Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma.

Although the spatial characteristics within the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) have been identified, the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear. Using spatial transcriptomics (ST) and single-cell RNA-sequencing (scRNA-seq) data from multi-regional LUAD biopsies, consisting of tumor core, tumor edge and normal area, we sought to delineate the spatial heterogeneity and driving factors of cell co-localization. Two cancer cell sub-clusters (Cancer_c1 and Cancer_c2), associated with LUAD initiation and metastasis respectively, exhibit distinct spatial distributions and immune cell colocalizations.

Vertical growth of rhenium disulfide on rGO empowers multi-signal amplification for ultrasensitive MiRNA-21 detection.

Unique rhenium disulfide/reduced graphene oxide (ReS/rGO) nanoframeworks were synthesized with a hierarchical layered and porous structure for the ultrasensitive electrochemical detection of microRNA-21 (miRNA-21) by empowering multi-signal amplification strategy of catalytic hairpin self-assembly-hybridization chain reaction (CHA-HCR). The layered and porous nanostructures endowed ReS/rGO with a larger specific surface area and more active sites through connecting vertical ReS with rGO which was preferable for promoting the electron transfer over electrode surface because of a conductive network. This nanoframework facilitated the loading of adequate gold nanoparticles to fix the capture probe via Au-S bond.

Cocatalysis of catalytic hairpin assembly and ternary heterojunction BiS@MoS@BiMoO promotes ultra-sensitive electrochemical of detection MiRNA-21.

Ternary heterojunction BiS/MoS/BiMoO was designed as a signal probe to develop a dual signal amplification strategy empowered electrochemical biosensor for sensitive miRNA-21 detection by combining with catalytic hairpin assembly (CHA). The combination of the BiS/MoS/BiMoO heterojunction as a tracer indication probe and the CHA amplification strategy not only took fully use of the highly dense nanowire interwoven structure and superior active region of the probe, but also endowed the ability to improve the molecular hybridization efficiency by collision, which significantly avoided the cumbersome chain design and greatly simplified the step-by-step construction of the electrode surface. Hairpin H1 was first added dropwise to the gold nanoparticle-decorated electrode surface, and then opened by the introduced miRNA-21 to initiate the specific hybridization.

Electronic Structure Modification of MnO Nanosheet Arrays with Enhanced Water Oxidation Activity and Stability by Nitrogen Plasma.

The strategic design of catalysts for the oxygen evolution reaction (OER) is crucial in tackling the substantial energy demands associated with hydrogen production in electrolytic water splitting. Despite extensive research on birnessite (δ-MnO) manganese oxides to enhance catalytic activity by modulating Mn species, the ongoing challenge is to simultaneously stabilize Mn while improving overall activity. Herein, oxygen (O) vacancies and nitrogen (N) doping have been simultaneously introduced into the MnO through a simple nitrogen plasma approach, resulting in efficient OER performance.

Cubic NaBiTiO nanoperovskite significantly expands the application of sensitive immunosensor for the detection of carcinoembryonic antigen.

Nanosized sodium bismuth perovskite titanate (NBT) was synthesized and first used as the electrochemical immune sensing platform for the sensitive detection of carcinoembryonic antigen (CEA). Gold nanoparticles (Au NPs) grew on the surface of NBT through forming Au-N bond to obtain Au@NBT, and a label-free electrochemical immunosensor was proposed using Au@NBT as an immunosensing recognizer towards CEA. The well-ordered crystal structure of NBT was not changed at all after the modification of Au NPs outside, but significantly improved the conductivity, catalytic activity, and biocompatibility of the Au@NBT-modified electrode.

Nanomaterials promote the fast development of electrochemical MiRNA biosensors.

Cancer has become the leading cause of death worldwide. In recent years, molecular diagnosis has demonstrated great potential in the prediction and diagnosis of cancer. MicroRNAs (miRNAs) are short oligonucleotides that regulate gene expression and cell function and are considered ideal biomarkers for cancer detection, diagnosis, and patient prognosis.

Activity-Induced Cortical Glutamatergic Neuron Nascent Proteins.

Neuronal activity initiates signaling cascades that culminate in diverse outcomes including structural and functional neuronal plasticity, and metabolic changes. While studies have revealed activity-dependent neuronal cell type-specific transcriptional changes, unbiased quantitative analysis of cell-specific activity-induced dynamics in newly synthesized proteins (NSPs) synthesis has been complicated by cellular heterogeneity and a relatively low abundance of NSPs within the proteome in the brain. Here we combined targeted expression of mutant MetRS (methionine tRNA synthetase) in genetically defined cortical glutamatergic neurons with tight temporal control of treatment with the noncanonical amino acid, azidonorleucine, to biotinylate NSPs within a short period after pharmacologically induced seizure in male and female mice.

Quantitative BONCAT Allows Identification of Newly Synthesized Proteins after Optic Nerve Injury.

Retinal ganglion cells (RGCs) die after optic nerve trauma or in degenerative disease. However, acute changes in protein expression that may regulate RGC response to injury are not fully understood, and detailed methods to quantify new protein synthesis have not been tested. Here, we develop and apply a new quantitative measure of newly synthesized proteins to examine changes occurring in the retina after optic nerve injury.

Quantitative transportomics identifies Kif5a as a major regulator of neurodegeneration.

Many neurons in the adult central nervous system, including retinal ganglion cells (RGCs), degenerate and die after injury. Early axon protein and organelle trafficking failure is a key component in many neurodegenerative disorders yet changes to axoplasmic transport in disease models have not been quantified. We analyzed early changes in the protein 'transportome' from RGC somas to their axons after optic nerve injury and identified transport failure of an anterograde motor protein Kif5a early in RGC degeneration.

Proteomic screen reveals diverse protein transport between connected neurons in the visual system.

Intercellular transfer of toxic proteins between neurons is thought to contribute to neurodegenerative disease, but whether direct interneuronal protein transfer occurs in the healthy brain is not clear. To assess the prevalence and identity of transferred proteins and the cellular specificity of transfer, we biotinylated retinal ganglion cell proteins in vivo and examined biotinylated proteins transported through the rodent visual circuit using microscopy, biochemistry, and mass spectrometry. Electron microscopy demonstrated preferential transfer of biotinylated proteins from retinogeniculate inputs to excitatory lateral geniculate nucleus (LGN) neurons compared with GABAergic neurons.

Multi-biomarker is an early-stage predictor for progression of Coronavirus disease 2019 (COVID-19) infection.

Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease.

Temporal Quantitative Profiling of Newly Synthesized Proteins during Aβ Accumulation.

Accumulation of aggregated amyloid beta (Aβ) in the brain is believed to impair multiple cellular pathways and play a central role in Alzheimer's disease pathology. However, how this process is regulated remains unclear. In theory, measuring protein synthesis is the most direct way to evaluate a cell's response to stimuli, but to date, there have been few reliable methods to do this.

Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.

Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors. Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined. Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.

Containing misinformation spreading in temporal social networks.

Many researchers from a variety of fields, including computer science, network science, and mathematics, have focused on how to contain the outbreaks of Internet misinformation that threaten social systems and undermine societal health. Most research on this topic treats the connections among individuals as static, but these connections change in time, and thus social networks are also temporal networks. Currently, there is no theoretical approach to the problem of containing misinformation outbreaks in temporal networks.

The Retinal Ganglion Cell Transportome Identifies Proteins Transported to Axons and Presynaptic Compartments in the Visual System In Vivo.

The brain processes information and generates cognitive and motor outputs through functions of spatially organized proteins in different types of neurons. More complete knowledge of proteins and their distributions within neuronal compartments in intact circuits would help in the understanding of brain function. We used unbiased in vivo protein labeling with intravitreal NHS-biotin for discovery and analysis of endogenous axonally transported proteins in the visual system using tandem mass spectrometric proteomics, biochemistry, and both light and electron microscopy.

Quantitative analysis of newly synthesized proteins.

Measuring proteome response to perturbations is critical for understanding the underlying mechanisms involved. Traditional quantitative proteomic methods are limited by the large numbers of proteins in the proteome and the mass spectrometer's dynamic range. A previous method uses the biorthogonal reagent azidohomoalanine (AHA), a methionine analog, for labeling, enrichment and detection of newly synthesized proteins (NSPs).

Quantitative temporal analysis of protein dynamics in cardiac remodeling.

Cardiac remodeling (CR) is a complex dynamic process common to many heart diseases. CR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of CR, but greater insight into the processes and mechanisms has potential to identify new therapeutic targets.

Proteomics and pulse azidohomoalanine labeling of newly synthesized proteins: what are the potential applications?

Measuring the immediate changes in cells that arise from changing environmental conditions is crucial to understanding the underlying mechanisms involved. These changes can be measured with metabolic stable isotope fully labeled proteomes, but requires looking for changes in the midst of a large background. In addition, labeling efficiency can be an issue in primary and fully differentiated cells.

Global site-specific analysis of glycoprotein N-glycan processing.

N-glycans contribute to the folding, stability and functions of the proteins they decorate. They are produced by transfer of the glycan precursor to the sequon Asn-X-Thr/Ser, followed by enzymatic trimming to a high-mannose-type core and sequential addition of monosaccharides to generate complex-type and hybrid glycans. This process, mediated by the concerted action of multiple enzymes, produces a mixture of related glycoforms at each glycosite, making analysis of glycosylation difficult.

A SPR aptamer sensor for mercury based on AuNPs@NaYF:Yb,Tm,Gd upconversion luminescent nanoparticles.

A new aptamer-based surface plasmon resonance (SPR) system has been designed to detect Hg that utilizes near-infrared (NIR)-to-NIR gold nanoparticle coated NaYF:Yb,Tm,Gd up-conversion nanoparticles (AuNPs@NaYF:Yb,Tm,Gd UCNPs) as probes. The AuNPs@NaYF:Yb,Tm,Gd UCNPs were prepared and excited by near-infrared light (980 nm) which emitted at a near-infrared wavelength (808 nm) using an inexpensive infrared continuous wave laser diode. The AuNPs@NaYF:Yb,Tm,Gd UCNPs were conjugated with Hg aptamers.

HILAQ: A Novel Strategy for Newly Synthesized Protein Quantification.

Here we describe a new strategy, HILAQ (Heavy Isotope Labeled Azidohomoalanine Quantification), to rapidly quantify the molecular vulnerability profile to oxytosis, which is an oxidative stress-induced programed cell death pathway that has been reported to be involved in aging and neurodegenerative diseases. HILAQ was able to quantify 1962 newly synthesized proteins (NSPs) after 1 h of pulse labeling in HEK293T cell line, while 353 proteins were quantified using the previously published QuaNCAT protocol. HILAQ was successfully applied to the HT22 oxytosis model.

The alteration of H4-K16ac and H3-K27met influences the differentiation of neural stem cells.

The neural stem cell therapy provides a promising future for patients with central nerve system damage, thus an insight into its differentiation mechanism is urgently needed. Herein, we aimed to identify various histone modifications and reveal their impact on the differentiation of neural stem cells (NSCs) toward neurons. Firstly, we labeled primary NSCs using the stable isotope labeling with amino acids in cell culture (SILAC) technique.