Publications by authors named "Richard Lu"

Injury to the depressor labii inferioris (DLI) is a frequent cause of lower lip asymmetry following deep plane facelift and structural neck contouring. This study characterizes the in vivo innervation of the DLI through intraoperative facial nerve mapping during selective facial neurectomy in 20 consecutive patients. In all cases, dual innervation of the DLI was observed: a superficial branch of the marginal mandibular nerve (MMN) supplies the lateral DLI, while an inferomedial cervical branch innervates the medial DLI.

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Define Challenge: Review of applicants to surgery residency is difficult to standardize and is open to bias. In addition, proper assessment and identification can lead to improved retention and performance in residency.

Tool Description: We developed a standardized tool to assess applicants in a holistic manner and stratify them for ranking.

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In vivo conversion of nonneuronal cells into neurons is a proposed strategy to replace neurons lost to CNS injury or disease. Glia-to-neuron trans-differentiation by viral vector-mediated GFAP mini-promoter-driven NeuroD1 remains hotly debated. Developing inducible, lineage-traceable transgenic mice, we find that astrocyte-to-neuron conversion is restricted to a specific time window within the lesion core of injured spinal cord and brain.

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Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), a leading cause of death by an infectious disease globally, has no efficacious vaccine. Antibodies are implicated in M. tuberculosis control, but the mechanisms of action remain poorly understood.

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Purpose: The FLASH effect, defined as normal tissue sparing while maintaining tumor control with ultra-high dose-rate irradiation, has been demonstrated preclinically in different tumors and tissues. Although the biological mechanisms are unclear, there is a need for clinical trials investigating the value of proton FLASH irradiation (pFLASH). The purpose of this study was to establish an expert consensus regarding prerequisites, study design, and endpoints for the next clinical trials exploring the clinical potentials of pFLASH.

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Background: Chromatin remodeler chromodomain helicase DNA-binding protein 8 (CHD8) defines a subtype of autism that is associated with immune disorders. It remains unknown whether CHD8 plays a cell-intrinsic role in immune cells such as regulatory T cells (Tregs) that maintain immune tolerance through suppressing CD4 and CD8 effector T cells.

Methods: Treg-specific conditional CHD8-deficient mice were generated by crossing Chd8 mice with Foxp3 transgenic mice.

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Glioblastoma (GBM) is the most lethal brain cancer, with GBM stem cells (GSCs) driving therapeutic resistance and recurrence. Targeting GSCs offers a promising strategy for preventing tumor relapse and improving outcomes. We identify SUV39H1, a histone-3, lysine-9 methyltransferase, as critical for GSC maintenance and GBM progression.

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Medulloblastoma is the most common malignant pediatric brain cancer and is broadly categorized into four molecular subgroups. Understanding the cell origins of medulloblastoma is crucial for preventing tumor formation and relapse. Recent single-cell transcriptomics studies have identified the potential cell lineage vulnerabilities and mechanisms underpinning malignant transformation in medulloblastoma.

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Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex genetic alterations. The basic-helix-loop-helix (bHLH) transcription factors ASCL1 and OLIG2 are dynamically co-expressed in GBMs; however, their combinatorial roles in regulating the plasticity and heterogeneity of GBM cells are unclear. Here, we show that induction of somatic mutations in subventricular zone (SVZ) progenitor cells leads to the dysregulation of ASCL1 and OLIG2, which then function redundantly and are required for brain tumor formation in a mouse model of GBM.

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the causative agent of tuberculosis (TB), is a leading cause of death by an infectious disease globally, with no efficacious vaccine. Antibodies are implicated in control, but the mechanisms of antibody action remain poorly understood. We assembled a library of TB monoclonal antibodies (mAb) and screened for the ability to restrict in mice, identifying protective antibodies targeting known and novel antigens.

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Article Synopsis
  • - The formation of brain blood vessels starts with invasion from the perineural vascular plexus and involves vessel sprouting and growth, with oligodendrocyte-vascular interaction noted during development.
  • - Oligodendrocyte progenitor cells (OPCs) are crucial for maintaining vessel density in both embryonic and postnatal stages of the neocortex, with their loss resulting in reduced vascular density.
  • - Although OPCs migrate independently of blood vessel proximity, their secretions have been shown to support the growth of vascular endothelial cells, indicating a significant role in influencing vessel density.
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The decreased ability of mature oligodendrocytes to produce myelin negatively affects remyelination in demyelinating diseases and aging, but the underlying mechanisms are incompletely understood. In the present study, we identify a mature oligodendrocyte-enriched transcriptional coregulator diabetes- and obesity-related gene (DOR)/tumor protein p53-inducible nuclear protein 2 (TP53INP2), downregulated in demyelinated lesions of donors with multiple sclerosis and in aged oligodendrocyte-lineage cells. Dor ablation in mice of both sexes results in defective myelinogenesis and remyelination.

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Vanadium dioxide (VO) is an excellent phase transition material widely used in various applications, and thus inevitably enters the environment via different routes and encounters various organisms. Nonetheless, limited information is available on the environmental hazards of VO. In this study, we investigated the impact of two commercial VO particles, nanosized S-VO and micro-sized M-VO on the white rot fungus Phanerochaete chrysosporium.

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Article Synopsis
  • Evidence suggests that antibodies may help control tuberculosis (TB), but the details of how they work and their potential for therapeutic use are not well explored.
  • The researchers created 52 variants of the Fc region of an antibody targeting the Mycobacterium tuberculosis capsule, aiming to enhance its ability to restrict the bacteria.
  • Their findings indicate that some engineered antibodies can effectively engage neutrophils to fight the infection by boosting their survival and antimicrobial activity, highlighting the promise of these antibodies as potential TB treatments.
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Article Synopsis
  • - The study investigates the role of the zinc-finger protein ZFP488 in the development and repair of oligodendrocytes, which are cells responsible for myelination in the central nervous system.
  • - Researchers created a genetically modified mouse to understand ZFP488's role, finding that its absence led to delayed myelination during development and impaired recovery post-injury.
  • - Analysis showed that ZFP488 promotes the expression of genes necessary for myelination, indicating its critical role in regulating the differentiation of oligodendrocytes at various developmental stages.
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Huntington's disease and juvenile-onset schizophrenia have long been regarded as distinct disorders. However, both manifest cell-intrinsic abnormalities in glial differentiation, with resultant astrocytic dysfunction and hypomyelination. To assess whether a common mechanism might underlie the similar glial pathology of these otherwise disparate conditions, we used comparative correlation network approaches to analyse RNA-sequencing data from human glial progenitor cells (hGPCs) produced from disease-derived pluripotent stem cells.

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Article Synopsis
  • Biomolecular condensates are membraneless cell compartments that form through liquid-liquid phase separation (LLPS), playing a crucial role in both normal cellular functions and cancer development.
  • Recent research shows how these condensates influence the Hippo signaling pathway, which is vital for organ development and cancer progression, particularly impacting the YAP and TAZ proteins.
  • The review emphasizes the potential of targeting these condensates in cancer treatment, as they can alter gene expression and promote tumor growth by changing how transcriptional co-activators and chromatin interact.
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Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment.

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Oligodendrocyte differentiation and myelination in the central nervous system are controlled and coordinated by a complex gene regulatory network that contains several transcription factors, including Zfp488 and Nkx2.2. Despite the proven role in oligodendrocyte differentiation little is known about the exact mode of Zfp488 and Nkx2.

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Purpose: Incisional ventral hernias (IVH) are common after laparotomies, with up to 20% incidence in 12 months, increasing up to 60% at 3-5 years. Although Small Bites (SB) is the standard technique for fascial closure in laparotomies, its adoption in the United States is limited, and Large Bites (LB) is still commonly performed. We aim to assess the effectiveness of SB regarding IVH.

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