Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancerOA

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes(STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates(Ⅰand Ⅱ) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immuneactivating ST...     

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopesOA

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment.Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope opti...     

Late Ordovician Mass Extinction: Earth,fire and iceOA

The Late Ordovician Mass Extinction was the earliest of the ‘big’ five extinction events and the earliest to affect the trajectory of metazoan life. Two phases have been identified near the start of the Hirnantian period and in the middle. It was a massive taxonomic extinction, a weak phylogenetic extinction and a relatively benign ecological extinction. A rapid cooling, triggering a major ice age that reduced the temperature of surface waters, prompted a drop in sea level of some 100 m and intr...     

Cyclic-anion salt for high-voltage stable potassium-metal batteriesOA

Electrolyte anions are critical for achieving high-voltage stable potassium-metal batteries(PMBs).However,the common anions cannot simultaneously prevent the formation of ’dead K’ and the corrosion of Al current collector,resulting in poor cycling stability.Here,we demonstrate cyclic anion of hexafluoropropane-1,3-disulfonimide-based electrolytes that can mitigate the ’dead K’ and remarkably enhance the high-voltage stability of PMBs.Particularly,even using low salt concentration(0.8 M) and addi...     

Dual-ligand and hard-soft-acid-base strategies to optimize metal-organic framework nanocrystals for stable electrochemical cycling performanceOA

Most metal-organic frameworks(MOFs) hardly maintain their physical and chemical properties after exposure to acidic,neutral,or alkaline aqueous solutions,resulting in insufficient stability,therefore limiting their applications.Thus,the design and synthesis of stable size/morphology-controlled MOF nanocrystals is critical but challenging.In this study,dual-ligand and hard-soft-acid-base strategies were used to fabricate a variety of 3D pillared-layer [Ni(thiophene-2,5-dicarboxylate)(4,4’-bipyrid...     

Stability and dynamics of dendritic spines in macaque prefrontal cortexOA

Formation and elimination of synapses reflect structural plasticity of neuronal connectivity. Here we performed high-resolution two-photon imaging of dendritic spines in the prefrontal cortex of four macaque monkeys and found that spines were in general highly stable, with low percentages undergoing synaptic turnover. By observing the same spines at weekly intervals, we found that newly formed spines were more susceptible to elimination, with only 40% persisting over a period of months. Analyses...     

High-stability spherical lanthanide nanoclusters for magnetic resonance imagingOA

High-nuclear lanthanide clusters have shown great potential for the administration of high-dose mononuclear gadolinium chelates in magnetic resonance imaging(MRI). The development of high-nuclear lanthanide clusters with excellent solubility and high stability in water or solution has been challenging and is very important for expanding the performance of MRI. We used N-methylbenzimidazole-2-methanol(HL) and LnCl₃·6H₂O to synthesize two spherical lanthanide clusters, Ln     

Two-dimensional superconducting MoSi2N4(MoN)4n homologous compoundsOA

The number and stacking order of layers are two important degrees of freedom that can modulate the properties of 2D van der Waals(vdW) materials. However, the layers’ structures are essentially limited to the known layered 3D vdW materials. Recently, a new 2D vdW material, MoSi₂N₄, without known 3D counterparts, was synthesized by passivating the surface dangling bonds of non-layered 2D molybdenum nitride with elemental silicon, whose monolayer can be viewed as a monolayer ...     

A common variant in AAK1 reduces risk of noise-induced hearing lossOA

<正>Noise-induced hearing loss (NIHL) is one of the most common types of hearing loss and contributes to significant morbidity worldwide,as well as being the major cause of age-related hearing loss and tinnitus.The World Health Organization (WHO) estimates that 10%of the world’s population is exposed to sound levels that could potentially cause NIHL[1].It has been widely accepted that NIHL is a multifactorial genetic disorder with estimated heritability of 36%to 40%[2].Ideally,identificatio...     

Perspective on fluorescence cell imaging with ionophore-based ion-selective nano-optodes

Inorganic ions are ubiquitous in all kinds of cells with highly dynamic spatial and temporal distribution. Taking advantage of different types of fluorescent probes, fluorescence microscopic imaging and quantitative analysis of ion concentrations in cells have rapidly advanced. A family of fluorescent nanoprobes based on ionophores has emerged in recent years with the potential to establish a unique platform for the analysis of common biological ions including Na⁺, K⁺, Ca²⁺, Cl⁻, and so on. This article aims at providing a retrospect and outlook of ionophore-based ion-selective nanoprobes and the applications in cell imaging.     

Thermophysical properties of the regolith on the lunar far side revealed by the in situ temperature probing of the Chang’E-4 mission

Temperature probes onboard the Chang’E-4 (CE-4) spacecraft provide the first in situ regolith temperature measurements from the far side of the Moon. We present these temperature measurements with a customized thermal model and reveal the particle size of the lunar regolith at the CE-4 landing site to be ∼15 μm on average over depth, which indicates an immature regolith below the surface. In addition, the conductive component of thermal conductivity is measured as ∼1.53 × 10^–3 W m^–1 K^–1 on the surface and ∼8.48 × 10^–3 W m^–1 K^–1 at a depth of 1 m. The average bulk density is ∼471 kg m^–3 on the surface and ∼824 kg m^–3 in the upper 30 cm of the lunar regolith. These thermophysical properties provide important additional ‘ground truth’ at the lunar far side, which is critical for the future analysis and interpretation of global temperature observations.     

Serrated lithium fluoride nanofibers-woven interlayer enables uniform lithium deposition for lithium-metal batteries

The uncontrollable formation of Li dendrites has become the biggest obstacle to the practical application of Li-metal anodes in high-energy rechargeable Li batteries. Herein, a unique LiF interlayer woven by millimeter-level, single-crystal and serrated LiF nanofibers (NFs) was designed to enable dendrite-free and highly efficient Li-metal deposition. This high-conductivity LiF interlayer can increase the Li⁺ transference number and induce the formation of ‘LiF–NFs-rich’ solid–electrolyte interface (SEI). In the ‘LiF–NFs-rich’ SEI, the ultra-long LiF nanofibers provide a continuously interfacial Li⁺ transport path. Moreover, the formed Li–LiF interface between Li-metal and SEI film renders low Li nucleation and high Li⁺ migration energy barriers, leading to uniform Li plating and stripping processes. As a result, steady charge–discharge in a Li//Li symmetrical cell for 1600 h under 4 mAh cm⁻² and 400 stable cycles under a high area capacity of 5.65 mAh cm⁻² in a high-loading Li//rGO–S cell at 17.9 mA cm⁻² could be achieved. The free-standing LiF–NFs interlayer exhibits superior advantages for commercial Li batteries and displays significant potential for expanding the applications in solid Li batteries.     

ZnO-based micromotors fueled by CO2: the first example of self-reorientation-induced biomimetic chemotaxis

Synthetic chemotactic micro/nanomotors are envisioned to actively ‘seek out’ targets by following specific chemicals, but they are mainly powered by bioincompatible fuels and only show pseudochemotaxis (or advanced chemokinesis) due to their weak self-reorientation capabilities. Here we demonstrate that synthetic ZnO-based Janus micromotors can be powered by the alternative biocompatible fuel of CO₂, and further provide the first example of self-reorientation-induced biomimetic chemotaxis using them. The ZnO-based micromotors are highly sensitive to dissolved CO₂ in water, which enables the corrosion of ZnO to continuously occur by providing H⁺ through hydration. Thus, they can autonomously move even in water exposed to air based on self-diffusiophoresis. Furthermore, they can sense the local CO₂ gradient and perform positive chemotaxis by self-reorientations under the phoretic torque. Our discovery opens a gate to developing intelligent micro/nanomotors powered by, and sensitive to, biocompatible atmospheric or endogenous gaseous chemicals for biomedical and environmental applications.     

Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium (KATP)

The current aggregation-induced emission luminogens (AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in the hydrophilic biosystem with ‘always-on’ fluorescence or unspecific aggregation in the lipophilic organelle with prematurely activated fluorescence. Herein, we report an unprecedented ‘amphiphilic AIEgen’ sensor QM-SO₃-ER based on the AIE building block of quinoline-malononitrile (QM). The introduced hydrophilic sulfonate group can well control the specific solubility in a hydrophilic system with desirable initial ‘fluorescence-off’ state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the adenosine triphosphate (ATP)-sensitive potassium (K_ATP) on the endoplasmic reticulum (ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time settled down the predicament of unexpected ‘always-on’ fluorescence in the aqueous system and the untargetable aggregation signal in the lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgens'' targetability.     

Concentration and content

One of the more frequent activities in health sciences is the measurement of biological quantities. Frequently, when reading biomedical books and journals some confusion on the metrological meaning of biological quantities related to the concepts ‘concentration’ and ‘content’ may be observed. Classically, a concentration is an amount of any type per volume of liquid or gas system, whereas content is an amount of any type per mass of liquid or gas or solid system. However the concepts ‘concentration’ and ‘content’ alone are still ambiguous because, depending on the type of amount of the component (analyte) per volume or mass of a system, there are different types of concentrations and contents. This article attempts to give a clarification of these concepts, mainly based on international recommendations about nomenclature and terminology of metrology, chemistry and clinical laboratory sciences.     

Post-ingestion conversion of dietary indoles into anticancer agents

There are health benefits from consuming cruciferous vegetables that release indole-3-carbinol (I3C), but the in vivo transformation of I3C-related indoles remains underinvestigated. Here we detail the post-ingestion conversion of I3C into antitumor agents, 2-(indol-3-ylmethyl)-3,3^′-diindolylmethane (LTr1) and 3,3^′-diindolylmethane (DIM), by conceptualizing and materializing the reaction flux derailing (RFD) approach as a means of unraveling these stepwise transformations to be non-enzymatic but pH-dependent and gut microbe-sensitive. In the upper (or acidic) gastrointestinal tract, LTr1 is generated through Michael addition of 3-methyleneindolium (3MI, derived in situ from I3C) to DIM produced from I3C via the formaldehyde-releasing (major) and CO₂-liberating (minor) pathways. In the large intestine, ‘endogenous’ I3C and DIM can form, respectively, from couplings of formaldehyde with one and two molecules of indole (a tryptophan catabolite). Acid-producing gut bacteria such as Lactobacillus acidophilus facilitate the H⁺-promotable steps. This work updates our understanding of the merits of I3C consumption and identifies LTr1 as a drug candidate.     

Li-ion battery material under high pressure: amorphization and enhanced conductivity of Li4Ti5O12

Lithium titanium oxide (Li₄Ti₅O₁₂, LTO), a ‘zero-strain’ anode material for lithium-ion batteries, exhibits excellent cycling performance. However, its poor conductivity highly limits its applications. Here, the structural stability and conductivity of LTO were studied using in situ high-pressure measurements and first-principles calculations. LTO underwent a pressure-induced amorphization (PIA) at 26.9 GPa. The impedance spectroscopy revealed that the conductivity of LTO improved significantly after amorphization and that the conductivity of decompressed amorphous LTO increased by an order of magnitude compared with its starting phase. Furthermore, our calculations demonstrated that the different compressibility of the LiO₆ and TiO₆ octahedra in the structure was crucial for the PIA. The amorphous phase promotes Li⁺ diffusion and enhances its ionic conductivity by providing defects for ion migration. Our results not only provide an insight into the pressure depended structural properties of a spinel-like material, but also facilitate exploration of the interplay between PIA and conductivity.     

Cascade-responsive nanobomb with domino effect for anti-tumor synergistic therapies

The development of reactive oxygen species (ROS) generation agents that can selectively produce sufficient ROS at the tumor site without external energy stimulation is of great significance for the further clinical application of ROS-based therapies. Herein, we designed a cascade-responsive ROS nanobomb (ZnO₂@Ce6/CaP@CPPO/BSA, designated as Z@Ce6/CaP@CB) with domino effect and without external stimulation for the specific generation of multiple powerful ROS storms at the tumor site. The calcium phosphate shell and ZnO₂ core gradually degrade and release Ca²⁺, Zn²⁺ and hydrogen peroxide (H₂O₂) under acid stimulation. On the one hand, Zn²⁺ can enhance the generation of endogenous superoxide anions (·O₂^–) and H₂O₂ through the inhibition of the mitochondrial electron transport chain. On the other hand, the generation of large amounts of exogenous H₂O₂ can cause oxidative damage to tumor cells and further activate bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO)-mediated chemiexcited photodynamic therapy. In addition, the oxidative stress caused by the generated ROS can lead to the uncontrolled accumulation of Ca²⁺ in cells and further result in Ca²⁺ overload-induced cell death. Therefore, the introduction of Z@Ce6/CaP@CB nanobombs triggered the ‘domino effect’ that caused multiple heavy ROS storms and Ca²⁺ overload in tumors and effectively activated anti-tumor immune response.     

Increasing Glucose Concentrations Interfere with Estimation of Electrolytes by Indirect Ion Selective Electrode Method

The estimation of electrolytes like sodium (Na⁺), potassium (K⁺) and chloride (Cl⁻) using direct and indirect ion-selective electrodes (ISE) is a routine laboratory practice. Interferents like proteins, triglycerides, drugs etc. are known to affect the results. The present study was designed to look into the effect of increasing glucose concentrations on estimation of Na⁺, K⁺ and Cl⁻ by direct and indirect ISE. Pooled sera was mixed with glucose stock solution (20 g/dL) prepared in normal saline to obtain glucose concentrations ranging from ~100 to ~5000 mg/dL. Na⁺, K⁺ and Cl⁻ levels were estimated by direct and indirect ISE analyzers and results were statistically analysed using ANOVA and Pearson’s correlation. Similar experiment was also performed in 24 h urine sample from healthy subjects. Significant difference was observed between Na⁺ and Cl⁻ measurements by direct and indirect ISE, with indirect ISE values being consistently higher than direct ISE. Besides this, significant difference was observed amongst Na⁺ and Cl⁻ values from baseline values obtained by indirect ISE at glucose concentrations ≥2486 mg/dL. However, no such difference was observed with direct ISE. Na⁺ and Cl⁻ estimation by indirect ISE showed significant negative correlation with glucose concentration, more so, above ~2000 mg/dL. K⁺, however, showed no significant difference with varying glucose. Similar results were observed in 24 h urine samples with a significant difference observed amongst Na⁺ and Cl⁻ values at ≥2104 mg/dL glucose. Thus we conclude that high glucose concentrations interfere significantly in estimation of Na⁺ and Cl⁻ by indirect ISE in serum as well as urine.

Electronic supplementary material

The online version of this article (doi:10.1007/s12291-015-0522-0) contains supplementary material, which is available to authorized users.