Engineering Anti-CRISPR Proteins to Create CRISPR-Cas Protein Switches for Activatable Genome Editing and Viral Protease Detection.

Proteins capable of switching between distinct active states in response to biochemical cues are ideal for sensing and controlling biological processes. Activatable CRISPR-Cas systems are significant in precise genetic manipulation and sensitive molecular diagnostics, yet directly controlling Cas protein function remains challenging. Herein, we explore anti-CRISPR (Acr) proteins as modules to create synthetic Cas protein switches (CasPSs) based on computational chemistry-directed rational protein interface engineering.

CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy.

Background: Multiple myeloma (MM) is an incurable hematological malignancy of the plasma cells. The maintenance of protein homeostasis is critical for MM cell survival. Elevated levels of paraproteins in MM cells are cleared by proteasomes or lysosomes, which are independent but inter-connected with each other.

A universal orthogonal imaging platform for living-cell RNA detection using fluorogenic RNA aptamers.

MicroRNAs (miRNAs) are crucial regulators of gene expression at the post-transcriptional level, offering valuable insights into disease mechanisms and prospects for targeted therapeutic interventions. Herein, we present a class of miRNA-induced light-up RNA sensors (miLS) that are founded on the toehold mediated principle and employ the fluorogenic RNA aptamers Pepper and Squash as imaging modules. By incorporating a sensor switch to disrupt the stabilizing stem of these aptamers, our design offers enhanced flexibility and convertibility for different target miRNAs and aptamers.

A collagen-immobilized nanodevice for ratiometric imaging of cancer biomarkers in the tumor microenvironment.

Monitoring the spatiotemporal dynamics of cancer biomarkers within the tumor microenvironment (TME) is critical to understanding their roles in tumorigenesis. Here, we reported a multifunctional fusion protein (collagen-binding domain and duck circovirus tag fused to mCherry, CBD-mCherry-DCV) capable of binding collagen with high affinity and covalently binding specific nucleic acids with exceptional efficiency. We then constructed a chimeric protein-nucleic acid nanodevice (CPNN) using CBD-mCherry-DCV and an aptamer-based sensing module to enable spatially controlled ratiometric imaging of cancer biomarkers in the TME.

Striking a growth-defense balance: Stress regulators that function in maize development.

Maize (Zea mays) cultivation is strongly affected by both abiotic and biotic stress, leading to reduced growth and productivity. It has recently become clear that regulators of plant stress responses, including the phytohormones abscisic acid (ABA), ethylene (ET), and jasmonic acid (JA), together with reactive oxygen species (ROS), shape plant growth and development. Beyond their well established functions in stress responses, these molecules play crucial roles in balancing growth and defense, which must be finely tuned to achieve high yields in crops while maintaining some level of defense.

Phosphorescent-Dye-Sensitized Quantum-Dot Light-Emitting Diodes with 37% External Quantum Efficiency.

Exciton harvesting is of paramount importance for quantum-dot light-emitting diodes (QLEDs). Direct exciton harvesting by the quantum dots (QDs) emitting layer suffers from poor hole injection due to the low conduction bands and valence bands of QDs, leading to unbalanced electron-hole injection and recombination. To address this issue, here, an exciton sensitizing approach is reported, where excitons form on a phosphorescent-dye-doped layer, which then transfer their energies to adjacent QDs layer for photon emission.

Exosome miRNAs profiling in serum and prognostic evaluation in patients with multiple myeloma.

MicroRNAs (MiRNAs) carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment. Our study aimed at identifying the expression profile of exosomal miRNAs (exo-miRNAs) in the serum of multiple myeloma (MM) patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis. Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing.

Programmable Proteolysis-Activated Transcription for Highly Sensitive Ratiometric Electrochemical Detection of Viral Protease.

Viral proteases play a crucial role in viral infection and are regarded as promising targets for antiviral drug development. Consequently, biosensing methods that target viral proteases have contributed to the study of virus-related diseases. This work presents a ratiometric electrochemical sensor that enables highly sensitive detection of viral proteases through the integration of target proteolysis-activated in vitro transcription and the DNA-functionalized electrochemical interface.

Husband-wife Relationship, Neonatal Health, Breast Milk Volume and Postpartum Depression: A Prospective Cohort Study.

Postpartum depression (PPD) is a major public health problem that has negative effects on mothers, infants, and society. This study was aimed at investigating the prevalence of PPD and elucidating the delivery factors implicated in PPD so as take more targeted measures for reducing the potential risk factors. A prospective cohort study was conducted.

Maize LOST SUBSIDIARY CELL encoding a large subunit of ribonucleotide reductase is required for subsidiary cell development and plant growth.

The four-celled stomatal complex consists of a pair of guard cells (GCs) and two subsidiary cells (SCs) in grasses, which supports a fast adjustment of stomatal aperture. The formation and development of SCs are thus important for stomatal functionality. Here, we report a maize lost subsidiary cells (lsc) mutant, with many stomata lacking one or two SCs.

Resveratrol alleviates postpartum depression-like behavior by activating autophagy via SIRT1 and inhibiting AKT/mTOR pathway.

Background: Postpartum depression (PPD) causes maternal mortality, and has a high disability rate. In recent years, studies have suggested the Sirt1 gene to be involved in the pathogenesis of depression. Resveratrol (RSV), an activator of Sirt1, has been investigated in depressive behavior.

Kinetics Accelerated CRISPR-Cas12a Enabling Live-Cell Monitoring of Mn Homeostasis.

The CRISPR/Cas12a system has been repurposed as a versatile nuclei acid bio-imaging tool, but its utility in sensing non-nucleic acid analytes in living cells has been less exploited. Herein, we demonstrated the ability of Mn to accelerate cleavage kinetics of Cas12a and deployed for live-cell Mn sensing by leveraging the accelerated trans-cleavage for signal reporting. In this work, we found that Mn could significantly boost both the cis-cleavage and trans-cleavage activities of Cas12a.

PAM-less conditional DNA substrates leverage trans-cleavage of CRISPR-Cas12a for versatile live-cell biosensing.

The CRISPR-Cas system has been repurposed as a powerful live-cell imaging tool, but its utility is limited to genomic loci and mRNA imaging in living cells. Here, we demonstrated the potential of the CRISPR-Cas system as a generalizable live-cell biosensing tool by extending its applicability to monitor diverse intracellular biomolecules. In this work, we engineered a CRISPR-Cas12a system with a generalized stimulus-responsive switch mechanism based on PAM-less conditional DNA substrates (pcDNAs).

Amplified and label-free electrochemical detection of a protease biomarker by integrating proteolysis-triggered transcription.

Cell-free synthetic biology provides a promising strategy for developing high-performance biosensors by integrating with advanced testing technologies. However, the combination of synthetic biology with electrochemical testing techniques is still underdeveloped. Here, we proposed an electrochemical biosensor for the label-free and ultrasensitive detection of target protease biomarker by coupling a protease-responsive RNA polymerase (PR) for signal amplification.

The association of oxytocin with major depressive disorder: role of confounding effects of antidepressants.

Major depressive disorder is a genetic susceptible disease, and a psychiatric syndrome with a high rate of incidence and recurrence. Because of its complexity concerning etiology and pathogenesis, the cure rate of first-line antidepressants is low. In recent years, accumulative evidences revealed that oxytocin act as a physiological or pathological participant in a variety of complex neuropsychological activities, including major depressive disorder.

A CRISPR-Cas autocatalysis-driven feedback amplification network for supersensitive DNA diagnostics.

Artificial nucleic acid circuits with precisely controllable dynamic and function have shown great promise in biosensing, but their utility in molecular diagnostics is still restrained by the inability to process genomic DNA directly and moderate sensitivity. To address this limitation, we present a CRISPR-Cas-powered catalytic nucleic acid circuit, namely, CRISPR-Cas-only amplification network (CONAN), for isothermally amplified detection of genomic DNA. By integrating the stringent target recognition, helicase activity, and trans-cleavage activity of Cas12a, a Cas12a autocatalysis-driven artificial reaction network is programmed to construct a positive feedback circuit with exponential dynamic in CONAN.

A Missense Mutation in a Large Subunit of Ribonucleotide Reductase Confers Temperature-Gated Tassel Formation.

Temperature is a major factor regulating plant growth. To reproduce at extreme temperatures, plants must develop normal reproductive organs when exposed to temperature changes. However, little is known about the underlying molecular mechanisms.

Optimized integration of fluoxetine and 7, 8-dihydroxyflavone as an efficient therapy for reversing depressive-like behavior in mice during the perimenopausal period.

Fluoxetine (FLX) has been considered as an effective anti-depressant drug. Besides, previous studies reported reasonable anti-depressant effects for 7, 8-dihydroxyflavone (7, 8 DHF). However, the combination of FLX and 7, 8 DHF in a well-established depression model has not been explored.

Target-activated transcription for the amplified sensing of protease biomarkers.

Signal amplification is an effective way to achieve sensitive analysis of biomarkers, exhibiting great promise in biomedical research and clinical diagnosis. Inspired by the transcription process, here we present a versatile strategy that enables effective amplification of proteolysis into nucleic acid signal outputs in a homogeneous system. In this strategy, a protease-activatable T7 RNA polymerase is engineered as the signal amplifier and achieves 3 orders of magnitude amplification in signal gain.

Engineering Cell-Surface Receptors with DNA Nanotechnology for Cell Manipulation.

Cell-surface receptors play pivotal roles in the regulation of cell fate. Molecular engineering of cell-surface receptors enables control of cell signaling and manipulation of cell behavior in a user-defined way. Currently, the development of chemical-biological approaches for non-genetic engineering and regulation of membrane receptors is attracting significant interest.

Engineering of Nucleic Acids and Synthetic Cofactors as Holo Sensors for Probing Signaling Molecules in the Cellular Membrane Microenvironment.

The comprehensive understanding of the mechanisms underlying the interaction of cells with their membrane microenvironment is of great value for fundamental biological research; however, tracking biomolecules on cell surfaces with high temporal and spatial resolution remains a challenge. Herein, a modular strategy is presented for the construction of cell surface DNA-based sensors by engineering DNA motifs and synthetic cofactors. In this strategy, a stimuli-reactive organic molecule is employed as the cofactor for the DNA motif, and the self-assembly of them forms a FRET-based holo DNA-based sensor.

[Design of a long-distance consultation system using wireless sensor networks].

A remote interactive consultation system based on wireless sensor networks is proposed for family health care works and non-hospital special case patient monitoring. The sensor nodes are integrated into a local area network to collect a variety of human physiological information, which is uploaded to Internet through the Code-Division Multiple Access (CDMA) wireless network technology and sent to the database based on GIS spatial location query technology for achieving electronic diagnosis. Users or administrators can visit remote monitor region through Internet.