Biology subjects

HE, Y.

Publications and source records attributed to HE, Y..

8 recordsLinked to original sources

bioRxiv2026

A brain-tumour axis links chronic stress to gastric cancer progression through NPY signalling

Chronic stress promotes gastric tumour growth, but the central neural pathways remain largely enigmatic. Here, we identify a brain-tumour axis, implicating the central amygdala (CeA) activity in promoting gastric cancer growth through sympathetic neuropeptide Y (NPY) signalling occurring within the tumour. Using clinical datasets, patient samples, pathway tracing, electrophysiology and chemogenetic manipulation, we demonstrate that stress selectively increases NPY Y1 receptor (NPY1R) synthesis in the patients gastric cancer tissue; moreover, the NPY1R density correlates with advanced cancer stage and poor prognosis. In mice, daily constraint chronic stress enhances CeA excitability and promotes sympathetic neurotransmitter norepinephrine release within the tumour microenvironment. Norepinephrine, in turn, increases tumour endogenous NPY/NPY1R production and the activation of downstream MAPK/Erk1/2 signalling pathway, which drives cancer cell proliferation and invasion. Manipulating CeA neuronal activity alone can regulate tumour growth, whereas selectively blocking tumour NPY1R prevents stress-induced tumour progression in vivo and cancer cell migration in vitro. This study identifies a central-to-peripheral circuit linking chronic stress to gastric cancer growth, and highlights NPY1R as a potential therapeutic target.

Cancer Biology↗

bioRxiv2026

A unified law for inhibitory control in active dendrites

Neuronal computation depends on the balance between excitation and inhibition, yet how this balance is implemented across the dendritic tree remains unclear. Classical views predict that inhibition should be most effective near the soma or along the path from excitation to output, but many interneuron subtypes preferentially target remote dendritic compartments. This apparent paradox is sharpened by active dendrites, where local NMDA spikes, calcium plateaus and backpropagating action potentials can make distal branches powerful contributors to somatic firing. Here we develop an analytical framework that extracts general principles of inhibition from biophysically detailed multi-compartment simulations. By reformulating the implicit voltage update of detailed neuron models as a matrix recursion, we derive exact voltage sensitivities to inhibitory synaptic perturbations. This leads to a unified {Phi}-a law: the somatic impact of inhibition factorizes into a global dendritic susceptibility term and a local synaptic perturbation term. Using this law to map inhibitory leverage and identify optimal inhibitory interventions, we show that active dendritic excitation can shift inhibitory hot zones from perisomatic regions toward distal or intermediate compartments. Across neocortical, hippocampal and striatal neuron models, the same response law explains convergent inhibitory strategies despite distinct cellular mechanisms. Our framework turns detailed numerical simulation into analytical theory, providing a general principle for how diverse dendritic inhibition controls active neurons.

neuroscience↗

bioRxiv2026

Optical Windows for Transcranial Brain Imaging in Living Mice: Skull Thinning, Clearing, and Beyond

Longitudinal, noninvasive in vivo imaging is essential for studying brain physiology and pathological mechanisms. Advances in transcranial optical windows, including thinned-skull and optical clearing techniques, have markedly improved imaging depth and resolution when combined with multiphoton microscopy. However, their optical performance often deteriorates rapidly, and quantitative studies on long-term stability and the causes of image quality loss remain limited. In this work, we systematically investigated current transcranial window approaches using multiphoton excited fluorescence microscopy (MPEFM) and adaptive optics, examining longevity, optical aberrations, and imaging resolution. Our results reveal that progressive skull regrowth is a fundamental limitation across all window types, leading to substantial declines in signal quality and resolution for conventional MPEFM thereby reducing achievable high-resolution imaging depth. To address these challenges, we developed a localized glucocorticoid (GC) delivery strategy that significantly extends window performance for up to one month. Furthermore, we demonstrated that a GC-loaded hydrogel sealing method effectively suppressed skull regrowth while preserving optimal optical properties, offering a potential and practical route to chronic, high-fidelity transcranial imaging. These findings provide mechanistic insight into window degradation and establish a framework for sustained, long-term in vivo brain imaging.

neuroscience↗

bioRxiv2025

Dynamic Retinal Pathology in Glaucoma Progression Revealed by High-Resolution Functional Imaging in Vivo

Glaucoma, a complex and multifactorial neurodegenerative disease, is commonly associated with elevated intraocular pressure and primarily characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Despite its prevalence, our understanding and treatment of this disease remain challenging due to the intricate interplay of various pathophysiological factors and the limited capability for in vivo functional study of the disease. In this work, we investigated the dynamic retinal pathology of glaucoma from onset to late stages through longitudinal in vivo high-resolution imaging in a silicone oil-induced ocular hypertension glaucoma mouse model. We developed an optimized adaptive optics two-photon excitation fluorescence microscopy (AO-TPEFM) technique for both morphological and functional assessments of pathological changes in the retina across three distinct glaucoma phenotypes with varying progression rates. Our AO-TPEFM technology visualized the complete process of functional and structural changes in the three most important retinal components related to glaucoma: microvascular vessels, microglia, and RGCs during disease progression. Notably, our functional imaging revealed pathological alterations in microvascular circulation, microglia state, and RGC functionalities at a very early stage of disease development when retinal morphology still appeared normal, providing critical insights into glaucoma pathogenesis. This research also demonstrates that AO-TPEFM is a powerful tool for the in vivo study of general retinal diseases.

bioengineering↗

bioRxiv2025

Toward Crosstalk-free All-optical Interrogation of Neural Circuits

All-optical interrogation, based on high-resolution two-photon stimulation and imaging, has emerged as a potentially transformative approach in neuroscience, allowing for the simultaneous precise manipulation and monitoring of neuronal activity across various model organisms. However, the unintended excitation of light-gated ion channels such as channelrhodopsin (ChR) during two-photon calcium imaging with genetically encoded calcium indicators (GECIs) introduces artifactual neuronal perturbation and contaminates neural activity measurements. In this study, we propose an active pixel power control (APPC) approach, which dynamically adjusts the imaging laser power at each scanning pixel, to address the challenge. We aim to achieve simultaneous two-photon optogenetic manipulation and calcium imaging with a single femtosecond laser, while minimizing the crosstalk between manipulation and imaging. To study this technologys capabilities, we applied it to the larval zebrafish brain in vivo. Our results demonstrate that the APPC approach preserves GECI signal quality while suppressing optogenetic artifacts significantly. This enhances the accuracy of neural circuit dissection and advances the precision of all-optical interrogation, offering a robust framework for probing neural circuit dynamics and causality in vivo with high fidelity, potentially across various model organisms. Importantly, this technology can be seamlessly integrated with commonly used two-photon microscope systems in laboratories worldwide.

neuroscience↗

bioRxiv2025

Rapid adaptive optics enabling near noninvasive high-resolution brain imaging in awake behaving mice

High-resolution imaging under physiological conditions is essential for studying biological mechanisms and disease processes. However, achieving this goal remains challenging due to optical aberrations and scattering from heterogeneous tissue structures, compounded by motion artifacts from awake animals. In this study, we developed a rapid and accurate adaptive optics system called multiplexing digital focus sensing and shaping (MD-FSS) for deep-tissue multiphoton microscopy. Under two-photon excitation, MD-FSS precisely measures the aberrated point spread function in approximately 0.1 s per measurement, effectively compensating for both aberrations and scattering to achieve subcellular resolution in deep tissue. Using MD-FSS integrated with two-photon microscopy, we achieved high-resolution brain imaging through thinned or optically cleared skull windows, two near noninvasive methods to access mouse brain, reaching depths up to 600 m below the pia in awake behaving mice. Our findings revealed significant differences in microglial functional states and microvascular circulation dynamics between awake and anesthetized conditions, highlighting the importance of studying brain function in awake mice through noninvasive methods. We captured functional imaging of fine neuronal structures at subcellular level in both somatosensory and visual cortices. Additionally, we demonstrated high-resolution imaging of microvascular structures and neurovascular coupling across multiple cortical regions and depths in the awake brain. Our work shows that MD-FSS robustly corrects tissue-induced aberrations and scattering through rapid PSF measurements, enabling near-noninvasive, high-resolution imaging in awake, behaving mice.

bioengineering↗

bioRxiv2023

Intravital microscopy of satellite cell dynamics and their interaction with myeloid cells during skeletal muscle regeneration

Skeletal muscle regeneration requires the highly coordinated cooperation of muscle satellite cells (MuSCs) with other cellular components. However, due to technical limitations, it remains unclear how MuSCs dynamically interact with non-myogenic cells, especially myeloid cells, in live animals. In this work, we developed a dual-laser multimodal nonlinear optical microscope platform to serve as an effective tool for studying the real-time interaction between MuSCs and non-myogenic cells during the early phase of muscle regeneration. Increased cell volume and mitochondrial mass, cell density, and myotube formation are indicative of MuSCs activation/growth, proliferation, and differentiation, respectively. Using 3D time-lapse imaging on live reporter mice containing both red fluorescence protein (RFP)-labeled macrophages and yellow fluorescence protein (YFP)-labeled MuSCs, and taking advantages of the autofluorescence of reduced nicotinamide adenine dinucleotide (NADH), we monitored the real-time spatiotemporal interaction between RFP+ macrophages/RFP- non-myogenic cells and YFP+ muscle stem/progenitor cells during the activation and the proliferation stages of regeneration. Our results indicated that their cell-cell contact was transient in nature. By inhibiting macrophage infiltration, we further showed that direct cell-cell contact between macrophages and MuSCs was not required for early activation of MuSCs before the proliferation stage. However, decreased macrophage infiltration impeded the proliferation and differentiation of MuSCs and also led to intramuscular fibrosis. Besides, neutrophil depletion in the CCR2 deficient mice did not delay the initial growth of MuSCs. These findings provide a new perspective on myeloid cells role during muscle regeneration.

cell biology↗

bioRxiv2018

The Association between Cigarette Affordability and Consumption

ObjectivesTo calculate cigarette affordability for 78 countries worldwide from 2001 to 2014 using the Relative Income Price (RIP) ratio defined as the percentage of per capita GDP required to purchase 100 packs of cigarettes using the lowest price from Economist Intelligence Unit (EIU) database, examine the association between cigarette affordability and cigarette consumption, and calculate the affordability elasticity of demand.\n\nDesign and MethodsRIP (2001-2014) was calculated for 16 low-income economies, 19 lower middle-income economies, 13 upper middle-income economies, and 30 high-income economies. Ordinary least square regressions were used to analyze the association between cigarette affordability and consumption.\n\nResults and ConclusionsPer capita consumption continued to rise in low-income countries and decreased slightly in lower middle-income countries as the RIP of cigarette consistently declined in low- and lower middle-income economies from 2001 to 2014. The real cigarette prices continued to decline in low- and lower middle-income countries and continued to rise in upper middle- and high-income countries. Though cigarettes were more expensive in HICs than were in LMICs, cigarettes were more affordable in HICs than were in LMICs. The regression results show a 10% increase in the RIP of cigarettes led to a 2% decrease in per capita consumption. The affordability elasticity of demand differed significantly between HICs and LMICs. However, the effect of cigarette affordability on consumption has not changed over time. To control the smoking epidemic, low- and lower middle-income countries should further increase cigarette prices. The rate of price increase should exceed the rate of economic growth and outpace the inflation rate to make cigarettes less affordable and thereby reducing tobacco use.

epidemiology↗