Chunyan Li

Shanghai Jiao Tong University

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Shankai Yin

Shanghai Sixth People's Hospital

Haibo Shi

Shanghai Jiao Tong University

Zhengnong Chen

Shanghai Sixth People's Hospital

Dongzhen Yu

Shanghai Sixth People's Hospital

Shankai Yin

Shanghai Jiao Tong University

Xin‐Lu Yin

Shanghai Sixth People's Hospital

Lu‐Yang Wang

University of Toronto

Quanjun Yang

Shanghai Jiao Tong University

Min Liang

Moderna Therapeutics (United States)

Yazhi Xing

Shanghai Sixth People's Hospital

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Shanghai Jiao Tong University

125

Shanghai Sixth People's Hospital

University of Toronto

Chinese Academy of Sciences

University of Calgary

Deleted Institution

Sun Yat-sen University

Fundação Oswaldo Cruz

Shanghai University of Traditional Chinese Medicine

Shanghai Mental Health Center

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Cytochrome P450 1A2 Is Incapable of Oxidizing Bilirubin Under Physiological Conditions

Frontiers in Pharmacology (2019)

Xinyi Li Dongzhen Yu Huiqun Jie Huiqun Zhou Haibo Ye

Background: Bilirubin (BR) is metabolized mainly by uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) through glucuronidation in the liver. Some studies have shown that several subtypes of cytochrome P450 (CYP) enzymes, including CYP1A2, are upregulated by inducers and proposed to be alternative BR degradation enzymes. However, no information is available on the BR degradation ability of CYP in normal rats without manipulation by CYP inducers. Methods: Quantitative real-time polymerase chain reaction (QRT-PCR), western blot, immunofluorescence, and confocal microscopy were used to find expression of CYP1A2 in the brain and the liver. BR metabolites in microsomal fractions during development were examined by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-MS/MS). Results: In the present study, we observed that CYP1A2 mRNA levels increased at postnatal days (P)14 and P30 with respect to the level at P7 both in liver and brain, this increment was especially pronounced in the brain at P14. The expression of CYP1A2 in the brainstem (BS) was higher than that in the cerebellum (CLL) and cortex (COR). Meanwhile, the CYP1A2 protein level was significantly higher in the COR than in the brainstem and CLL at P14. The levels of BR and its metabolites (m/z values 301, 315, 333 and biliverdin) were statistically unaltered by incubation with liver and brain microsomal fractions. Conclusion: Our results indicated that the region-specific expression of CYP1A2 increased during development, but CYP family enzymes were physiologically incapable of metabolizing BR. The ability of CYPs to oxidize BR may be triggered by CYP inducers.

Glucuronosyltransferase

10.3389/fphar.2019.01220

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Citations (3)

Accelerated Development of the First-Order Central Auditory Neurons With Spontaneous Activity

Frontiers in Molecular Neuroscience (2018)

Xin‐Lu Yin Huiqun Jie Min Liang Li-Na Gong Han‐Wei Liu

In developing sensory systems, elaborate morphological connectivity between peripheral cells and first-order central neurons emerges via genetic programming before the onset of sensory activities. However, how the first-order central neurons acquire the capacity to interface with peripheral cells remains elusive. By making patch-clamp recordings from mouse brainstem slices, we found that a subset of neurons in the cochlear nuclei, the first central station to receive peripheral acoustic impulses, exhibits spontaneous firings (SFs) as early as at birth, and the fraction of such neurons increases during the prehearing period. SFs are reduced but not eliminated by a cocktail of blockers for excitatory and inhibitory synaptic inputs, implicating the involvement of intrinsic pacemaker channels. Furthermore, we demonstrate that these intrinsic firings (IFs) are largely driven by hyperpolarization- and cyclic nucleotide-gated channel (HCN) mediated currents (Ih), as evidenced by their attenuation in the presence of HCN blockers or in neurons from HCN1 knockout mice. Interestingly, genetic deletion of HCN1 cannot be fully compensated by other pacemaker conductances and precludes age-dependent up regulation in the fraction of spontaneous active neurons and their firing rate. Surprisingly, neurons with SFs show accelerated development in excitability, spike waveform and firing pattern as well as synaptic pruning towards mature phenotypes compared to those without SFs. Our results imply that SFs of the first-order central neurons may reciprocally promote their wiring and firing with peripheral inputs, potentially enabling the correlated activity and crosstalk between the developing brain and external environment.

Stimulus (psychology)

Hyperpolarization

Bursting

10.3389/fnmol.2018.00183

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Efficient Inverted Perovskite Solar Cells with a Fill Factor Over 86% via Surface Modification of the Nickel Oxide Hole Contact

Advanced Functional Materials (2023)

Chunyan Li Yao Zhang Xiaojun Zhang Peng Zhang Xudong Yang

Abstract The poor interface quality between nickel oxide (NiO x ) and halide perovskites limits the performance and stability of NiO x ‐based perovskite solar cells (PSCs). Here a reactive surface modification approach based on the in situ decomposition of urea on the NiO x surface is reported. The pyrolysis of urea can reduce the high‐valence state of nickel and replace the adsorbed hydroxyl group with isocyanate. Combining theoretical and experimental analyses, the treated NiO x films present suppressed surface states and improved transport energy level alignment with the halide perovskite absorber. With this strategy, NiO x ‐based PSCs achieve a champion power conversion efficiency (PCE) of 23.61% and a fill factor of over 86%. The device's efficiency remains above 90% after 2000 h of thermal aging at 85 °C. Furthermore, perovskite solar modules achieve PCE values of 18.97% and 17.18% for areas of 16 and 196 cm 2 , respectively.

Non-blocking I/O

Nickel oxide

10.1002/adfm.202214774

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Comparison of healing of acute total tympanic membrane perforation between rats with and without excision of the mallear handle

Laryngoscope Investigative Otolaryngology (2023)

Zihan Lou Chunyan Li Dongzhen Yu Jingjing Wang Zhengnong Chen

Abstract Objective We compared the histological changes and hearing restoration during the healing of acute total tympanic membrane (TM) perforations between Sprague–Dawley (SD) rats with and without excision of the mallear handle. Materials and methods Bilateral, acute, and total TM perforations were created in 36 male SD rats. The mallear handle was preserved in the left ear (handle‐preserved ear [HPE]) and excised from the right ear (handle‐excised ear [HEE]). Endoscopical examination, auditory brainstem response (ABR) thresholds, histopathological, and scanning electron microscope (SEM) analysis were performed. Results Endoscopic photographs showed that all perforations in the 18 SD rats were closed. The mean closure times were 6.83 ± 0.85 and 8.50 ± 0.71 days in the HPE and HEE groups, respectively ( p < .001). SEM images showed radial arrangement of fiber bundles in a single direction in HPEs, although normal arrangement was not achieved. In contrast, HEEs showed disorganized arrangement. At 1 month after perforation closure, the ABR thresholds at high frequencies were significantly higher in the HEE group than in the HPE group ( p = .029 and p = .017 for 16 and 32 kHz, respectively). Additionally, the changes in ABR threshold were significantly different at high frequencies ( p = .011 and p = .017 for 16 and 32 kHz, respectively) before and 1 month after perforation closure between the HPE and HEE groups, although the differences were not statistically significant at the remaining frequencies. Conclusion Although the malleus handle may not affect the closure of total perforation in SD rats, it contributes to accelerate the perforation closure by possible guide the migration of proliferative epithelial cell on the upper halves of the annulus. Additionally, resection of the malleus handle impairs high frequency hearing recovery following spontaneous closure of the TM.

Perforation

Tympanic Membrane Perforation

Malleus

Closure (psychology)

10.1002/lio2.1175

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Evaluation of acoustic changes in and the healing outcomes of rat eardrums with pars tensa and pars flaccida perforations

Laryngoscope Investigative Otolaryngology (2022)

Yaoqian Liu Cuiping Wu Tingting Chen Qiyue Shen Yuanping Xiong

Abstract Objectives To systematically explore the differences in acoustic changes and healing outcomes of tympanic membranes (TMs) with pars flaccida perforation (PFP) and pars tensa perforation (PTP). Methods We created PFPs and PTPs of various sizes in Sprague–Dawley rats, and evaluated TM umbo velocity and hearing function using laser Doppler vibrometry and auditory brainstem response (ABR) measurement before and immediately after perforation. Two weeks later, hearing was reevaluated and TMs were investigated by immunohistochemical staining. Results Small PFPs and PTPs did not significantly affect umbo velocity and hearing function. Large PFPs increased umbo velocity loss at low frequency (1.5 kHz) and elevated ABR thresholds within 1–2 kHz. Large PTP caused significant velocity loss at low frequencies from 1.5 to 3.5 kHz and threshold elevations at full frequencies (1–2 kHz). Two weeks after the perforation, the hearing function of rats with healed PFPs recovered completely. However, high‐frequency hearing loss (16–32 kHz) persisted in rats with healed PTPs. Morphological staining revealed that no increase in the thickness and obvious increase in collagen I level of regenerated par flaccida; regenerated pars tensa exhibited obvious increase in thickness and increased collagen I, while the collagen II regeneration was limited with discontinuous and disordered structure in regenerated pars tensa. Conclusion The hearing loss caused by large PFP limits at low frequencies while large PTP can lead to hearing loss at wide range frequencies. PFP and PTP have different functional outcomes after spontaneous healing, which is determined by the discrepant structure reconstruction and collagen regeneration.

Perforation

10.1002/lio2.797

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Citations (2)

The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons

Toxicology Letters (2015)

Xin‐Lu Yin Min Liang Haibo Shi Lu‐Yang Wang Chunyan Li

Gamma-Aminobutyric Acid

10.1016/j.toxlet.2015.10.008

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Riluzole is a Promising Pharmacological Inhibitor of Bilirubin‐Induced Excitotoxicity in the Ventral Cochlear Nucleus

CNS Neuroscience & Therapeutics (2014)

Guo‐Ying Han Chunyan Li Haibo Shi Ji‐Ping Wang K. X. Su

Summary Background and purpose Bilirubin encephalopathy as a result of hyperbilirubinemia is a devastating neurological disorder that occurs mostly in the neonatal period. To date, no effective drug treatment is available. Glutamate‐mediated excitotoxicity is likely an important factor causing bilirubin encephalopathy. Thus, drugs suppressing the overrelease of glutamate may protect the brain against bilirubin excitotoxicity. Riluzole is a prescription drug known for its antiglutamatergic function. This study was conducted in the rat's ventral cochlear nucleus, a structure highly sensitive to bilirubin toxicity, to find whether riluzole can be used to inhibit bilirubin toxicity. Experimental approach Electrophysiology changes were detected by perforated patch clamp technique. Calcium imaging using Rhod‐2‐ AM as an indicator was used to study the intracellular calcium. Cell apoptosis and necrosis were measured by PI /Hoechst staining. Key results In the absence of bilirubin, riluzole effectively decreased the frequency of spontaneous excitatory postsynaptic currents ( sEPSC s) and suppressed neuronal firing but did not change the amplitude of sEPSC and glutamate‐activated currents ( I G lu ). Moreover, riluzole inhibited bilirubin‐induced increases in the frequency of sEPSC and neuronal firing. Riluzole could prevent the bilirubin‐induced increase in intracellular calcium, mediated by AMPA and NMDA receptors. Furthermore, riluzole significantly reduced bilirubin‐induced cell death. Conclusions and implications These data suggest that riluzole can protect neurons in the ventral cochlear nucleus from bilirubin‐induced hyperexcitation and excitotoxicity through reducing presynaptic glutamate release.

Riluzole

Excitotoxicity

Ototoxicity

Neurotoxicity

10.1111/cns.12355

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Citations (13)

Prevalence of High Jugular Bulb across Different Stages of Adulthood in A Chinese Population

Aging and Disease (2020)

Jingjing Wang Yanmei Feng Hui Wang Chunyan Li Yaqin Wu

Pulsatile tinnitus, ear fullness, vertigo, hearing disorders, and vestibular dysfunction have been found to be related to high jugular bulb. Anatomical variation in this region also affects surgical planning and approaches. Therefore, knowledge on the detailed anatomy of the high jugular bulb is critical for middle ear and lateral skull base surgery. Prevalence of high jugular bulb is uncertain as data are usually derived from temporal bone specimens and patient reports from hospitals. Therefore, a community-based epidemiological study is necessary to understand the significance of high jugular bulb anatomy. Here, we report a cross-sectional study to characterize the prevalence of high jugular bulb and jugular bulb size using a 3.0 T magnetic resonance imaging. Furthermore, we studied the relationship between the prevalence of high jugular bulb and age-related changes. We enrolled 4539 permanent residents (9078 ears) from two communities in the Shanghai region who underwent magnetic resonance imaging between 2007 and 2011. We divided participants into four subgroups according to age: 35-44 (early middle age), 45-54 (middle age), 55-64 (late middle age), and 65-75 (late adulthood) years. We found that the overall prevalence of high jugular bulb was 14.5% in a Chinese population. There was a higher prevalence of high jugular bulb on the right side and especially in women (both p < 0.001). The occurrence of high jugular bulb was higher in the early middle age group and gradually decreased with age, but was still present in the late adulthood group (p = 0.039). These findings provide useful information on the prevalence of high jugular bulb in a Chinese population and the distribution in age groups, suggesting that high jugular bulb should be considered, even in those without ear disorders. This work serves as a foundation for further research on the relationship between jugular bulb changes and disease symptoms.

10.14336/ad.2020.0215

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Citations (15)

Interfacing Perforated Eardrums with Graphene‐Based Membranes for Broadband Hearing Recovery

Advanced Healthcare Materials (2022)

Chunyan Li Zhiyuan Xiong Lei Zhou Weiluo Huang Yu‐Shi He

Eardrum perforation and associated hearing loss is a global health problem. Grafting perforated eardrum with autologous tissues in clinic can restore low-frequency hearing but often leaves poor recovery of high-frequency hearing. In this study, the potential of incorporating a thin multilayered graphene membrane (MGM) into the eardrum for broadband hearing recovery in rats is examined. The MGM shows good biocompatibility and biostability to promote the growth of eardrum cells in a regulated manner with little sign of tissue rejection and inflammatory response. After three weeks of implantation, the MGM is found to be encapsulated by a thin layer of newly grown tissue on both sides without a significant folded overgrowth that is often seen in natural healing. The perforation is well sealed, and broadband hearing recovery (1-32 kHz) is enabled and maintained for at least 2 months. Mechanical simulations show that the high elastic modulus of MGM and thin thickness of the reconstructed eardrum play a critical role in the recovery of high-frequency hearing. This work demonstrates the promise of the use of MGM as a functional graft for perforated eardrum to recover hearing in the broadband frequency region and suggests a new acoustics-related medical application for graphene-related 2D materials.

Perforation

10.1002/adhm.202201471

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Citations (6)

Self-deflecting plasmonic lattice solitons and surface modes in chirped plasmonic arrays

Optics Letters (2015)

Chunyan Li Ran Cui Fangwei Ye Yaroslav V. Kartashov Lluís Torner

We show that chirped metal-dielectric waveguide arrays with focusing cubic nonlinearity can support plasmonic lattice solitons that undergo self-deflection in the transverse plane. Such lattice solitons are deeply-subwavelength self-sustained excitations, although they cover several periods of the array. Upon propagation,the excitations accelerate in the transverse plane and follow trajectories curved in the direction in which the separation between neighboring metallic layers decreases, a phenomenon that yields considerable deflection angles. The deflection angle can be controlled by varying the array chirp. We also reveal the existence of surface modes at the boundary of truncated plasmonic chirped arraythat form even in the absence of nonlinearity.

Chirp

Lattice (music)

10.1364/ol.40.000898

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Citations (8)