Functional connectivity changes in infants with varying degrees of unilateral hearing loss.

It has been proved that unilateral hearing loss (UHL) can cause functional connectivity alterations in adults. However, the mechanism of the human brain coping with the challenge of unilateral hearing deprivation at very early developmental phases remains poorly understood. Here, we performed a resting-state functional near-infrared spectroscopy (fNIRS) study on 3- to 10-month-old infants with varying degrees of unilateral hearing loss to investigate the effect of unilateral auditory deprivation in infants. Using network-based statistics, increased functional connectivity was observed in single-sided deafness (SSD) compared with normal hearing infants, and the right middle temporal gyrus was the most involved nodes. In addition, changes in cortical function in infants were related to the degree of hearing loss, with significantly increased functional connectivity in infants with severe to profound unilateral hearing loss compared with the ones with mild to moderate. Moreover, more significant cortical functional recombination changes were found in right-SSD than in left-SSD infants. For the first time, our study provides evidence for the effects of unilateral hearing deprivation on the early cortical development of the human brain, which would also act as a reference for intervention decisions in children with unilateral hearing loss in clinical settings.

Prediction of Nucleophilicity and Electrophilicity Based on a Machine-Learning Approach.

Nucleophilicity and electrophilicity dictate the reactivity of polar organic reactions. In the past decades, Mayr et al. established a quantitative scale for nucleophilicity (N) and electrophilicity (E), which proved to be a useful tool for the rationalization of chemical reactivity. In this study, a holistic prediction model was developed through a machine-learning approach. rSPOC, an ensemble molecular representation with structural, physicochemical and solvent features, was developed for this purpose. With 1115 nucleophiles, 285 electrophiles, and 22 solvents, the dataset is currently the largest one for reactivity prediction. The rSPOC model trained with the Extra Trees algorithm showed high accuracy in predicting Mayr's N and E parameters with R2 of 0.92 and 0.93, MAE of 1.45 and 1.45, respectively. Furthermore, the practical applications of the model, for instance, nucleophilicity prediction of NADH, NADPH and a series of enamines showed potential in predicting molecules with unknown reactivity within seconds. An online prediction platform (http://isyn.luoszgroup.com/) was constructed based on the current model, which is available free to the scientific community.

An Ensemble Structure and Physicochemical (SPOC) Descriptor for Machine-Learning Prediction of Chemical Reaction and Molecular Properties.

Feature representations, or descriptors, are machines' chemical language that largely shapes the prediction capability, generalizability and interpretability of machine learning models. To develop a generally applicable descriptor is highly warranted for chemists to deal with conventional prediction tasks in the context of sparsely distributed and small datasets. Inspired by the chemist's vision on molecules, we presented herein an ensemble descriptor, SPOC, curated on the principles of physical organic chemistry that integrates Structure and Physicochemical property (SPOC) of a molecule. SPOC could be readily constructed by combining molecular fingerprints, representing the structure of a given molecule, and molecular physicochemical properties extracted from RDKit or Mordred molecular descriptors. The applicability of SPOC was fully surveyed in a range of well-structured chemical databases with machine learning tasks varying from regression to classifications.

Modification of an engineered Escherichia coli by a combinatorial strategy to improve 3,4-dihydroxybutyric acid production.

OBJECTIVES: 3,4-Dihydroxybutyric acid (3,4-DHBA) is a multifunctional C4 platform compound widely used for the synthesis of various materials, including pharmaceuticals. Although, a biosynthetic pathway for 3,4-DHBA production has been developed, its low yield still precludes large-scale use. Here, a heterologous four-step biosynthetic pathway was established in recombinant Escherichia coli (E. coli) using a combinatorial strategy. RESULTS: Several aldehyde dehydrogenases (ALDHs) were screened, using in vitro enzyme assays, to identify suitable catalysts for the dehydrogenation of 3,4-dihydroxybutanal (3,4-DHB) to 3,4-DHBA. A pathway containing glucose dehydrogenase (BsGDH) from Bacillus subtilis, D-xylonate dehydratase (YagF) from E. coli, benzoylformate decarboxylase (PpMdlC) from Pseudomonas putida and ALDH was introduced into E. coli, generating 3.04 g/L 3,4-DHBA from D-xylose (0.190 g 3,4-DHBA/g D-xylose). Disruption of competing pathways by deleting xylA, ghrA, ghrB and adhP contributed to an 87% increase in 3,4-DHBA accumulation. Expression of a fusion construct containing PpMdlC and YagF enhanced the 3,4-DHBA titer, producing the highest titer and yield reported thus far (7.71 g/L; 0.482 g 3,4-DHBA/g D-xylose). CONCLUSIONS: These results showed that deleting genes from competing pathways and constructing fusion proteins significantly improved the titer and yield of 3,4-DHBA in engineered E. coli.

3-Benzoylisoxazolines by 1,3-Dipolar Cycloaddition: Chloramine-T-Catalyzed Condensation of α-Nitroketones with Dipolarophiles.

In this study, 3-benzoylisoxazolines were synthesized by reacting alkenes with various α-nitroketones using chloramine-T as the base. The scope of α-nitroketones and alkenes is extensive, including different alkenes and alkynes to form various isoxazolines and isoxazoles. The use of chloramine-T, as the low-cost, easily handled, moderate base for 1,3-dipolar cycloaddition is attractive.

Prevalence of human papillomavirus genotypes and precancerous cervical lesions in a screening population in Beijing, China: analysis of results from China's top 3 hospital, 2009-2019.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Early detection and diagnosis play an important role in secondary prevention of cervical cancer. This study aims to provide more information to develop an effective strategy for the prevention and control of cervical cancer in northern China. METHODS: A retrospective single-centre descriptive cross-sectional study was conducted in Chinese PLA General Hospital located in Beijing, covering the period from January 2009 to June 2019. The patients who underwent a polymerase chain reaction (PCR)-based HPV genotyping test and cervical pathological diagnosis were included. Furthermore, we limited the interval between the two examination within 180 days for the purpose of making sure their correlation to analyse their relationship. Moreover, the relationship between different cervical lesions and age as well as single/multiple HPV infection was assessed. RESULTS: A total of 3134 patients were eligible in this study after HPV genotyping test and pathological diagnosis. Most of the patients (95%) were from northern China. Among the patients, 1745(55.68%) had high-grade squamous intraepithelial neoplasia (HSIL), 1354 (43.20%) had low-grade squamous intraepithelial neoplasia (LSIL) and 35 (1.12%) were Normal. The mean age was 42.06 ± 10.82(range, 17-79 years). The women aged 35-49 years accounted for the highest incidence rate. The top five most commonly identified HPV genotypes in each lesion class were as follows: HPV16, 58, 52, 31 and 51 in the class of HSIL; HPV16, 52, 58, 56 and 51 in the class of LSIL; HPV16, 31, 6,11, 52 and 58 in the class of normal. The frequencies of HPV single genotype infection and multiple genotypes infection were 55.26 and 34.18%, respectively. There was no difference in the attributable proportions of multiple genotypes infection amongst HSIL, LSIL and Normal. CONCLUSIONS: In Northern China, HPV16 was the most dominant genotype in the patients with pathological examination. The peak age of the onset of HSIL was between 35 and 49 years of age. Infection with multiple HPV genotypes did not increase the risk of HSIL. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

Holistic Prediction of the pKa in Diverse Solvents Based on a Machine-Learning Approach.

While many approaches to predict aqueous pKa values exist, the fast and accurate prediction of non-aqueous pKa values is still challenging. Based on the iBonD experimental pKa database (39 solvents), a holistic pKa prediction model was established using machine learning. Structural and physical-organic-parameter-based descriptors (SPOC) were introduced to represent the electronic and structural features of the molecules. The models trained with a neural network or the XGBoost algorithm showed the best prediction performance with a low MAE value of 0.87 pKa units. The approach allows a comprehensive mapping of all possible pKa correlations between different solvents and it was validated by predicting the aqueous pKa and micro-pKa of pharmaceutical molecules and pKa values of organocatalysts in DMSO and MeCN with high accuracy. An online prediction platform was constructed based on the current model, which can provide pKa prediction for different types of X-H acidity in the most commonly used solvents.

Selective Recovery of Battery-Grade Li2CO3 from Spent NCM Cathode Materials Using a One-Step Method of CO2 Carbonation Recovery Without Acids or Bases.

The recovery of spent lithium-ion batteries by traditional acid leaching is limited by serious pollution, complicated technology, and the low purity of Li2CO3. To address the problems of the traditional acid leaching process and increasing demand for decarbonization, a technique for the selective carbonation leaching of Li and the recovery of battery-grade Li2CO3 by a simple concentration precipitation process without acids or bases was developed. The coupling of CO2 and reducing agents could effectively promote the precipitation of MCO3 (M=Ni/Co/Mn) and the selective leaching of Li by decreasing the reducing capability needed for transition metals and decreasing the pH of the solution. The optimal selective leaching process of Li was obtained under 1 MPa CO2 with 20 g/L Na2S2O3 at an L/S ratio of 30 mL/g for 1.5 h. FT-IR, XRD, ICP-MS and other methods were used to reveal the multiphase interfacial reaction mechanism of the carbonation reduction of layered cathode materials, which indicated that the reducing agent Na2S2O3 could promote lattice distortion of the cathode materials and effective separation of Li. In summary, a green and economical method for the selective recovery of battery-grade Li2CO3 using a one-step method of CO2 carbonation recovery in a near-neutral environment was proposed.

Genome-wide analysis of small RNAs reveals eight fiber elongation-related and 257 novel microRNAs in elongating cotton fiber cells.

BACKGROUND: MicroRNAs (miRNAs) and other types of small regulatory RNAs play critical roles in the regulation of gene expression at the post-transcriptional level in plants. Cotton is one of the most economically important crops, but little is known about the roles of miRNAs during cotton fiber elongation. RESULTS: Here, we combined high-throughput sequencing with computational analysis to identify small RNAs (sRNAs) related to cotton fiber elongation in Gossypium hirsutum L. (G. hirsutum). The sequence analysis confirmed the expression of 79 known miRNA families in elongating fiber cells and identified 257 novel miRNAs, primarily derived from corresponding specific loci in the Gossypium raimondii Ulbr. (G. raimondii) genome. Furthermore, a comparison of the miRNAomes revealed that 46 miRNA families were differentially expressed throughout the elongation period. Importantly, the predicted and experimentally validated targets of eight miRNAs were associated with fiber elongation, with obvious functional relationships with calcium and auxin signal transduction, fatty acid metabolism, anthocyanin synthesis and the xylem tissue differentiation. Moreover, one tasiRNA was also identified, and its target, ARF4, was experimentally validated in vivo. CONCLUSION: This study not only facilitated the discovery of 257 novel low-abundance miRNAs in elongating cotton fiber cells but also revealed a potential regulatory network of nine sRNAs important for fiber elongation. The identification and characterization of miRNAs in elongating cotton fiber cells might promote the further study of fiber miRNA regulation mechanisms and provide insight into the importance of miRNAs in cotton.

The Spherical Evolutionary Multi-Objective (SEMO) Algorithm for Identifying Disease Multi-Locus SNP Interactions.

Single-nucleotide polymorphisms (SNPs), as disease-related biogenetic markers, are crucial in elucidating complex disease susceptibility and pathogenesis. Due to computational inefficiency, it is difficult to identify high-dimensional SNP interactions efficiently using combinatorial search methods, so the spherical evolutionary multi-objective (SEMO) algorithm for detecting multi-locus SNP interactions was proposed. The algorithm uses a spherical search factor and a feedback mechanism of excellent individual history memory to enhance the balance between search and acquisition. Moreover, a multi-objective fitness function based on the decomposition idea was used to evaluate the associations by combining two functions, K2-Score and LR-Score, as an objective function for the algorithm's evolutionary iterations. The performance evaluation of SEMO was compared with six state-of-the-art algorithms on a simulated dataset. The results showed that SEMO outperforms the comparative methods by detecting SNP interactions quickly and accurately with a shorter average run time. The SEMO algorithm was applied to the Wellcome Trust Case Control Consortium (WTCCC) breast cancer dataset and detected two- and three-point SNP interactions that were significantly associated with breast cancer, confirming the effectiveness of the algorithm. New combinations of SNPs associated with breast cancer were also identified, which will provide a new way to detect SNP interactions quickly and accurately.

Correlation between cortical auditory evoked potential and auditory speech performance in children with cochlear implants.

OBJECTIVES: This study aimed to explore the correlation between the characteristics of cortical auditory evoked potential (CAEP) of children with cochlear implants (CIs) and auditory and speech rehabilitation performance by an objective evaluation technique and subjective auditory and speech skills measurements. METHODS: All participants were recruited from Beijing Children's Hospital, Beijing, China. 19 children with CIs had their responses to the CAEP and MMN recorded. The LittlEARs® Auditory Questionnaire (LEAQ), Categories of Auditory Performance (CAP), Speech Intelligibility Rating Scale (SIR), Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS), and Meaningful Use of Speech Scale (MUSS) measures were taken to assess the children's speech and hearing abilities. RESULTS: P1 and MMN of CAEP were negatively related to the duration of CI usage. The duration of CI usage and scores of auditory-verbal assessment questionnaires all showed significant relationships. Additionally, scores of these questionnaires were significantly inversely associated with the latency of P1 and MMN. CONCLUSION: P1 and MMN could be used as objective methods to evaluate the effectiveness of hearing and speech rehabilitation in children with CIs. In particular to those who cannot give effectively feedback of auditory and verbal effects, these methods might have a certain guiding significance.

Enhancement of the degradation capacity of IsPETase for PET plastic degradation by protein engineering.

The enormous waste of polyethylene terephthalate (PET) plastic has a great negative impact on the ecological environment because of its chemical inertia. To reduce the environmental threat posed by PET plastic, researchers gradually concentrate on the biodegradation of PET plastic. In this study, DuraPETaseN233C/S282C/H214S/S245R (DuraPETase-4M) was designed through protein engineering, which can be used to improve the efficiency of PET plastic biodegradation. Based on the DuraPETase, a pair of disulfide bonds (N233C/S282C) was added to improve the thermal stability. Meanwhile, the key region flexibility adjustment (H214S) was proposed to enhance the biodegradation capacity of PET plastic. Additionally, protein surface electrostatic charge optimization (S245R) was adopted to improve the binding ability between enzyme and PET plastic. Based on molecular dynamic simulations (MDs), the rationality of the design was further verified. This study provides a strategy for obtaining high-efficiency PET degradation mutants and a new possibility of environmentally friendly plastic degradation.

A water-dependent reversible photoacidity strategy for cancer treatment.

In the reported mechanisms of reversible photoacidity, protons were dissociated from compounds which contained hydroxyl, indazole or formed hydroxyl via intramolecular hydrogen abstraction under irradiation. Herein, a water-dependent reversible photoacidity (W-RPA) mechanism mediated by a thiadiazoloquinoxaline compound (TQs-Th-PEG5) has been found, in which the proton is not dissociated from TQs-Th-PEG5 itself but from a water locked by TQs-Th-PEG5 under the irradiation of a 660 nm laser. After turning off the laser, the produced acid will disappear quickly. This process is repeatable with no consumption of TQs-Th-PEG5. More importantly, water is indispensable. Furthermore, it is confirmed that there is no other element involved in the process except TQs-Th-PEG5, light and water. Excitingly, W-RPA therapy mediated by TQs-Th-PEG5 nanoparticle exhibits remarkable antitumor effect both in vitro and in vivo, especially in hypoxic tumors with diameter larger than 10 mm owing to its oxygen-independent feature. This study not only discovers a W-RPA mechanism but also provides a novel phototherapy strategy for cancer treatment.

In vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® for cancer treatment.

BACKGROUND: Photodynamic therapy (PDT) has been approved for the clinical treatment of cancers. Photosensitizer (PS) is a crucial element of PDT. In the current study, in vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® was performed. METHODS: The physicochemical characteristics of KAE® were compared with chlorin e6. The intracellular distribution of KAE® in HeLa cells was observed by laser scanning confocal microscopy. Reactive oxygen species (ROS) generation was detected through a 2', 7-dichlorodihydrofluorescein diacetate probe. The pharmacokinetics of KAE® was studied in mice. The photodynamic activities of KAE® and porphyrin based PSs were compared both in vitro and in vivo. The biosafety of KAE® in mice was evaluated by pathological section observation, blood routine examination and biochemistry assays. RESULTS: KAE® was readily dissolved in an aqueous solvent in a clinically acceptable concentration and showed a strong absorption at around 660 nm. Most of KAE® was located in the mitochondria of the tumor cells. Compared with hematoporphyrin derivative and 5-aminolevulinic acid, KAE® displayed a higher efficiency in cell killing. Furthermore, it could be completely eliminated from mouse body in 2 days. KAE® had no toxicity to mice under the tested dosage. CONCLUSIONS: Our results suggested that KAE® is an effective and safe PS for PDT in cancer therapy and has a promising prospect for clinical application.

The stability and spicy taste masking effect of capsaicin loaded α-lactalbumin micelles formulated in defatted cheese.

Capsaicin (Cap) is a promising bioactive compound having many health-promoting benefits. However, it is difficult to be applied in food due to its poor aqueous solubility, low stability and bioavailability. Besides, its strong spicy taste and irritation to the gastrointestinal tract further limit the application of Cap in food. To solve this problem, Cap was loaded into a self-assembled nanocarrier formed by partial hydrolysis of α-lactalbumin (α-lac). The Cap was successfully loaded into the 21.2 nm micelles with a loading capacity of 123.4 ± 6.1 mg g-1. The aqueous solubility was greatly improved. Besides, nanomicelles also showed intestinal responsive release behavior. The in vivo bioavailability of Cap was improved by nanomicelles for 3.1 times. The Cap loaded nanomicelles in the milk system showed good colloidal stability compared to solely Cap in milk. Therefore, the Cap loaded nanocarriers were added into the de-fatted milk to prepare de-fatted cheese with an acceptable spicy flavor. The nanocarriers were clearly captured in the cheese casein network as confirmed by confocal microscopy. The sensory evaluation results showed the spicy taste of capsaicin was reduced in the nanomicelle system and further reduced in the nanomicelle-cheese systems. We postulated that it might be due to the nanomicelles reducing the contact of capsaicin with sensory neurons in the tongue thus masking the spicy taste. The cheese casein network structure further masked their contact. The above results indicated that Cap embedding via α-lac nanocarriers was feasible for masking their spicy taste and applying Cap to food systems such as milk and cheese.

Auditory and verbal skills development post-cochlear implantation in Mandarin children with auditory neuropathy: a follow-up study.

BACKGROUND: Cochlear implant (CI) is commonly used as one of the interventions in auditory neuropathy (AN) children. However, there are limited studies regarding the efficiency of CI in AN children. OBJECTIVE: This study aimed to compare the auditory and verbal skills development between the AN and typically developing (TD) children with CI. METHODS: The follow-up study compared the post-CI scores of questionnaires of AN and TD children about auditory and verbal skills development at 0, 1, 2, 3, 6, 9, 12, and 18 months of CI use. RESULTS: The results of auditory perception in AN and TD groups showed a significant improvement after first 3 months. Furthermore, the score was significantly lower in AN group after 18 months of CI use. The results of verbal skills in AN group showed a progressive trend after 9 months of CI use. Besides, the scores were significantly lower in AN group after 12 months of CI use. CONCLUSION AND SIGNIFICANCE: The auditory perception development in AN children with CI was rapidly improved during first 3 months, and verbal skills showed a trend of improvement after 9 months of CI use. However, the differences in auditory and verbal skills between AN and TD groups increased over time.

Investigation of novel de novo KCNC2 variants causing severe developmental and early-onset epileptic encephalopathy.

Purpose The voltage-gated potassium channel Kv3.2, encoded by KCNC2, facilitates fast-spiking GABAergic interneurons to fire action potentials at high frequencies. It is pivotal to maintaining excitation/inhibition balance in mammalian brains. This study identified two novel de novo KCNC2 variants, p.Pro470Ser (P470S) and p.Phe382Leu (F382L), in patients with early onset developmental and epileptic encephalopathy (DEE). Methods To examine the molecular basis of DEE, we studied the functional characteristics of variant channels using patch-clamp techniques and computational modeling. Results Whole-cell patch clamp recordings from infected HEK293 cells revealed that channel activation and deactivation kinetics strongly decreased in both Kv3.2 P470S and F382L variant channels. This decrease also occurred in Kv3.2 p.Val471Leu (V471L) channels, known to be associated with DEE. In addition, Kv3.2 F382L and V471L variants exhibited a significant increase in channel conductance and a ∼20 mV negative shift in the threshold for voltage-dependent activation. Simulations of model GABAergic interneurons revealed that all variants decreased neuronal firing frequency. Thus, the variants' net loss-of-function effects disinhibited neural networks. Conclusion Our findings provide compelling evidence supporting the role of KCNC2 as a disease-causing gene in human neurodevelopmental delay and epilepsy.

Interaction between human leukocyte antigen (HLA-C) and killer cell Ig-like receptors (KIR2DL) inhibits the cytotoxicity of natural killer cells in patients with hepatoblastoma.

Background: Hepatoblastoma (HB) is the most common liver malignancy in childhood with poor prognosis and lack of effective therapeutic targets. Single-cell transcriptome sequencing technology has been widely used in the study of malignant tumors, which can understand the tumor microenvironment and tumor heterogeneity. Materials and methods: Two children with HB and a healthy child were selected as the research subjects. Peripheral blood and tumor tissue were collected for single-cell transcriptome sequencing, and the sequencing data were compared and analyzed to describe the differences in the immune microenvironment between children with HB and normal children. Results: There were significant differences in the number and gene expression levels of natural killer cells (NK cells) between children with HB and normal children. More natural killer cells were seen in children with HB compared to normal control. KIR2DL were highly expressed in children with HB. Conclusion: Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMC) and tumor tissue from children with HB revealed that KIR2DL was significantly up-regulated in NK cells from children with HB. HLA-C molecules on the surface of tumor cells interact with inhibitory receptor KIR2DL on the surface of NK cells, inhibiting the cytotoxicity of NK cells, resulting in immune escape of tumors. Inhibitors of related immune checkpoints to block the interaction between HLA-C and KIR2DL and enhance the cytotoxicity of NK cells, which may be a new strategy for HB treatment.

Quantitative assessment of vascular features in port wine stains through optical coherence tomography angiography.

BACKGROUND: Vascular lesions such as port wine stains (PWS) lead to facial and psychological problems, which require careful and precise treatments. The key point of treating PWS is to selectively destroy the abnormal blood vessels. Hence, the in vivo monitoring of targeted vessels is crucial. Optical coherence tomography angiography (OCTA), an emerging label-free imaging tool, facilitates the evaluation of skin structure and vasculature at a high resolution. In this study, we utilised OCTA to capture the structural and vascular morphology in patients with PWS. Moreover, we quantitatively characterised the morphological features of different types of PWS. METHODS: This observational clinical study was conducted on 3 patients with flat PWS and 3 patients with thickened PWS. The age range was 4-27 years, and all of them had not received any treatment before this study. The OCTA images of the PWS lesions and contralateral skin were compared. Vascular morphology was characterized, and ectatic vessel depth was quantified according to the OCTA images. RESULTS: The blood vessels of the PWS lesions tend to had larger diameters and higher densities than those in the contralateral normal skin. The vessel diameters of PWS lesions were 73 ± 14 µm, with high heterogeneity ranging from 10 to >150 µm, however, the vessel diameters of normal skin were 28 ± 2 µm, ranging from 10 µm to 60 µm. In terms of different PWS lesions, the thickened type showed a trend of larger vessel diameter and higher density than those of the purplish red type. The ectatic vessels were located at the depth of 216 ± 13 µm in the PWS skin. CONCLUSIONS: OCTA can facilitate the in vivo three-dimensional visualization of structure and vasculature for PWS lesions. Various quantitative analysis parameters, such as vessel diameter, density, and depth, are typically measured using OCTA. This fact demonstrates the superior capability of OCTA for the precise and comprehensive assessment of PWS lesions.

Objective electroencephalography-based assessment for auditory rehabilitation of pediatric cochlear implant users.

The cochlear implant (CI) has an effective habilitation modality for hearing-impaired children by promoting sound perception, vocalization, and language ability. However, the major challenge that remained was the lack of assessment standards for pediatric CI users, especially prelingually deaf children, to evaluate hearing rehabilitation effectiveness. In the present study, we conducted an oddball paradigm with stimuli varying in pure-tone, syllable, and tonal sounds. After implantation, we utilized cortical auditory evoked potential (CAEP) and mismatch negativity (MMN) to obtain time-domain analysis; meanwhile, the source localization was investigated to obtain spatial accuracy of the plasticity in the auditory cortex. P1 started to emerge at the third month after implantation, but its peak level was not significant until the sixth month. The temporal lobe was activated between the third and sixth months after implantation. The MMN waveform was basically normal approximately after 12 months. These results suggest that the auditory system goes through a critical period of rapid development between three and six months and enters a maturation period after 12 months. This work indicates that CAEPs are more suitable for assessing the early auditory system reconstruction, while MMN performs better in evaluating the advanced auditory function. Furthermore, source localization has proven to be an efficient tool in exploring auditory cortex plasticity, especially for pediatric CI users.