Parkinsonism originates in a discrete secondary and dystonia in a primary motor cortical-basal ganglia subcircuit.

Although manifesting contrasting phenotypes, Parkinson's disease and dystonia, the two most common movement disorders, can originate from similar pathophysiology. Previously, we demonstrated that lesioning (silencing) of a discrete dorsal region in the globus pallidus (rodent equivalent to globus pallidus externa) in rats and produced parkinsonism, while lesioning a nearby ventral hotspot-induced dystonia. Presently, we injected fluorescent-tagged multi-synaptic tracers into these pallidal hotspots (n = 36 Long Evans rats) and permitted 4 days for the viruses to travel along restricted connecting pathways and reach the motor cortex before sacrificing the animals.

CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

Background: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation.

Pseudoaneurysm as a differential for the computed tomography angiography "spot sign" in atypical presentations of intracerebral hemorrhage: illustrative case.

Background: The computed tomography angiography (CTA) "spot sign" is a well-recognized radiographic marker in primary intracerebral hemorrhage (ICH). Although it has been demonstrated to represent an area of active hemorrhage or contrast extravasation, the exact pathophysiology remains unclear. Vascular mimics of the spot sign have been identified; however, those representing pseudoaneurysm and small vessel aneurysm have rarely been reported.

Inhibition of Granulocytic Myeloid-Derived Suppressor Cells Overcomes Resistance to Immune Checkpoint Inhibition in LKB1-Deficient Non-Small Cell Lung Cancer.

LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non-small cell lung cancer (NSCLC). Although treatment of NSCLC with immune checkpoint inhibitors (ICI) has resulted in improved overall survival in a subset of patients, studies have revealed that co-occurring KRAS/LKB1 mutations drive primary resistance to ICIs in NSCLC. Effective therapeutic options that overcome ICI resistance in LKB1-mutant NSCLC are limited.

Novel Kras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden.

Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establish Kras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [Kras (K), KrasTp53(KP), KrasTp53Lkb1 (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU).

Synthesis, Structures, and Water Adsorption of Two Coordination Polymers Constructed by M(II) (M = Ni (1) and Zn (2)) with 1,3-Bis(4-Pyridyl)Propane (bpp) and 1,2,4,5-Benzenetetracarboxylate (BT) Ligands.

Two coordination polymers (CPs), with chemical formulas {[Ni(bpp)(BT)(HO)] 1.5(EtOH) 1.5HO} () and [Zn(bpp)(BT)]·5HO () (bpp = 1,3-bis(4-pyridyl)propane, and BT = tetraanion of 1,2,4,5-Benzenetetracarboxylic acid), have been synthesized and structurally characterized by single-crystal X-ray diffraction methods.

The effectiveness and safety of acupuncture in the treatment of lumbar disc herniation: Protocol for a systematic review and meta-analysis.

Background: Lumbar disc herniation (LDH) is a common disease that seriously affects patients' quality of life. Although several articles have reported that acupuncture can improve the symptoms of LDH, different guidelines do not evaluate the efficacy of acupuncture consistently, new randomized controlled trials have been published in recent years.The purpose of this study is to evaluate the efficacy and safety of acupuncture for LDH.

Author Correction: Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure.