Biology subjects

Kang, P.

Publications and source records attributed to Kang, P..

At least 19 recordsLinked to original sources

bioRxiv2025

Modulating inter-mitochondrial contacts to increase membrane potential for mitigating blue light damage

Mitochondrial membrane potential (MMP) is essential for mitochondrial functions, yet current methods for modulating MMP lack precise spatial and temporal control. Here, we present an optogenetic system that enables reversible formation of inter-mitochondrial contacts (mito-contacts) with high spatiotemporal precision. Blue light stimulation induces rapid formation of mito-contacts, which fully dissipate upon cessation of illumination. These light-induced mito-contacts can enhance MMP, leading to increased ATP production under stress conditions. Moreover, in human retinal cells and C. elegans, high MMP induced by mito-contacts alleviates the deleterious effects of prolonged blue light exposure, restoring energy metabolism and extending organismal lifespan. This optogenetic approach provides a powerful tool for modulating MMP and offers potential therapeutic applications for diseases linked to mitochondrial dysfunction.

biophysics↗

bioRxiv2023

Ptth regulates lifespan through innate immunity pathway in Drosophila

The prothoracicotropic hormone (PTTH) is a well-known neuropeptide that regulates insect metamorphosis (the juvenile-to-adult transition) by inducing the biosynthesis of steroid hormones. However, the role of PTTH in adult physiology and longevity is largely unexplored. Here, we show that Ptth loss-of-function mutants are long-lived and exhibit increased resistance to oxidative stress in Drosophila. Intriguingly, we find that loss of Ptth blunt age-dependent upregulation of NF-{kappa}B signaling specifically in fly hepatocytes (oenocytes). We further show that oenocyte-specific overexpression of Relish/NF-{kappa}B blocks the lifespan extension of Ptth mutants, suggesting that PTTH regulates lifespan through oenocyte-specific NF-{kappa}B signaling. Surprisingly, adult-specific knockdown of Ptth did not prolong lifespan, indicating that PTTH controls longevity through developmental programs. Indeed, knockdown of PTTH receptor Torso in prothoracic gland (PG) during fly development prolongs lifespan. To uncover the developmental processes underlying PTTH-regulated lifespan, we perform a developmental transcriptomic analysis and identify an unexpected activation of NF-{kappa}B signaling in developing oenocytes during fly metamorphosis, which is blocked in Ptth mutants. Importantly, knockdown of Relish/NF-{kappa}B specifically in oenocytes during early pupal stages significantly prolongs the lifespan of adult flies. Thus, our findings uncover an unexpected role of PTTH in controlling adult lifespan through temporal and spatial activation of NF-{kappa}B signaling in developing hepatocytes and highlight the vital role of developmental NF-{kappa}B signaling in shaping adult physiology. Significance StatementDespite the strong link between animal development and adult lifespan, we know little about how developmental programs impact adult longevity, and when and where such programs are activated during development. Here, we demonstrate that loss of insect hormone PTTH prolongs lifespan and healthspan by repressing chronic inflammation in Drosophila. Intriguingly, we demonstrate that PTTH regulates adult lifespan through temporal and spatial activation of NF-{kappa}B signaling in developing hepatocytes during insect metamorphosis. These findings provide novel insights into the developmental programs that impact adult longevity.

physiology↗

bioRxiv2022

Soft and stretchable organic bioelectronics for continuous intra-operative neurophysiological monitoring during microsurgery

Continuous intra-operative neurophysiological monitoring (CINM) that provides precise mapping of neural anatomy through the entire microsurgery process is essential to preserve the structural and functional integrity of the nerve. However, bulky and rigid electrodes used currently in clinics are usually unable to reliably maintain continuous and stable contacts with the vulnerable and complex nerve networks, thus often resulting in detrimental post-operative complications, such as hemiplegia and sensory disturbances. Here, we describe a biomechanically compatible, suture-free, and individually reconfigurable CINM based on soft and stretchable organic electronic materials. Due to both low impedance and modulus of our conducting polymer electrodes, we achieved for the first time continuous recording of near-field action potential with high signal-to-noise ratio and minimal invasiveness during microsurgeries. Utilizing this unprecedented CINM modality, in conjunction with localized neurostimulation, we further demonstrated our approach in enabling optimal post-operative prognosis in preclinical animal models by preserving normal neural functions after a variety of tumor resection surgeries.

bioengineering↗

bioRxiv2022

Synthetic EMG Based on Adversarial Style Transfer can Effectively Attack Biometric-based Personal Identification Models

Biometric-based personal identification models are generally considered to be accurate and secure because biological signals are too complex and person-specific to be fabricated, and EMG signals, in particular, have been used as biological identification tokens due to their high dimension and non-linearity. We investigate the possibility of effectively attacking EMG-based identification models with biological adversarial input via a novel EMG signal individual style transformer based on a generative adversarial network. EMG hand gesture data from eighteen subjects and three well-recognized deep EMG classifiers were used to demonstrate the effectiveness of the proposed attack methods. The proposed methods achieved an average of 99.41% success rate on confusing identification models and an average of 91.51% success rate on manipulating identification models. These results demonstrate that EMG classifiers based on deep neural networks can be vulnerable to synthetic data attacks. The proof-of-concept results reveal that synthetic EMG biological signals must be considered in biological identification system design across a vast array of relevant biometric systems to ensure personal identification security for individuals and institutions.

neuroscience↗

bioRxiv2022

Significantly amplified photoacoustic effect for silica-coated gold nanoparticles by interface heat transfer mechanisms

Plasmonic gold nanoparticles (AuNPs) are effective photoacoustic (PA) signal agents and have found important biomedical applications. The silica coating on the surface of AuNPs showed enhanced PA efficiency, however, the PA amplification mechanism remains unclear. Here, we systematically studied the silica coating effect on PA generation of AuNPs under different laser pulse durations. We experimentally demonstrated up to 4-fold PA amplification under thin silica coating (<5 nm) and a picosecond laser excitation. The theoretical model further suggests that the PA amplification originates from two interface heat transfer mechanisms including 1) the enhanced interface thermal conductance on the silica-water interface and 2) the electron-phonon energy transfer channel on the gold/silica interface. This study discovers a regime of large PA amplification and provides a new rationale for plasmonic nanoparticle design to achieve better PA efficiency.

bioengineering↗

bioRxiv2022

Connexin43 Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Rat Glucocorticoid-Induced Osteonecrosis of the Femoral Head

Glucocorticoids induced osteonecrosis of the femoral head (GIONFH) is a devastating orthopedic disease. Previous studies suggested that connexin43 (Cx43) is involved in the process of osteogenesis and angiogenesis. However, the role of Cx43 potentiates in the osteogenesis and angiogenesis of bone marrow-derived stromal stem cells (BMSCs) in GIONFH is still not investigated. In this study, BMSCs were isolated and transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and Cx43. The osteogenic differentiation of BMSCs were detected after transfected with Cx43. In addition, the migration abilities and angiogenesis of human umbilical vein endothelial cells (HUVECs) were been detected after induced by transfected BMSCs supernatants in vitro. Our results showed that Cx43 overexpression in BMSCs promoted osteogenic differentiation and angiogenesis in vitro. Finally, we established GC-ONFH rat model, then, a certain amount of transfected or controlled BMSCs were injected into the tibia of the rats. Immunohistological staining and micro-CT scanning results showed that the transplanted experiment group had significantly promoted more bone regeneration, vessel volume and the expressions of Runx2, ALP, COL I, VEGF and CD31 when compared with the effects of the negative or control groups. This study demonstrated for the first time that the Cx43 overexpression in BMSCs could promote bone regeneration as seen in the osteogenesis and angiogenesis process, suggesting that Cx43 may serve as a therapeutic gene target for GIONFH treatment.

cell biology↗

bioRxiv2022

Acetyl-CoA mediated autoacetylation of fatty acid synthase in de novo lipogenesis

De novo lipogenesis (DNL) is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged during Drosophila larval development when lipogenesis is hyperactive. Instead, acetylation modification of FASN is highly upregulated in fast-growing larvae. We further show that lysine K813 is highly acetylated in developing larvae, and its acetylation is required for upregulated FASN activity, body fat accumulation, and normal development. Intriguingly, K813 is rapidly autoacetylated by acetyl-CoA in a dosage-dependent manner, independent of known acetyltransferases. Furthermore, the autoacetylation of K813 is mediated by a conserved P-loop-like motif (N-xx-G-x-A). In summary, this work uncovers a novel role of acetyl-CoA-mediated autoacetylation of FASN in developmental lipogenesis and reveals a self-regulatory system that controls metabolic homeostasis by linking acetyl-CoA, lysine acetylation, and DNL. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/475252v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@db2042org.highwire.dtl.DTLVardef@22dde8org.highwire.dtl.DTLVardef@116b3a5org.highwire.dtl.DTLVardef@16c2dc9_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIAcetylation modification of FASN, but not protein expression, positively correlates with de novo lipogenesis during Drosophila larval development C_LIO_LISite-specific acetylation at K813 residue enhances FASN enzymatic activity C_LIO_LIK813 residue is autoacetylated by acetyl-CoA, independent of KATs C_LIO_LIA novel N-xx-G-x-A motif is required for autoacetylation of K813 C_LI

developmental biology↗

bioRxiv2021

Learning from ingroup experiences changes intergroup impressions

Living in multicultural societies, humans form impressions towards individuals of their own social groups (ingroup members) and of different social groups (outgroup members). Some psychological theories predict that intergroup impressions are mainly shaped by experiences with outgroup individuals ("outgroup focused theories"), while other theories predict that ingroup experiences play a dominant role ("ingroup focused theories"). Here we test predictions from these two psychological theories by estimating how intergroup impressions are dynamically shaped when people learn from both ingroup and outgroup experiences. Participants expected to receive painful shocks but were saved from pain by different ingroup or outgroup members in 75% of all trials. We measured neural responses using functional magnetic resonance imaging (fMRI), and participants rated their social closeness as well as impressions towards the ingroup and the outgroup. Behavioral results showed an initial ingroup bias in impression ratings which was significantly reduced over the course of learning. Computational learning models revealed that these changes in intergroup impressions were predicted by the weight given to ingroup prediction errors. The weight of the ingroup prediction error and its effect on intergroup impression change was stronger the more individuals identified with their ingroup. On the neural level, the left inferior parietal lobule (IPL) encoded more negative prediction errors for the ingroup compared to the outgroup. Moreover, stronger weight for ingroup prediction errors was related to increased neural coupling between the left IPL and the anterior insula (AI). This coupling further predicted learning-related changes in intergroup impressions. Together, our work provides computational and neural evidence for "ingroup focused theories", highlighting the importance of ingroup experiences in shaping social impressions in intergroup settings.

neuroscience↗

bioRxiv2021

Single Pulse Heating of Nanoparticle Array for Biological Applications

With the ability to convert external excitation into heat, nanomaterials play an essential role in many biomedical applications. Two modes of nanoparticle (NP) array heating, nanoscale-confined heating (NCH) and macroscale-collective heating (MCH), have been found and extensively studied. Despite this, the resulting biological response at protein level remains elusive. In this study, we developed a computational model to systematically investigate the single-pulsed heating of NP array and corresponding protein denaturation/activation. We found that NCH may lead to targeted protein denaturation, however, nanoparticle heating does not lead to nanoscale selective TRPV1 channel activation. The excitation duration and NP concentration are primary factors that determine a window for targeted protein denaturation, and together with heating power, we defined quantified boundaries for targeted protein denaturation. Our results boost our understandings in the NCH and MCH under realistic physical constraints and provide a robust guidance to customize biomedical platforms with desired NP heating.

bioengineering↗

bioRxiv2021

Nanoparticle fragmentation at solid state under single picosecond laser pulse stimulation

Understanding the laser-nanomaterials interaction including nanomaterial fragmentation has important implications in nanoparticle manufacturing, energy, and biomedical sciences. So far, three mechanisms of laser-induced fragmentation have been recognized including non-thermal processes and thermomechanical force under femtosecond pulses, and the phase transitions under nanosecond pulses. Here we show that single picosecond (ps) laser pulse stimulation leads to anomalous fragmentation of gold nanoparticles that deviates from these three mechanisms. The ps laser fragmentation was weakly dependent on particle size, and it resulted in a bimodal size distribution. Importantly, ps laser stimulation fragmented particles below the melting point and below the threshold for non-thermal mechanism. This study reveals a previously unknown regime of nanoparticle fragmentation.

biochemistry↗

bioRxiv2021

Physachenolide C induces complete regression of established murine melanoma tumors via apoptosis and cell cycle arrest

Melanoma is an aggressive skin cancer that metastasizes to other organs. While immune checkpoint blockade with anti-PD-1 has transformed the treatment of advanced melanoma, many melanoma patients fail to respond to anti-PD-1 therapy or develop acquired resistance. Thus, effective treatment of melanoma still represents an unmet clinical need. Our prior studies support the anti-cancer activity of the 17{beta}-hydroxywithanolide class of natural products, including physachenolide C (PCC). As single agents, PCC and its semi-synthetic analog demonstrated direct cytotoxicity in a panel of murine melanoma cell lines, which share common driver mutations with human melanoma; the IC50 values ranged from 0.18 - 1.7 {micro}M. PCC treatment induced apoptosis of tumor cells both in vitro and in vivo. In vivo treatment with PCC alone caused the complete regression of established melanoma tumors in all mice, with a durable response in 33% of mice after discontinuation of treatment. T cell-mediated immunity did not contribute to the therapeutic efficacy of PCC or prevent tumor recurrence in YUMM2.1 melanoma model. In addition to apoptosis, PCC treatment induced G0-G1 cell cycle arrest of melanoma cells, which upon removal of PCC, re-entered the cell cycle. PCC-induced cycle cell arrest likely contributed to the in vivo tumor recurrence in a portion of mice after discontinuation of treatment. Thus, 17{beta}-hydroxywithanolides have the potential to improve the therapeutic outcome for patients with advanced melanoma.

cancer biology↗

bioRxiv2020

Modulating the Blood-Brain Barrier by Light Stimulation of Molecular-Targeted Nanoparticles

The blood-brain barrier (BBB) tightly regulates the entry of molecules into the brain by tight junctions that seals the paracellular space and receptor-mediated transcytosis. It remains elusive to selectively modulate these mechanisms and to overcome BBB without significant neurotoxicity. Here we report that light stimulation of tight junction-targeted plasmonic nanoparticles selectively opens up the paracellular route to allow diffusion through the compromised tight junction and into the brain parenchyma. The BBB modulation does not impair vascular dynamics and associated neurovascular coupling, or cause significant neural injury. It further allows antibody and adeno-associated virus delivery into local brain regions. This novel method offers the first evidence of selectively modulating BBB tight junctions and opens new avenues for therapeutic interventions in the central nervous system. One Sentence SummaryGentle stimulation of molecular-targeted nanoparticles selectively opens up the paracellular pathway and allows macromolecules and gene therapy vectors into the brain.

neuroscience↗

bioRxiv2020

Computational investigation of protein photoinactivation by molecular hyperthermia

To precisely control protein activity in a living system is a challenging yet long-pursued objective in biomedical sciences. Recently we have developed a new approach named molecular hyperthermia (MH) to photoinactivate protein activity of interest without genetic modification. MH utilizes nanosecond laser pulse to create nanoscale heating around plasmonic nanoparticles to inactivate adjacent protein in live cells. Here we use a numerical model to study important parameters and conditions for MH to efficiently inactivate proteins in nanoscale. To quantify the protein inactivation process, the impact zone is defined as the range where proteins will be inactivated by nanoparticle localized heating. Factors that reduce the MH impact zone include stretching the laser pulse duration, temperature-dependent thermal conductivity (versus constant properties), and non-spherical nanoparticle geometry. In contrast, the impact zone is insensitive to temperature-dependent material density and specific heat, as well as thermal interface resistance based on reported data. The low thermal conductivity of cytoplasm increases the impact zone. Different proteins with various Arrhenius kinetic parameters have significantly different impact zones. This study provides guidelines to design the protein inactivation process in MH.

bioengineering↗

bioRxiv2020

Impaired hand dexterity function in a non-human primate model with chronic Parkinson's disease

Symptoms of Parkinsons disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed an alteration in Parkinsonian tremor symptoms, loss of dopaminergic neuron, and positron emission tomography (PET) imaging of dopamine transporters (DAT) in these models. HDT latency significantly increased in NHP-PD models. In addition, a significant inverse correlation between HDT and DAT was identified, but no local bias was found. The correlation with intention tremor symptoms was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

neuroscience↗

bioRxiv2020

Embedded Enzyme Nanoclusters Depolymerize Polyesters via Chain-End Mediated Processive Degradation

Many bioactive elements, long perceived as non-viable for material development, are now emerging as viable building blocks to encode material lifecycle and to ensure our harmonious existence with nature. Yet, there is a significant knowledge gap on how bio-elements interface with synthetic counterparts and function outside of their native environments. Here, we show that when enzymes are dispersed as nanoclusters confined within macromolecular matrices, their reaction kinetics, pathway, and substrate selectivity can be modulated to achieve programmable polymer degradation down to repolymerizable small molecules. Specifically, when enzyme nanoclusters are dispersed in trace amount (~0.02 wt%) in polyesters, i.e. poly(caprolactone) (PCL) and poly(lactic acid) (PLA), chain-end mediated processive depolymerization can be realized, leading to scalable bioactive plastics for efficient sorting, such as recovery of precious metal filler from flexible electronics. Present studies demonstrate that when the enzyme is confined at dimensions similar to that of polymer chains, their behaviors are governed by the polymer conformation, segmental dynamic and thermal history, highlighting the importance to consider bioactive plastics differently from solution enzymology.

bioengineering↗

bioRxiv2020

Inhibitory effect of the TSG-6 on the BMP-4/Smad signaling pathway and odonto/osteogenic differentiation of dental pulp stem cells

This study aimed to observe the molecular mechanism underlying the effect of tumor necrosis factor-inducible protein 6 (TSG-6) on the bone morphogenetic protein-4 (BMP-4)/drosophila mothers against decapentaplegic protein(Smad) signaling pathway and mineralization of dental pulp stem cells (DPSCs) in inflammatory environment. Normal and TSG-6 gene-modified DPSCs were cultured in a mineralization-inducing fluid containing 0 and 50 ng/mL TNF- separately. The real-time polymerase chain reaction was used to measure the expression of TSG-6 and odonto/osteogenic differentiation makers at the mRNA level. Western blot analysis and cellular immunofluorescence were used to observe the odonto/osteogenic differentiation of DPSCs and the variation of BMP-4/Smad signaling pathway at the protein level. Moreover, normal and modified DPSCs combined with hydrogel were used for subcutaneous implantation in nude mice. The expression of odonto/osteogenic markers and BMP-4/Smad-related proteins was lower in Ad-TSG-6 DPSCs than in normal DPSCs after mineralization induction, and was higher in TSG-6-RNAi DPSCs than in normal DPSCs after culturing with mineralization-inducing fluid containing 50 ng/mL TNF-. The subcutaneous transplantation of normal and modified DPSCs combined with hydrogel in nude mice demonstrated that normal DPSCs were formed in the tissue containing collagen. The tissue formed by Ad-TSG-6 DPSCs was highly variable, and the cells were very dense. The expression of odonto/osteogenic markers of Ad-TSG-6 DPSCs were lower in Ad-TSG-6 DPSCs than in normal DPSCs. We can know that TNF- regulates the expression of TSG-6, thereby inhibiting the BMP-4/Smad signaling pathway and the odonto/osteogenic differentiation ability of DPSCs.

cell biology↗

bioRxiv2019

Impaired peroxisomal import in Drosophila hepatocyte-like cells induces cardiac dysfunction through the pro-inflammatory cytokine Upd3

Age is a major risk factor for cardiovascular diseases. Currently, the non-autonomous regulation of age-related cardiac dysfunction is poorly understood. In the present study, we discover that age-dependent induction of cytokine unpaired 3 (Upd3) in Drosophila oenocytes (hepatocyte-like cells), due to a dampened peroxisomal import function, is the primary non-autonomous mechanism for elevated arrhythmicity in old hearts. We show that Upd3 is significantly up-regulated (52-fold) in aged oenocytes. Oenocyte-specific knockdown of Upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of Upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. Intriguingly, oenocyte-specific over-expression of Pex5, the key peroxisomal import receptor, restores peroxisomal import, blocks age-related Upd3 induction, and alleviates aging- and paraquat-induced cardiac arrhythmicity. Thus, our studies identify an important role of the evolutionarily conserved pro-inflammatory cytokine signaling and hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.

physiology↗

bioRxiv2019

Environment rapidly upregulates serotonin 2A receptor expression via the immediate early gene Egr3

Serotonin 2A receptors (5-HT2ARs) mediate the effects of hallucinogenic drugs and antipsychotic medications, and are reduced in schizophrenia patients brains. However, the mechanisms that regulate 5-HT2AR expression remain poorly understood. We show that an environmental stimulus, sleep deprivation, upregulates 5-HT2ARs in the mouse frontal cortex (FC) in just 6-8 hours. This induction requires the immediate early gene transcription factor early growth response 3 (Egr3). Further, EGR3 binds to the Htr2a promoter in the FC in vivo, and drives reporter construct expression in vitro via two Htr2a promoter binding sites. These findings suggest that EGR3 directly regulates FC Htr2a expression in response to physiologic stimuli, providing a mechanism by which environment rapidly alters levels of a brain receptor that mediates symptoms, and treatment, of mental illness. One Sentence SummaryJust 6-8 hours of sleep deprivation upregulates brain levels of the receptor that mediates the response to hallucinogens.

neuroscience↗