Brain Mechanisms of Fear Reduction Underlying Habituation to Pain in Humans.

Habituation to painful stimuli reflects an endogenous pain alleviation mechanism, and reduced pain habituation has been demonstrated in many chronic pain conditions. In ethology, animals exhibit reduced fear responses while habituating to repeated threatening stimuli. It remains unclear whether pain habituation in humans involves a fear reduction mechanism.

Development of a tumor-region-selective activation monoclonal antibody targeting the 4-1BB receptor for enhanced therapeutic efficacy and safety.

4-1BB is a co-stimulatory immune checkpoint receptor that triggers CD8 T cell activation, leading to robust anti-tumor responses. Although antibodies targeting 4-1BB show promise in preclinical studies, systemic 4-1BB over-activation can cause severe hepatotoxicity, limiting their clinical use. In this study, we developed Pro-Urelumab, an engineered version of the clinical anti-4-1BB antibody (Urelumab), utilizing an autologous hinge as a spatial hindrance-based antibody lock, linked the antibody and antibody lock with a matrix metalloproteinase-2/9 (MMP-2/9) substrate.

A Dual-Structured Chromogenic Enzyme Platform for a Rapid, Sensitive, Durable, and Precise Gene Expression Analysis.

The dual luciferase reporter (DLR) assay is a well-known tool for gene expression analysis. Its ability to provide batch-to-batch, side-by-side normalization makes it a valuable method through which to explore actual sample signals. DLRs identify a real signal based on the stimulant's efficacy and can reflect the slightest change in downstream signaling with its unique signal adjustment ability.

Mid-infrared surface plasmon resonance fiber optic sensors.

We propose and experimentally demonstrate what we believe to be the first mid-infrared surface plasmon resonance (SPR) fiber optic sensor using a D-shaped multimode silica optical fiber coated with a 105 nm indium tin oxide (ITO) layer. The sensor shows resonance around 2700 nm, with a refractive index sensitivity of 1065.70 nm per refractive index unit (nm/RIU) for refractive indices ranging from 1.

Prediction and stratification for the surgical adverse events after minimally invasive esophagectomy: A two-center retrospective study.

Background: Minimally invasive esophagectomy (MIE) is a widely accepted treatment for esophageal cancer, yet it is associated with a significant risk of surgical adverse events (SAEs), which can compromise patient recovery and long-term survival. Accurate preoperative identification of high-risk patients is critical for improving outcomes.

Aim: To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with MIE.

Prognostic nomogram for overall survival of elderly esophageal cancer patients receiving neoadjuvant therapy: a population-based analysis.

Background: As the population of elderly patients with esophageal cancer (EC) increases, it becomes more important to understand the prognostic factors. The aim of the present study is to identify prognostic factors among elderly (>60 years) patients with EC receiving neoadjuvant therapy.

Methods: Patients with EC (>60 years) receiving neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included and divided into a training group and a validation group.

Indole and Coumarin Derivatives Targeting EEF2K in Aβ Folding Reporter Cells.

Misfolding and accumulation of amyloid-β (Aβ) in the brains of patients with Alzheimer's disease (AD) lead to neuronal loss through various mechanisms, including the downregulation of eukaryotic elongation factor 2 (EEF2) protein synthesis signaling. This study investigated the neuroprotective effects of indole and coumarin derivatives on Aβ folding and EEF2 signaling using SH-SY5Y cells expressing Aβ-green fluorescent protein (GFP) folding reporter. Among the tested compounds, two indole (NC009-1, -6) and two coumarin (LM-021, -036) derivatives effectively reduced Aβ misfolding and associated reactive oxygen species (ROS) production.

pH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma.

The blood-brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engager) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB.

Striatal-cortical dysconnectivity underlies somatosensory deficits in Parkinson's disease: Insights from rhythmic auditory-motor training.

Evidence indicates that neurodegenerative diseases spread through distinct brain networks. For Parkinson's disease (PD), somatosensory abnormalities may accompany motor dysfunction in early disease stages when dopaminergic degeneration is limited to the basal ganglia. It remains unclear whether, based on the network-spread account, these abnormalities emanated from aberrant functional connectivity with the basal ganglia, and whether interventions normalizing this connectivity could reverse these abnormalities.

Homoplantaginin Antagonizes -Methyl-d-aspartate Receptor and Extracellular Signal-Regulated Kinase Signaling in Aβ Oligomers-Induced Neuropathology/Toxicity.

Extracts from plants/herbals are great resources of drugs and nutrients. Baicalein, a component present in , was previously found to alleviate the abnormal depolarization brought about by Aβ oligomers. We extended this promising outcome by screening baicalein derivatives, and a natural compound named homoplantaginin was pinpointed.

Coumarin-chalcone derivatives as dual NLRP1 and NLRP3 inflammasome inhibitors targeting oxidative stress and inflammation in neurotoxin-induced HMC3 and BE(2)-M17 cell models of Parkinson's disease.

Background: In Parkinson's disease (PD) brains, microglia are activated to release inflammatory factors to induce the production of reactive oxygen species (ROS) in neuron, and vice versa. Moreover, neuroinflammation and its synergistic interaction with oxidative stress contribute to the pathogenesis of PD.

Methods: In this study, we investigated whether in-house synthetic coumarin-chalcone derivatives protect human microglia HMC3 and neuroblastoma BE(2)-M17 cells against 1-methyl-4-phenyl pyridinium (MPP)-induced neuroinflammation and associated neuronal damage.

Small Molecules Inducing Autophagic Degradation of Expanded Polyglutamine Protein through Interaction with Both Mutant ATXN3 and LC3.

Polyglutamine (polyQ)-mediated spinocerebellar ataxia (SCA), including SCA1, 2, 3, 6, 7, and 17, are caused by mutant genes with expanded CAG repeats, leading to the intracellular accumulation of aggregated proteins, the production of reactive oxygen species, and cell death. Among SCA, SCA3 is caused by a mutation in the ATXN3 (ataxin-3) gene. In a circumstance of polyQ aggregation, the autophagic pathway is induced to degrade the aggregated proteins, thereby suppressing downstream deleterious effects and promoting neuronal survival.

PARylation of 14-3-3 proteins controls the virulence of Magnaporthe oryzae.

Magnaporthe oryzae is a devastating fungal pathogen that causes the rice blast disease worldwide. The post-translational modification of ADP-ribosylation holds significant importance in various fundamental biological processes. However, the specific function of this modification in M.

Diversity-oriented synthesis of chromone inden-1-one-fused cyclopentadienylides and -acylated chromone adducts allylic phosphorus ylides.

An organophosphine-controlled diversity-oriented synthesis of chromone inden-1-one-fused cyclopentadienylides and -acylated 2-((chromone-3-yl)methylene)-indandiones is reported. Key attributes of the methodology are the generation of an allylic P-ylide and subsequent regio- and chemoselective intramolecular cyclization reactions that preferentially result in the aforementioned chromone adducts.

The antagonistic role of an E3 ligase pair in regulating plant NLR-mediated autoimmunity and fungal pathogen resistance.

Plant immune homeostasis is achieved through a balanced immune activation and suppression, enabling effective defense while averting autoimmunity. In Arabidopsis, disrupting a mitogen-activated protein (MAP) kinase cascade triggers nucleotide-binding leucine-rich-repeat (NLR) SUPPRESSOR OF mkk1/2 2 (SUMM2)-mediated autoimmunity. Through an RNAi screen, we identify PUB5, a putative plant U-box E3 ligase, as a critical regulator of SUMM2-mediated autoimmunity.

Hierarchical global and local auxin signals coordinate cellular interdigitation in .

The development of multicellular tissues requires both local and global coordination of cell polarization, however, the mechanisms underlying their interplay are poorly understood. In Arabidopsis, leaf epidermal pavement cells (PC) develop a puzzle-piece shape locally coordinated through apoplastic auxin signaling. Here we show auxin also globally coordinates interdigitation by activating the TIR1/AFB-dependent nuclear signaling pathway.

Creep and Shrinkage Properties of Nano-SiO-Modified Recycled Aggregate Concrete.

The poor performance of recycled concrete aggregate (RCA) leads to greater creep in recycled aggregate concrete (RAC) compared to natural aggregate concrete (NAC). To enhance the quality of RCA, this paper utilizes a 2% concentration of a nano-SiO (NS) solution for pre-soaking RCA. This study aims to replace natural aggregate (NA) with NS-modified recycled aggregate (SRCA) and investigate the creep and shrinkage properties of NS-modified recycled aggregate concrete (SRAC) at various SRCA replacement rates.

Cyclic Behavior and Stress-Strain Model of Nano-SiO-Modified Recycled Aggregate Concrete.

Recycled aggregate concrete (RAC) possesses different mechanical properties than ordinary concrete because of inherent faults in recycled aggregates (RAs), such as the old interfacial transition zone (ITZ). However, the application of nano-SiO presents an effective methodology to enhance the quality of RA. In this study, nano-SiO-modified recycled aggregate (SRA) was used to replace natural aggregate (NA), and the stress-strain relationships and cyclic behavior of nano-SiO-modified recycled aggregate concrete (SRAC) with different SRA replacement rates were investigated.

Investigating the therapeutic effects of novel compounds targeting inflammatory IL-1β and IL-6 signaling pathways in spinocerebellar ataxia type 3.

At least seven dominantly inherited spinocerebellar ataxias (SCA) are caused by expansions of polyglutamine (polyQ)-encoding CAG repeat. The misfolded and aggregated polyQ-expanded proteins increase reactive oxygen species (ROS), cellular toxicity, and neuroinflammation in the disease pathogenesis. In this study, we evaluated the anti-inflammatory potentials of coumarin derivatives LM-021, LMDS-1, LMDS-2, and pharmacological chaperone tafamidis using mouse BV-2 microglia and SCA3 ataxin-3 (ATXN3)/Q-GFP SH-SY5Y cells.

Cadherin-responsive hydrogel combined with dental pulp stem cells and fibroblast growth factor 21 promotes diabetic scald repair via regulating epithelial-mesenchymal transition and necroptosis.

Diabetes causes a loss of sensation in the skin, so diabetics are prone to burns when using heating devices. Diabetic scalded skin is often difficult to heal due to the microenvironment of high glucose, high oxidation, and low blood perfusion. The treatment of diabetic scald mainly focuses on three aspects: 1) promote the formation of the epithelium; 2) promote angiogenesis; and 3) maintain intracellular homeostasis.