Biology subjects

Zhong, P.

Publications and source records attributed to Zhong, P..

11 recordsLinked to original sources

bioRxiv2026

Constrained Laser-Induced Cavitation for Miniaturized Treatment of Deep Vein Thrombosis

Chronic, mechanically resilient thrombi remain difficult to remove rapidly and safely using existing therapies, which are limited by slow treatment speeds, reduced efficacy against aged clots and risks associated with embolic debris. Here we introduce Constrained Laser-Induced Cavitation (CLIC), a novel approach that confines laser-induced cavitation bubble generation and collapse within a miniaturized waveguide to enhance thrombolysis. Optimized CLIC removed retracted clots at a mass-loss rate of 393.5 mg/min, [~]40-fold higher than reported state-of-the-art sonothrombolysis under similar conditions. Systematic variation of channel length and laser parameters showed that CLIC efficacy depends strongly on treatment geometry and cavitation dynamics. Post-treatment analysis revealed cylindrical channels consistent with clot removal dominated by fluid jetting and suction-driven evacuation, with cavitation shockwaves likely contributing a secondary role. Debris fragment measurements remained predominantly below a 1 mm embolic-risk threshold, consistent with a promising embolic safety profile. These findings establish CLIC as a viable strategy for rapid thrombolysis of chronic, mechanically resistant thrombi.

bioengineering↗

bioRxiv2026

Mating imperatives drive plasticity of the daily temporal niche via dopamine signaling.

Animals confine their daily activity to distinct diurnal, crepuscular, or nocturnal windows. It remains unclear how hundreds of sympatric species sharing the same temporal niche manage to coexist. To address this, we monitored the daily activity of the twilight-active, species-rich Drosophila genus under naturalistic conditions. Here, we show that intense sociosexual interactions rapidly drive a species-specific reformatting of their canonical crepuscular niche. The dominant sensory modality used for sexual communication predicts niche shift direction: reliance on chemosensation for courtship redirects behavioral activity into the night, while visual reliance shifts it into the day. This temporal plasticity bypasses the circadian clock, instead operating via a conserved dopaminergic pathway that simultaneously inhibits sleep and sustains sexual motivation. Our results reveal how mating imperatives enable conditional colonization of otherwise restricted temporal windows. Ultimately, by driving the divergence of previously overlapping niches, sociosexually induced temporal plasticity provides a powerful mechanism for sympatric coexistence in crowded environments.

neuroscience↗

bioRxiv2026

3D Passive Cavitation Mapping (3D-PCM) with a Large-aperture Planar Array

Urinary stone disease is a common urological condition with increasing incidence, particularly in developed countries. Laser lithotripsy (LL) has become a preferred minimally invasive treatment due to its high precision and low tissue damage. Recent studies suggest that cavitation plays a critical role in stone damage during LL, and three-dimensional passive cavitation mapping (3D-PCM) has emerged as a promising tool for detecting these events. However, clinical translation of 3D-PCM remains challenging due to limitations in imaging depth, field of view (FOV), and procedural compatibility. Here, we present a large-FOV dual-modality imaging system (3D-PCM and B-mode ultrasound) based on a large-aperture planar ultrasound array. Through array optimization and model-based reconstruction, our system achieves an expanded FOV of [~]40 x 40 mm2 at a clinically relevant imaging depth of [~]110 mm, while maintaining high spatial resolution of [~]0.6 mm laterally and [~]0.4 mm axially. In vivo experiments in a porcine model demonstrate that the reconstructed cavitation distribution correlates well with stone damage. Our technology has the potential to provide real-time treatment feedback during LL without disrupting the standard workflow.

bioengineering↗

bioRxiv2026

Hypothalamic MCH neurons links tau pathology to sleep disruption

Sleep disruption is an early and pervasive feature of Alzheimers disease (AD), yet the circuit mechanisms linking tau pathology to sleep-wake dysfunction remain unresolved. Here, we identify melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) as a critical node disrupted in tauopathy. Longitudinal EEG/EMG recordings in PS19 mice reveal progressive impairments in sleep architecture and homeostasis. Histological analyses revealed significant degeneration of both MCH neurons and the neighboring hypocretin (Hcrt) neuronal population in the LH at late stages of tauopathy. In vivo fiber photometry recordings demonstrated a selective functional impairment of MCH neurons, characterized by reduced activity during REM sleep, whereas Hcrt neuronal activity remained largely preserved. In addition, cell-autonomous expression of mutant tau in MCH neurons recapitulates sleep disruption, establishing a causal role. Despite tauopathy-induced neuronal loss and reduced endogenous activity, optogenetic and chemogenetic activation show that MCH neurons retain functional capacity, and their activation restores sleep in aged PS19 mice. Together, these findings define a circuit mechanism linking tau pathology to sleep and identify MCH neurons as a tractable therapeutic target.

neuroscience↗

bioRxiv2026

Visibly Transparent, Near-Infrared Absorbing Nanofluids Enable High-Efficiency and Safe Laser Lithotripsy

Laser lithotripsy (LL) is the gold standard for urinary stone management yet maximizing ablation efficiency while maintaining procedural safety remains clinically challenging. Here, we present a visibly transparent, near-infrared (NIR)-absorbing ITO@SiO2 nanofluid irrigation strategy that significantly enhances LL efficiency without compromising endoscopic visibility. By spectrally matching the absorption profile of ITO@SiO2 with the clinical Holmium:YAG laser wavelength, ablation efficiency improved by >200% in the bench-top spot treatments and >100% in the hydrogel kidney model. Mechanistic investigations revealed that the enhanced optical absorption of the nanofluid modifies bubble dynamics and synergistically amplifies photothermal/microexplosion effects and cavitation damage. Importantly, both in-vitro hydrogel and in-vivo porcine kidney models demonstrated a substantial thermal safety margin (maximum temperatures <35 {degrees}C) and excellent acute biocompatibility, with no evidence of thermal tissue injury. Integrating seamlessly into established clinical workflows without requiring stone pretreatment, this strategy offers a highly translatable, safe, and efficient platform for next-generation endoscopic lithotripsy.

bioengineering↗

bioRxiv2025

Intra-Crater Bubble Expansion Drives the Fracture of Impacted Ureteral Stones in Laser Lithotripsy

ObjectivesTo investigate the fracture mechanism of impacted ureteral stones during laser lithotripsy (LL). Materials and MethodsImpacted 6 x 6 mm cylindrical BegoStone samples embedded in a hydrogel ureter model were treated using either Holmium:YAG (Ho:YAG) laser or Thulium Fiber Laser (TFL) via three clinical strategies: "drill and core", contact, and non-contact modes. Laser pulses were delivered using three pulse energy/frequency settings: 0.8 J/12 Hz, 1.0 J/10 Hz, and 1.2 J/8 Hz with a 3 s on/3 s off protocol, under continuous irrigation at 40 mL/min. Crater formation, surface crack development, and bubble dynamics were assessed via optical coherence tomography, video, and high-speed photography. To delineate the contributions of different plausible damage mechanisms, bubble collapse was suppressed by leveraging the ureteroscopes proximity effect, and thermal ablation was minimized by treating donut-shaped stones with a central tunnel. The role of bubble expansion in stone fracture was further evaluated by systematically varying tunnel size or pulse energy. ResultsSurface cracks and stone fracture were observed exclusively in Ho:YAG laser-treated stones using the "drill and core", but not the other two strategies. TFL produced deeper craters yet failed to induce any significant crack formation or propagation under all conditions. Suppression of bubble collapse or thermal ablation had minimal effect on surface crack formation and growth. In contrast, the extent and number of surface cracks correlated strongly with the maximum lateral diameter and expansion rate of the vapor bubbles - two parameters that were significantly greater for Ho:YAG laser than TFL. Importantly, the crack formation also showed an inverse correlation with the size of the initial crater or tunnel in the stone. ConclusionIntra-crater bubble expansion, rather than thermal ablation or bubble collapse, is the primary mechanism driving the fracture of impacted ureteral stone in LL.

bioengineering↗

bioRxiv2025

Cognitive and Synaptic Impairment Induced by Deficiency of Autism Risk Gene Smarcc2 and its Rescue by Histone Deacetylase Inhibition

SMARCC2, which encodes BAF170, a core subunit of chromatin remodeling BAF complex, is one of the top-ranking risk genes for autism spectrum disorder (ASD). However, the mechanisms linking SMARCC2 haploinsufficiency to ASD remain poorly understood. Genome-wide RNA-seq analysis revealed that SMARCC2 was significantly diminished in iPSC-derived neurons from idiopathic ASD patients. ChIP-seq of SMARCC2 demonstrated its binding to many other ASD risk genes involved in transcriptional regulation. Smarcc2 deficiency in prefrontal cortex (PFC) of adolescent mice led to impaired working memory, with largely intact social and anxiety-like behaviors. Significant downregulation of genes enriched in synaptic transmission were found in PFC of Smarcc2-deficient mice by RNA-seq and qPCR profiling. In parallel, electrophysiological recordings uncovered the significant impairment of GABAergic and glutamatergic synaptic currents in Smarcc2-deficient PFC pyramidal neurons. Smarcc2 bound to HDAC2, and Smarcc2 deficiency led to the reduced global histone acetylation and H3K9ac enrichment at synaptic gene Slc1a3 (EAAT1), Slc6a1 (GAT1), and Slc32a1 (VGAT) promoters. Treatment of Smarcc2-deficient mice with romidepsin, a class I HDAC inhibitor, restored histone acetylation, working memory and some synaptic gene expression. These findings highlight the critical role of Smarcc2 in regulating cognitive and synaptic function, suggesting that targeting HDAC could alleviate deficits in Smarcc2-associated neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

Enhanced Treatment Efficiency of Holmium:YAG Laser Lithotripsy by Using PEDOT:PSS Nanofluid

Urinary stone disease, characterized by the formation of hard mineral deposits in the urinary tract, has seen a rising prevalence in the U.S. in recent years. This condition often leads to severe pain and typically requires medical intervention. Laser lithotripsy, a minimally invasive treatment, uses laser energy to fragment urinary stones into smaller pieces, facilitating easier removal or natural passage. Among available laser technologies, the holmium:yttrium-aluminum-garnet (Ho:YAG) laser has established itself as the gold standard over the past three decades. Efforts to improve Ho:YAG laser ablation efficiency have largely focused on adjusting laser parameters such as pulse energy and frequency. In this study, we proposed a nanoplasmonic engineering strategy by incorporating nanoparticles (NPs) with strong near-infrared (NIR) absorption into the fluid surrounding the stone, enhancing the light-matter interaction. Using a 0.03 wt.% PEDOT:PSS nanofluid, stone ablation efficiency improved by 38-727% in spot treatment and 26-75% in scanning treatment with a clinical laser lithotripter. The highly absorbing nanofluid accelerates vapor tunnel formation, boosts laser energy transmission to the stone, and permeates stone pores to enhance damage, without increasing thermal tissue injury risk. Cytotoxicity tests also confirmed minimal toxicity at appropriate concentrations. This nanofluid-based approach offers a promising advancement for more efficient and safer laser lithotripsy.

bioengineering↗

bioRxiv2022

The Optimal Combination of Scanning Speed and Fiber-to-Stone Distance for Effective and Efficient Dusting during Holmium: YAG Laser Lithotripsy

ObjectivesTo investigate mechanistically the effects of fiber scanning speed (vfiber) and fiber tip-to-stone standoff distance (SD) on dusting efficiency during Holmium (Ho): YAG laser lithotripsy (LL) Materials and MethodsPre-soaked BegoStone samples (23 x 23 x 4 mm, W x L x H) were treated in water using a clinical Ho:YAG laser in dusting mode (0.2 J pulse energy delivered at 20 Hz frequency) at three different SDs (0.10, 0.25 and 0.50 mm) with vfiber in the range of 0 to 10 mm/s. Stone damage was quantified by optical coherence tomography, bubble dynamics were captured by high-speed imaging, and associated pressure transients were measured using a needle hydrophone. To compare photothermal ablation vs. cavitation in stone dusting, the experiments were further repeated in air (photothermal ablation only), and in water with the fiber tip advanced at a short (0.25 mm) offset distance (OSD) from a ureteroscope to mitigate the bubble collapse toward the stone surface, thus eliminating cavitation-induced damage. ResultsCompared to the craters produced by a stationary fiber, the damage troughs produced by a scanning fiber after 100 pulses were significantly larger in volume. The optimal vfiber for maximum dusting efficiency was found to be 3.5 mm/s for SD = 0.10 [~] 0.25 mm, resulting in long (17.5 mm), shallow (0.14 - 0.15 mm) and narrow (0.3 - 0.4 mm) troughs. In contrast, the maximum stone damage was produced at an optimal vfiber of 0.5 mm/s for SD = 0.50 mm, which generates much shorter (2.5 mm), yet deeper (0.35 mm) and wider (1.4 mm) troughs. Greater stone damage was produced in water than in air, especially at vfiber = 0 - 3.5 mm/s. With the scope end placed near the fiber tip, stone damage could be significantly reduced in water by 29% - 58% for SD = 0.10 mm, by 51% - 82% for SD = 0.25 mm, and by 66% - 100 % for SD = 0.50 mm, compared to those produced without the scope. Together, these findings suggest that cavitation plays an indispensable role in stone dusting by scanning treatment. Moreover, under clinically relevant vfiber (1 [~] 3 mm/s), dusting at SD = 0.5 mm (i.e., non-contact mode) may leverage higher frequency of the laser (e.g., 40 to 120 Hz) to harvest the full potential of cavitation damage while significantly reducing the procedure time, compared to its counterpart at SD = 0.1 mm (i.e., contact mode) that promotes photothermal ablation. ConclusionDusting efficiency during Ho:YAG LL may be substantially improved by utilizing the optimal combination of vfiber and SD for a given frequency.

bioengineering↗

bioRxiv2020

Mechanically Induced Integrin Ligation Mediates Intracellular Calcium Signaling with Single Pulsating Cavitation Bubbles

Ultrasound or shockwave-induced cavitation is used therapeutically to stimulate neural and muscle tissue, but the mechanisms underlying this mechanotransduction are unclear. Intracellular Ca2+ signaling is one of the earliest events in mechanotransduction. In this study, we investigate the mechanism of Ca2+ signaling in individual HEK293T cells stimulated by single cavitation bubbles. Ca2+ responses are rare at cell-bubble distance that avoids membrane poration, even with overexpression of the mechanosensitive ion channel Piezo1, but could be increased in frequency to 42% of cells by attaching RGD beads to the apical surface of the cells. By using Piezo1 knockout and Piezo1-expressing cells, integrin-blocking antibodies, and inhibitors of P2X ion channels, key molecular players are identified in the RGD bead-enhanced Ca2+ response: increased integrin ligation by substrate ECM triggers ATP release and activation of P2X--but not Piezo1--ion channels. These molecular players have not been examined previously in cavitation-induced Ca2+ signaling. The resultant Ca2+ influx causes dynamic changes in cell spread area. This approach to eliciting a Ca2+ response with cavitation microbubbles without cell injury, and the uncovered mechanotransduction mechanism by which increased integrin-ligation mediates ATP release and Ca2+ signaling will inform new strategies to stimulate tissues with ultrasound and shockwaves.

biophysics↗

bioRxiv2020

Cortical microinfarcts potentiate recurrent ischemic injury through NLRP3-dependent trained immunity

Microinfarcts are common among the elderly, and patients with microinfarcts are more vulnerable to another stroke. However, the potential effect of microinfarct on recurrent stroke remains elusive. In this study, we investigated the detrimental effect of microinfarct on recurrent stroke in mice. Microinfarct was induced using two-photon laser and photothrombotic stroke was induced in the cortex contralateral to microinfarct four weeks later. We found that CMI could trigger the formation of innate immune memory, which exacerbated the pro-inflammatory response and ischemic injury in second photothrombotic stroke. Furthermore, we clarified the role of NLRP3 inflammasome in the nuclei of microglia, which interacts with the MLL1 complex and thereby increases H3K4 methylation, suggesting that NLRP3 is critical in microinfarct-induced innate immune memory. Additionally, NLRP3 knockout in microglia attenuated microinfarct-induced detrimental effects on recurrent stroke. Our study highlights the detrimental effect of trained immunity on the recurrent stroke and reveals the important role of NLRP3 in mediating the formation of this memory, which may be a therapeutic target to mitigate recurrent strokes.

immunology↗