Deep Brain Stimulation for Parkinson's Disease During the COVID-19 Pandemic: Patient Perspective.

Background: Public health guidelines have recommended that elective medical procedures, including deep brain stimulation (DBS) surgery for Parkinson's disease (PD), should not be scheduled during the coronavirus (COVID-19) pandemic to prevent further virus spread and overload on health care systems. However, delaying DBS surgery for PD may not be in the best interest of individual patients and is not called for in regions where virus spread is under control and inpatient facilities are not overloaded.

Methods: We administered a newly developed phone questionnaire to 20 consecutive patients with PD who received DBS surgery in Ruijin Hospital in Shanghai during the COVID-19 pandemic.

Male pheromones modulate synaptic transmission at the neuromuscular junction in a sexually dimorphic manner.

The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The synaptic transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of synaptic transmission remains poorly understood.

A protocol for simultaneous Ca and morphology imaging of brain endothelial tip cells in larval zebrafish.

Endothelial tip cells (ETCs) located at growing blood vessels display high morphological dynamics and associated intracellular Ca activities with different spatiotemporal patterns during migration. Examining the Ca activity and morphological dynamics of ETCs will provide an insight for understanding the mechanism of vascular development in organs, including the brain. Here, we describe a method for simultaneous monitoring and relevant analysis of the Ca activity and morphology of growing brain ETCs in larval zebrafish.

c-CSN: Single-cell RNA Sequencing Data Analysis by Conditional Cell-specific Network.

The rapid advancement of single-cell technologies has shed new light on the complex mechanisms of cellular heterogeneity. However, compared to bulk RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq) suffers from higher noise and lower coverage, which brings new computational difficulties. Based on statistical independence, cell-specific network (CSN) is able to quantify the overall associations between genes for each cell, yet suffering from a problem of overestimation related to indirect effects.

In Situ Regulation of Macrophage Polarization to Enhance Osseointegration Under Diabetic Conditions Using Injectable Silk/Sitagliptin Gel Scaffolds.

As a chronic inflammatory disease, diabetes mellitus creates a proinflammatory microenvironment around implants, resulting in a high rate of implant loosening or failure in osteological therapies. In this study, macroporous silk gel scaffolds are injected at the bone-implant interface for in situ release of sitagliptin that can regulate macrophage response to create a prohealing microenvironment in diabetes mellitus disease. Notably, it is discovered that sitagliptin induces macrophage polarization to the M2 phenotype and alleviates the impaired behaviors of osteoblasts on titanium (Ti) implants under diabetic conditions in a dose-dependent manner.

Endogenous promoter-driven sgRNA for monitoring the expression of low-abundance transcripts and lncRNAs.

Detection of endogenous signals and precise control of genetic circuits in the natural context are essential to understand biological processes. However, the tools to process endogenous information are limited. Here we developed a generalizable endogenous transcription-gated switch that releases single-guide RNAs in the presence of an endogenous promoter.

Distinguishing Glioblastoma Subtypes by Methylation Signatures.

Glioblastoma, also called glioblastoma multiform (GBM), is the most aggressive cancer that initiates within the brain. GBM is produced in the central nervous system. Cancer cells in GBM are similar to stem cells.

Prediction and Validation of Mouse Meiosis-Essential Genes Based on Spermatogenesis Proteome Dynamics.

The molecular mechanism associated with mammalian meiosis has yet to be fully explored, and one of the main reasons for this lack of exploration is that some meiosis-essential genes are still unknown. The profiling of gene expression during spermatogenesis has been performed in previous studies, yet few studies have aimed to find new functional genes. Since there is a huge gap between the number of genes that are able to be quantified and the number of genes that can be characterized by phenotype screening in one assay, an efficient method to rank quantified genes according to phenotypic relevance is of great importance.

A Cas-embedding strategy for minimizing off-target effects of DNA base editors.

DNA base editors, typically comprising editing enzymes fused to the N-terminus of nCas9, display off-target effects on DNA and/or RNA, which have remained an obstacle to their clinical applications. Off-target edits are typically countered via rationally designed point mutations, but the approach is tedious and not always effective. Here, we report that the off-target effects of both A > G and C > T editors can be dramatically reduced without compromising the on-target editing simply by inserting the editing enzymes into the middle of nCas9 at tolerant sites identified using a transposon-based genetic screen.

Biomimicking Antibacterial Opto-Electro Sensing Sutures Made of Regenerated Silk Proteins.

Surgical sutures play an important role across a wide range of medical treatments and a wide variety exist, differing in strength, size, composition, and performance. Recently, increasing interest has been paid to bioactive and electronic sutures made of synthetic polymers, owing to their ability to reduce inflammation as well as medically and/or electronically facilitate wound healing. However, integrating sensing capabilities into bioactive sutures without adversely affecting their mechanical strength, biocompatibility, and/or bioactivity remains challenging.

Programmable C-to-U RNA editing using the human APOBEC3A deaminase.

Programmable RNA cytidine deamination has recently been achieved using a bifunctional editor (RESCUE-S) capable of deaminating both adenine and cysteine. Here, we report the development of "CURE", the first cytidine-specific C-to-U RNA Editor. CURE comprises the cytidine deaminase enzyme APOBEC3A fused to dCas13 and acts in conjunction with unconventional guide RNAs (gRNAs) designed to induce loops at the target sites.

Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a.

Acid-sensing ion channels (ASICs), the main H receptors in the central nervous system, sense extracellular pH fluctuations and mediate cation influx. ASIC1a, the major subunit responsible for acid-activated current, is widely expressed in brain neurons, where it plays pivotal roles in diverse functions including synaptic transmission and plasticity. However, the underlying molecular mechanisms for these functions remain mysterious.

ADSCs-derived extracellular vesicles alleviate neuronal damage, promote neurogenesis and rescue memory loss in mice with Alzheimer's disease.

Despite the various mechanisms that involved in the pathogenesis of Alzheimer's disease (AD), neuronal damage and synaptic dysfunction are the key events leading to cognition impairment. Therefore, neuroprotection and neurogenesis would provide essential alternatives to the rescue of AD cognitive function. Here we demonstrated that extracellular vesicles secreted from adipose-derived mesenchymal stem cells (ADSCs-derived EVs, abbreviated as EVs) entered the brain quickly and efficiently following intranasal administration, and majorly accumulated in neurons within the central nervous system (CNS).

Identifying the RNA signatures of coronary artery disease from combined lncRNA and mRNA expression profiles.

Coronary artery disease (CAD) is the most common cardiovascular disease. CAD research has greatly progressed during the past decade. mRNA is a traditional and popular pipeline to investigate various disease, including CAD.

Piezo1-Mediated Ca Activities Regulate Brain Vascular Pathfinding during Development.

During development, endothelial tip cells (ETCs) located at the leading edge of growing vascular plexus guide angiogenic sprouts to target vessels, and thus, ETC pathfinding is fundamental for vascular pattern formation in organs, including the brain. However, mechanisms of ETC pathfinding remain largely unknown. Here, we report that Piezo1-mediated Ca activities at primary branches of ETCs regulate branch dynamics to accomplish ETC pathfinding during zebrafish brain vascular development.

GOTI, a method to identify genome-wide off-target effects of genome editing in mouse embryos.

Genome editing holds great potential for correcting pathogenic mutations. We developed a method called GOTI (genome-wide off-target analysis by two-cell embryo injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. GOTI directly compares edited and non-edited cells without the interference of genetic background and thus could detect potential off-target variants with high sensitivity.

A rewritable optical storage medium of silk proteins using near-field nano-optics.

Nanoscale lithography and information storage in biocompatible materials offer possibilities for applications such as bioelectronics and degradable electronics for which traditional semiconductor fabrication techniques cannot be used. Silk fibroin, a natural protein renowned for its strength and biocompatibility, has been widely studied in this context. Here, we present the use of silk film as a biofunctional medium for nanolithography and data storage.

CRISPR/Cas: a potential gene-editing tool in the nervous system.

The rapidly developmental RNA-guided CRISPR/Cas system is a powerful tool for RNA and DNA editing in a variety of cells from different species and makes a great contribution to gene function research, disease model generation and gene therapy development in the past few years. The ease of use, low cost and high efficiency of CRISPR/Cas make it commonly used in various conditions. In this review, we introduce the CRISPR/Cas system and its diverse applications in nervous system briefly, which provides a better understanding for its potential application values.

Photoinduced Tunable and Reconfigurable Electronic and Photonic Devices Using a Silk-Based Diffractive Optics Platform.

A remarkable feature of modern electronic and photonic devices is the ability to maintain their geometric and physical properties in various circumstances for practical applications. However, there is an increasing demand for reconfigurable devices and systems that can be triggered or switched by external stimuli to change geometric, physical, and/or biochemical properties to meet specific requirements such as compact, lightweight, energy-efficient, and tunable features. Here, a set of phototunable and photoreconfigurable electronic and photonic devices composed of reconfigurable arithmetic circuits and programmable coding metamaterials at terahertz frequencies, empowered by a diffractive optics platform using naturally extracted silk proteins, is reported.

Body-Integrated, Enzyme-Triggered Degradable, Silk-Based Mechanical Sensors for Customized Health/Fitness Monitoring and In Situ Treatment.

Mechanical signals such as pressure and strain reflect important psychological and physiological states of the human body. Body-integrated sensors, including skin-mounted and surgically implanted ones, allow personalized health monitoring for the general population as well as patients. However, the development of such measuring devices has been hindered by the strict requirements for human-biocompatible materials and the need for high performance sensors; most existing devices or sensors do not meet all the desired specifications.

Imaging microstructure with diffusion and susceptibility MR: neuronal density correlation in Disrupted-in-Schizophrenia-1 mutant mice.

Purpose: To probe cerebral microstructural abnormalities and assess changes of neuronal density in Disrupted-in-Schizophrenia-1 (DISC1) mice using non-Gaussian diffusion and quantitative susceptibility mapping (QSM).

Materials And Methods: Brain specimens of transgenic DISC1 mice (n = 8) and control mice (n = 7) were scanned. Metrics of neurite orientation dispersion and density imaging (NODDI) and diffusion kurtosis imaging (DKI), as well as QSM, were acquired.

All-Aqueous-Processed Injectable In Situ Forming Macroporous Silk Gel Scaffolds for Minimally Invasive Intracranial and Osteological Therapies.

Hydrogels are widely utilized in regenerative medicine for drug delivery and tissue repair due to their superior biocompatibility and high similarity to the extracellular matrix. For minimally invasive therapies, in situ forming gel scaffolds are desirable, but technical challenges remain to be overcome to achieve the balance between tissue-like strength and cell-sized porosity, especially for intracranial and osteological therapies. Here, a new method-inspired by the liquid crystalline spinning process in natural silk fibers-is reported for preparing injectable silk gel scaffolds with favorable preclinical efficacy and unique characteristics including 1) in situ gelling for minimally invasive surgeries, 2) controllable porosity for efficient cellular infiltration and desirable degradation, 3) resilient and tunable mechanical properties that are compatible with the modulus regime of native soft tissues, and 4) all-aqueous processing that avoids toxic solvents and enables facile loading of bioactive agents.

Discriminating Origin Tissues of Tumor Cell Lines by Methylation Signatures and Dys-Methylated Rules.

DNA methylation is an essential epigenetic modification for multiple biological processes. DNA methylation in mammals acts as an epigenetic mark of transcriptional repression. Aberrant levels of DNA methylation can be observed in various types of tumor cells.