Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes.

Arrayed CRISPR libraries extend the scope of gene-perturbation screens to non-selectable cell phenotypes. However, library generation requires assembling thousands of vectors expressing single-guide RNAs (sgRNAs). Here, by leveraging massively parallel plasmid-cloning methodology, we show that arrayed libraries can be constructed for the genome-wide ablation (19,936 plasmids) of human protein-coding genes and for their activation and epigenetic silencing (22,442 plasmids), with each plasmid encoding an array of four non-overlapping sgRNAs designed to tolerate most human DNA polymorphisms.

Translational evaluation of metabolic risk factors impacting DBS efficacy for PD-Related sleep and depressive disorders: preclinical, prospective and cohort studies.

Background: Parkinson's disease (PD) is linked with metabolic risk factors including body mass index (BMI), fasting blood glucose (FBG), cholesterol levels, and triglycerides (TG). The extent to which these factors affect motor symptoms, depression, and sleep problems in PD, as well as their role in determining the success of deep brain stimulation (DBS) therapy, is yet to be fully understood.

Methods: This study delved into the effects of metabolic risk factors like BMI, FBG, cholesterol, and TG on the outcomes of DBS in treating PD-related depression and sleep disturbances, across both mouse models and human subjects.

Vaccine-based immunotherapy and related preclinical models for glioma.

Glioma, the most common primary malignant tumor in the central nervous system (CNS), lacks effective treatments, and >60% of cases are glioblastoma (GBM), the most aggressive form. Despite advances in immunotherapy, GBM remains highly resistant. Approaches that target tumor antigens expedite the development of immunotherapies, including personalized tumor-specific vaccines, patient-specific target selection, dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells.

Crystalline Phase Engineering to Modulate the Interfacial Interaction of the Ruthenium/Molybdenum Carbide for Acidic Hydrogen Evolution.

Ruthenium (Ru) is an ideal substitute to commercial Pt/C for the acidic hydrogen evolution reaction (HER), but it still suffers from undesirable activity due to the strong adsorption free energy of H* (Δ). Herein, we propose crystalline phase engineering by loading Ru clusters on precisely prepared cubic and hexagonal molybdenum carbide (α-MoC/β-MoC) supports to modulate the interfacial interactions and achieve high HER activity. Advanced spectroscopies demonstrate that Ru on β-MoC shows a lower valence state and withdraws more electrons from the support than that of Ru on α-MoC, indicative of a strong interfacial interaction.

Sub-2 nm IrRuNiMoCo High-Entropy Alloy with Iridium-Rich Medium-Entropy Oxide Shell to Boost Acidic Oxygen Evolution.

Ensuring high catalytic activity and durability at low iridium (Ir)usage is still a big challenge for the development of electrocatalysts toward oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE). Here, a rapid liquid-reduction combined with surface galvanic replacement strategy is reported to synthesize the sub 2 nm high-entropy alloy (HEA) nanoparticles featured with Ir-rich IrRuNiMo medium-entropy oxide shell (Ir-MEO) and a IrRuCoNiMo HEA core (HEA@Ir-MEO). Advanced spectroscopies reveal that the Ir-rich MEO shell inhibits the severe structural evolution of transition metals upon the OER, thus guaranteeing the structural stability.

LRRK2 Gly2019Ser Mutation Promotes ER Stress via Interacting with THBS1/TGF-β1 in Parkinson's Disease.

The gene mutations of LRRK2, which encodes leucine-rich repeat kinase 2 (LRRK2), are associated with one of the most prevalent monogenic forms of Parkinson's disease (PD). However, the potential effectors of the Gly2019Ser (G2019S) mutation remain unknown. In this study, the authors investigate the effects of LRRK2 G2019S on endoplasmic reticulum (ER) stress in induced pluripotent stem cell (iPSC)-induced dopamine neurons and explore potential therapeutic targets in mice model.

Facial nerve in skullbase tumors: imaging and clinical relevance.

Facial nerve, the 7th cranial nerve, is a mixed nerve composed of sensory and motor fibers, and its main branch is situated in the cerebellopontine angle. Facial nerve dysfunction is a debilitating phenomenon that can occur in skullbase tumors and Bell's pals. Recovery of the facial nerve dysfunction after surgery for skullbase tumors can be disappointing, but is usually favorable in Bell's palsy.

Bioinformatic Analysis of Genetic Factors from Human Blood Samples and Postmortem Brains in Parkinson's Disease.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders characterized by motor and nonmotor symptoms due to the selective loss of midbrain dopaminergic neurons. Pharmacological and surgical interventions have not been possible to cure PD; however, the cause of neurodegeneration remains unclear. Here, we performed and tested a multitiered bioinformatic analysis using the GEO and Proteinexchange database to investigate the gene expression involved in the pathogenesis of PD.

Mechanisms of Autoimmune Cell in DA Neuron Apoptosis of Parkinson's Disease: Recent Advancement.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that manifests as motor and nonmotor symptoms due to the selective loss of midbrain DArgic (DA) neurons. More and more studies have shown that pathological reactions initiated by autoimmune cells play an essential role in the progression of PD. Autoimmune cells exist in the brain parenchyma, cerebrospinal fluid, and meninges; they are considered inducers of neuroinflammation and regulate the immune in the human brain in PD.

The Role of Non-Coding RNAs in the Pathogenesis of Parkinson's Disease: Recent Advancement.

Parkinson's disease (PD) is a prevalent neurodegenerative aging disorder that manifests as motor and non-motor symptoms, and its etiopathogenesis is influenced by non-coding RNAs (ncRNAs). Signal pathway and gene sequence studies have proposed that alteration of ncRNAs is relevant to the occurrence and development of PD. Furthermore, many studies on brain tissues and body fluids from patients with PD indicate that variations in ncRNAs and their target genes could trigger or exacerbate neurodegenerative pathogenesis and serve as potential non-invasive biomarkers of PD.

Genetic Imaging of Neuroinflammation in Parkinson's Disease: Recent Advancements.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative aging disorders characterized by motor and non-motor symptoms due to the selective loss of midbrain dopaminergic (DA) neurons. The decreased viability of DA neurons slowly results in the appearance of motor symptoms such as rigidity, bradykinesia, resting tremor, and postural instability. These symptoms largely depend on DA nigrostriatal denervation.

Therapy of Sporadic and NF2-Related Vestibular Schwannoma.

Vestibular schwannoma (VS) is a benign primary brain tumor that occurs sporadic or as part of a genetic syndrome. The most common cause is the mutation of the NF2 tumor suppressor gene that is involved in the production of the protein merlin. Merlin plays a role in cell growth and cell adhesion.

Downregulated lncRNA-SNHG1 enhances autophagy and prevents cell death through the miR-221/222 /p27/mTOR pathway in Parkinson's disease.

Autophagy has been shown to be critically associated with the central mechanisms underlying Parkinson's disease (PD), while the mechanisms contributing to the imbalance of autophagy remain unclear. Small nucleolar RNA host gene 1 (SNHG1), a well-studied long noncoding RNA, has been reported to be significantly increased in PD. The potential biological functions of SNHG1 in the regulation of neuronal autophagy and cell death in PD, however, have not yet been completely elucidated.

MicroRNA-124 regulates the expression of p62/p38 and promotes autophagy in the inflammatory pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms due to the selective loss of midbrain dopaminergic neurons. The evidence for a chronic inflammatory reaction mediated by microglial cells in the brain is particularly strong in PD. In our previous study, we have shown that brain-specific microRNA-124 (miR-124) is significantly down-regulated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and that it can also inhibit neuroinflammation during the development of PD.

A lincRNA-p21/miR-181 family feedback loop regulates microglial activation during systemic LPS- and MPTP- induced neuroinflammation.

The role of microglial-mediated sustained neuroinflammation in the onset and progression of Parkinson's disease (PD) is well established, but the mechanisms contributing to microglial activation remain unclear. LincRNA-p21, a well studied long intergenic noncoding RNA (lincRNA), plays pivotal roles in diverse biological processes and diseases. Its role in microglial activation and inflammation-induced neurotoxicity, however, has not yet been fully elucidated.

MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis of Parkinson's disease.

Background: Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD.

Overexpression of miR-155 in the liver of transgenic mice alters the expression profiling of hepatic genes associated with lipid metabolism.

Hepatic expression profiling has revealed miRNA changes in liver diseases, while hepatic miR-155 expression was increased in murine non-alcoholic fatty liver disease, suggesting that miR-155 might regulate the biological process of lipid metabolism. To illustrate the effects of miR-155 gain of function in transgenic mouse liver on lipid metabolism, transgenic mice (i.e.