed that SIFA is capable of monitoring three-dimensional movements of the fluorophore-labeled protein not only inside but also above the lipid bilayer atop the graphene oxide. Our data show that SIFA is a well-suited method to study the interplay between proteins and membranes.

Visualizing and tracking mitochondrial changes is the key to understand the processes of diseases related to mitochondria, which is meaningful to physiology, pathology, and pharmacology. So, a great deal of mitochondrial probes was designed and synthesized according to the principle that probes with a positive charge can target mitochondria through mitochondrial membrane potential (MMP). However, these traditional mitochondrial probes are not able to visualize and track mitochondrial changes, because their targeting abilities depend on high MMP. Once MMP decreases, they will leak from mitochondria. Herein, we designed and synthesized a red-emitting molecule rotor (SQ, sensitive to viscosity) that could visualize mitochondria with high-fidelity. The rotor was able to firmly immobilize in mitochondrial inner membrane through the cooperation of MMP and the high viscosity property of mitochondrial membrane, and it could still stain mitochondria with long-term regardless of MMP changes. Hence, the probe is able to real-time image and distinguish four kinds of mitochondria with high-fidelity in muscle tissues. In addition, SQ can monitor mitochondrial autophagy in real time. These results demonstrate that SQ is a powerful tool for high-fidelity visualizing and long-term tracking mitochondria in vitro and in vivo.

Hexavalent chromium (Cr(VI)) pollution is related to human health, and the detection of its concentration has a decisive effect on pollution treatment. In this work, we designed a Cr2O72− sensor P(Fmoc-Osu) and applied it in farmland. In the boron trifluoride diethyl etherate solution, the monomer Fmoc-Osu was electropolymerized and obtained its conjugated polymer P(Fmoc-Osu). The introduction of succinimide and carbonic ester group in side chain enabled it to show high selectivity to Cr2O72− in comparison to anions and twenty amino acids. Furthermore, by taking advantage of the signal amplification effect of a conjugated polymer, P(Fmoc-Osu) could analyze Cr2O72− in trace amounts and the limit of detection was 8.3 fM. For agricultural application, we employed it in farmland water, soil, Chinese cabbage, carrot and the results showed a satisfactory result. All these results showed that P(Fmoc-Osu) is an efficient tool to detect Cr2O72− in practical application.

The permeabilization of organelle membranes by BCL-2 family proteins is a pivotal step during the regulation of apoptosis; the underlying mechanisms remain unclear. Based on the fluorescence attenuation by graphene oxide, we developed a single-molecule imaging method termed surface-induced fluorescence attenuation (smSIFA), which enabled us to track both vertical and lateral kinetics of singly labeled BCL-2 family protein tBid during membrane permeabilization. We found that tBid monomers lie shallowly on the lipid bilayer, where they self-assemble to form oligomers. During the initiation phase of self-assembly, the two central hydrophobic helices (α6 and α7) of tBid insert halfway into the phospholipid core, while the other helices remain on the surface. In oligomerized tBid clusters, α6 and α7 prefer to float up, and the other helices may sink to the bottom of the membrane and cause the formation of transient two-dimensional, micelle-like pore structures, which are responsible for the permeabilization of membranes and the induction of apoptosis. Our results shed light on the understanding of tBid-induced apoptosis, and this nanotechnology-based smSIFA approach could be used to dissect the kinetic interaction between membrane protein and lipid bilayer at the single-molecule level with subnanometer precision.

On May 31, 2017, the 25th Meeting of the European Society of Thoracic Surgeons (ESTS) successfully ended, after a dense 4-day agenda blending a superb scientific and educational program.

Curcumin, a polyphenolic antioxidant derived from the turmeric root has undergone extensive preclinical development, showing remarkable efficacy in wound repair, cancer and inflammatory disorders. This review addresses the rationale for its use in neurodegenerative disease, particularly Alzheimer’s disease (AD). Curcumin is a pleiotropic molecule, which not only directly binds to and limits aggregation of the β-sheet conformations of amyloid characteristic of many neurodegenerative diseases but also restores homeostasis of the inflammatory system, boosts the heat shock system to enhance clearance of toxic aggregates, scavenges free radicals, chelates iron and induces anti-oxidant response elements. Although curcumin corrects dysregulation of multiple pathways, it may exert many effects via a few molecular targets. Pharmaceutical development of natural compounds like curcumin and synthetic derivatives have strong scientific rationale, but will require overcoming various hurdles including; high cost of trials, concern about profitability and misconceptions about drug specificity, stability and bioavailability.

Low-voltage, low-cost, high-performance monolayer field-effect transistors are demonstrated, which comprise a densely packed, long-range ordered monolayer spin-coated from core-cladding liquid-crystalline pentathiophenes and a solution-processed high-k HfO2-based nanoscale gate dielectric. These monolayer field-effect transistors are light-sensitive and are able to function as reporters to convert analyte binding events into electrical signals with ultrahigh sensitivity (approximate to 10 ppb).

Organic two-dimensional (2D) crystals are fundamentally important for development of future devices. Despite that more than a half of man-made products contain polymers, 2D crystals consisting of long linear chains have yet to be explored. Here we report on the fabrication of 2D polyaniline (PANI) crystals via rational electrochemical polymerization followed by liquid-phase exfoliation. The 2D PANI is molecularly thin (∼0.8 nm) and composed of PANI chains with a number-average molecular weight of ∼31 000. The chains are parallel to each other with the benzene rings standing almost vertically to the surface, implying a face-to-face arrangement of the neighboring chains held together by abundant π–π interactions augmented with hydrogen bonds. The 2D PANI can be readily transferred to various solid surfaces and exhibit interesting electrical and optical properties, suggesting that they would be potentially useful in photoelectronic devices and other applications.

Research on the dynamics of single-membrane proteins remains underdeveloped due to the lack of proper approaches that can probe in real time the protein's insertion depth in lipid bilayers. Here we report a single-molecule visualization method to track both vertical insertion and lateral diffusion of membrane proteins in supported lipid bilayers by exploiting the surface-induced fluorescence attenuation (SIFA) of fluorophores. The attenuation follows a d−4 dependency, where d is the fluorophore-to-surface distance. The method is validated by observing the antimicrobial peptide LL-37 to transfer among five transmembrane positions: the surface, the upper leaflet, the centre, the lower leaflet and the bottom of the lipid bilayer. These results demonstrate the power of SIFA to study protein-membrane interactions and provide unprecedented in-depth understanding of molecular mechanisms of the insertion and translocation of membrane proteins., Assessing protein localization within lipid membranes is problematic. Here, the authors describe a single molecule visualization method based on surface-induced fluorescence attenuation (SIFA) to determine the insertion depth and lateral diffusion of a peptide in a lipid bilayer.

Organic field-effect transistors (OFETs) featuring a photoactive hybrid bilayer dielectric (PHBD) that comprises a self-assembled monolayer (SAM) of photochromic diarylethenes (DAEs) and an ultrathin solution-processed hafnium oxide layer are described here. We photoengineer the energy levels of DAE SAMs to facilitate the charging and discharging of the interface of the two dielectrics, thus yielding an OFET that functions as a nonvolatile memory device. The transistors use light signals for programming and electrical signals for erasing (≤3 V) to produce a large, reversible threshold-voltage shift with long retention times and good nondestructive signal processing ability. The memory effect can be exercised by more than 10(4) memory cycles. Furthermore, these memory cells have demonstrated the capacity to be arrayed into a photosensor matrix on flexible plastic substrates to detect the spatial distribution of a confined light and then store the analog sensor input as a two-dimensional image with high precision over a long period of time.

Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral and cellular changes. We previously reported that long term (5–11 days) TSD in the rat, by the disk-over-water method, decreases the activity of the antioxidant enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain insight into the mechanisms causing cognitive impairment, here we explore the early associations between metabolic activity, antioxidant responses and working memory (one form of cognitive impairment). Specifically we investigated the impact of short term (6 h) TSD, by gentle handling, on the levels of the endogenous antioxidant, total glutathione (GSHt), and the activities of the antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short term TSD had no significant impact on SOD activity, but increased GSHt levels in the rat cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus and cerebellum. We also observed increased activity of hexokinase, (HK), the rate limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We further showed that 6h of TSD leads to increased exploratory behavior to a new environment, without impairing spontaneous alternation behavior (SAB) in the Y maze. We conclude that acute (6h) sleep loss may trigger compensatory mechanisms (like increased antioxidant responses) that prevent initial deterioration in working memory.

The dysregulation of glycogen synthase kinase-3 (GSK3) has been implicated in Alzheimer disease (AD) pathogenesis and in Abeta-induced neurotoxicity, leading us to investigate it as a therapeutic target in an intracerebroventricular Abeta infusion model. Infusion of a specific GSK3 inhibitor SB216763 (SB) reduced a downstream target, phospho-glycogen synthase 39%, and increased glycogen levels 44%, suggesting effective inhibition of enzyme activity. Compared to vehicle, Abeta increased GSK3 activity, and was associated with elevations in levels of ptau, caspase-3, the tau kinase phospho-c-jun N-terminal kinase (pJNK), neuronal DNA fragmentation, and gliosis. Co-infusion of SB corrected all responses to Abeta infusion except the induction of gliosis and behavioral deficits in the Morris water maze. Nevertheless, SB alone was associated with induction of neurodegenerative markers and behavioral deficits. These data support a role for GSK3 hyperactivation in AD pathogenesis, but emphasize the importance of developing inhibitors that do not suppress constitutive activity.

Highly oriented crystalline Zn(OH)2/p-aminobenzoic acid nanolaminates are fabricated on solid supports by cathodic electrodeposition. The growth condition is very mild, involving no organic solvent. The nanolaminates have superhydrophobic surface and are transparent in the range of the visible light. The nanolaminates electrodeposited on silicon substrates behave like multiquantum well structures, exhibiting unique optical properties which are not seen in either zinc hydroxide or p-aminobenzoic acid crystals.

Controllable depositing of relatively thick inorganic sublayers into organic templates to fabricate organic-inorganic superlattices is of great importance. We report a novel approach to fabricating phospholipid/Ni(OH)(2) superlattices by electrochemical deposition of the inorganic component into solid-supported multilamellar templates. The well-ordered and highly oriented multilamellar templates are produced by spreading small drops of lipid solution on silicon surfaces and letting the solvent evaporate slowly. The templates which are used as working electrodes preserve the lamellar structure in the electrolyte solution. The resulting superlattices are highly oriented. The thickness of the nickel hydroxide is controlled by the concentration of nickel ions in the electrolyte bath. The electron density profiles derived from the X-ray diffraction data reveal that the thickness of the nickel hydroxide sublayers increases from 15 to 27 A as the concentration of nickel nitrate increases from 0.005 mol/L to 0.08 mol/L. We expect that the new method can be extended to depositing a variety of inorganic components including metals, oxides, and semiconductors.

On July 14, 2017, the Guangzhou Blood Safety Conference successfully ended, after a 2-day scientific and compact agenda. The event took place in Guangzhou, a beautiful city located in South China. With the presence of prestigious local and foreign experts from fields of blood safety, epidemiology, etc., the meeting was dedicated to providing comprehensive-in-depth, detailed overview of new, controversial, challenging themes, advances, and inspirations in blood safety.

The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected. Background: Various types of Tau aggregates in AD brains may differentially impact neurodegeneration. Results: Curcumin selectively suppresses soluble Tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits. Conclusion: A drug increasing HSPs involved in Tau clearance reduced Tau dimers and improved cognition. Significance: Curcumin that reduced Tau dimers and increased molecular chaperones was efficacious without altering insoluble Tau.

Interface modification is an effective and promising route for developing functional organic field-effect transistors (OFETs). In this context, however, researchers have not created a reliable method of functionalizing the interfaces existing in OFETs, although this has been crucial for the technological development of high-performance CMOS circuits. Here, we demonstrate a novel approach that enables us to reversibly photocontrol the carrier density at the interface by using photochromic spiropyran (SP) self-assembled monolayers (SAMs) sandwiched between active semiconductors and gate insulators. Reversible changes in dipole moment of SPs in SAMs triggered by lights with different wavelengths produce two distinct built-in electric fields on the OFET that can modulate the channel conductance and consequently threshold voltage values, thus leading to a low-cost noninvasive memory device. This concept of interface functionalization offers attractive new prospects for the development of organic electronic devices with tailored electronic and other properties.

We use the X-ray diffraction method to examine the thermotropic phase behavior of multilamellar membranes of dioleoylphosphatidylcholine. We find that when the temperature is reduced from room temperature to below 0 degrees C, both the lipid bilayers and the amount of water in the bilayers increase. But the interbilayer distance descends abruptly at a certain temperature between -6 and -15 degrees C, the actual value depending on the relative humidity of the atmosphere, solely due to the thinning of the water layer, d(w). There are several L(alpha) and L(c) phase coexistence states both in the cooling process and in the heating process. In the cooling process, only a part of the lipid molecules accomplish the L(alpha)-to-L(c) main phase transition at -16 degrees C, with the rest of the lipids being frozen down to a very low temperature. In the heating process, however, these frozen lipid molecules are able to move to complete the L(alpha)-to-L(c) main phase transition at -12 degrees C. The reverse of the main phase transition begins at -9 degrees C and is completed at -5 degrees C, after which the water is absorbed into the lipid bilayer to increase the thickness of the water layer, while the thickness of the lipid membranes remain unchanged. This process continues until all the ice on top of the samples melts.

Lipoplexes are composed of lipids and nucleic acids and have an ordered multilamellar structure with a periodic 1D array of parallel nucleic acid strands in the lipid bilayers. We report a low-angle X-ray diffraction study on solid-supported lipoplex films composed of synthertic single-stranded oligodeoxynucleotides (ssODN) and lipids, The ssODN molecules distribute sparsely in the headgroup regions when the weight concentration of the ssODN in the lipoplex is low. The lipoplex separates into two phases, an ODN-poor phase and an ODN-rich phase, when the weight concentration of the ssODN is increased beyond a level at which the ssODN molecules contact each other so that sonic regions of the lipid bilayers must accommodate two layers of the ssODN. The phase separation is a results of the fusion of such regions to minimize the total interfacial energy of the system. The ssODN molecules distort the lipid bilayers in the ODN-poor phase. The local area per lipid molecule is increased by the distortions so that the interbilayer distance of the lipoplex film is smaller than that of the lipid film without the ssODN. The ODN-rich phase has a much larger interbilayer distance because two layers of ssODN are intercalated into each lipid bilayer. The ssODN molecules are tightly compacted, and the lipid bilayers are not distorted in the ODN-rich phase.

We report on the fabrication of a subnanometer-thick epitaxial PbS film on polydiacetylene (PDA) substrate. The film is formed by cation-absorption in PbCl2 solution followed by sulfidation in mixed H2S/N2 gas, exhibiting a flat and smooth surface morphology. The strong adsorbate-surface interaction between the lead hydrolysis complexes and the carboxyl headgroups on the surface of PDA accounts for such a growth mode. We further demonstrate that such an ultrathin film can be used as a buffer layer for both homo- and heteroepitaxial growth of sulfide films. The X-ray and electron diffraction results reveal that the (001) planes of PbS are parallel to the surface of PDA and the (110) planes of PbS are parallel to the (110) planes of PDA.