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1. Language Model Can Listen While Speaking

Author

Ma, Ziyang, Song, Yakun, Du, Chenpeng, Cong, Jian, Chen, Zhuo, Wang, Yuping, Wang, Yuxuan, and Chen, Xie

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Computer Science - Human-Computer Interaction, Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing
Abstract

Dialogue serves as the most natural manner of human-computer interaction (HCI). Recent advancements in speech language models (SLM) have significantly enhanced speech-based conversational AI. However, these models are limited to turn-based conversation, lacking the ability to interact with humans in real-time spoken scenarios, for example, being interrupted when the generated content is not satisfactory. To address these limitations, we explore full duplex modeling (FDM) in interactive speech language models (iSLM), focusing on enhancing real-time interaction and, more explicitly, exploring the quintessential ability of interruption. We introduce a novel model design, namely listening-while-speaking language model (LSLM), an end-to-end system equipped with both listening and speaking channels. Our LSLM employs a token-based decoder-only TTS for speech generation and a streaming self-supervised learning (SSL) encoder for real-time audio input. LSLM fuses both channels for autoregressive generation and detects turn-taking in real time. Three fusion strategies -- early fusion, middle fusion, and late fusion -- are explored, with middle fusion achieving an optimal balance between speech generation and real-time interaction. Two experimental settings, command-based FDM and voice-based FDM, demonstrate LSLM's robustness to noise and sensitivity to diverse instructions. Our results highlight LSLM's capability to achieve duplex communication with minimal impact on existing systems. This study aims to advance the development of interactive speech dialogue systems, enhancing their applicability in real-world contexts., Comment: Demo can be found at https://ddlbojack.github.io/LSLM

Published
2024

2. Seed-TTS: A Family of High-Quality Versatile Speech Generation Models

Author

Anastassiou, Philip, Chen, Jiawei, Chen, Jitong, Chen, Yuanzhe, Chen, Zhuo, Chen, Ziyi, Cong, Jian, Deng, Lelai, Ding, Chuang, Gao, Lu, Gong, Mingqing, Huang, Peisong, Huang, Qingqing, Huang, Zhiying, Huo, Yuanyuan, Jia, Dongya, Li, Chumin, Li, Feiya, Li, Hui, Li, Jiaxin, Li, Xiaoyang, Li, Xingxing, Liu, Lin, Liu, Shouda, Liu, Sichao, Liu, Xudong, Liu, Yuchen, Liu, Zhengxi, Lu, Lu, Pan, Junjie, Wang, Xin, Wang, Yuping, Wang, Yuxuan, Wei, Zhen, Wu, Jian, Yao, Chao, Yang, Yifeng, Yi, Yuanhao, Zhang, Junteng, Zhang, Qidi, Zhang, Shuo, Zhang, Wenjie, Zhang, Yang, Zhao, Zilin, Zhong, Dejian, and Zhuang, Xiaobin

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Sound
Abstract

We introduce Seed-TTS, a family of large-scale autoregressive text-to-speech (TTS) models capable of generating speech that is virtually indistinguishable from human speech. Seed-TTS serves as a foundation model for speech generation and excels in speech in-context learning, achieving performance in speaker similarity and naturalness that matches ground truth human speech in both objective and subjective evaluations. With fine-tuning, we achieve even higher subjective scores across these metrics. Seed-TTS offers superior controllability over various speech attributes such as emotion and is capable of generating highly expressive and diverse speech for speakers in the wild. Furthermore, we propose a self-distillation method for speech factorization, as well as a reinforcement learning approach to enhance model robustness, speaker similarity, and controllability. We additionally present a non-autoregressive (NAR) variant of the Seed-TTS model, named $\text{Seed-TTS}_\text{DiT}$, which utilizes a fully diffusion-based architecture. Unlike previous NAR-based TTS systems, $\text{Seed-TTS}_\text{DiT}$ does not depend on pre-estimated phoneme durations and performs speech generation through end-to-end processing. We demonstrate that this variant achieves comparable performance to the language model-based variant and showcase its effectiveness in speech editing. We encourage readers to listen to demos at \url{https://bytedancespeech.github.io/seedtts_tech_report}.

Published
2024

3. U-Style: Cascading U-nets with Multi-level Speaker and Style Modeling for Zero-Shot Voice Cloning

Author

Li, Tao, Wang, Zhichao, Zhu, Xinfa, Cong, Jian, Tian, Qiao, Wang, Yuping, and Xie, Lei

Subjects
Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing
Abstract

Zero-shot speaker cloning aims to synthesize speech for any target speaker unseen during TTS system building, given only a single speech reference of the speaker at hand. Although more practical in real applications, the current zero-shot methods still produce speech with undesirable naturalness and speaker similarity. Moreover, endowing the target speaker with arbitrary speaking styles in the zero-shot setup has not been considered. This is because the unique challenge of zero-shot speaker and style cloning is to learn the disentangled speaker and style representations from only short references representing an arbitrary speaker and an arbitrary style. To address this challenge, we propose U-Style, which employs Grad-TTS as the backbone, particularly cascading a speaker-specific encoder and a style-specific encoder between the text encoder and the diffusion decoder. Thus, leveraging signal perturbation, U-Style is explicitly decomposed into speaker- and style-specific modeling parts, achieving better speaker and style disentanglement. To improve unseen speaker and style modeling ability, these two encoders conduct multi-level speaker and style modeling by skip-connected U-nets, incorporating the representation extraction and information reconstruction process. Besides, to improve the naturalness of synthetic speech, we adopt mean-based instance normalization and style adaptive layer normalization in these encoders to perform representation extraction and condition adaptation, respectively. Experiments show that U-Style significantly surpasses the state-of-the-art methods in unseen speaker cloning regarding naturalness and speaker similarity. Notably, U-Style can transfer the style from an unseen source speaker to another unseen target speaker, achieving flexible combinations of desired speaker timbre and style in zero-shot voice cloning.

Published
2023

4. DiCLET-TTS: Diffusion Model based Cross-lingual Emotion Transfer for Text-to-Speech -- A Study between English and Mandarin

Author

Li, Tao, Hu, Chenxu, Cong, Jian, Zhu, Xinfa, Li, Jingbei, Tian, Qiao, Wang, Yuping, and Xie, Lei

Subjects
Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing
Abstract

While the performance of cross-lingual TTS based on monolingual corpora has been significantly improved recently, generating cross-lingual speech still suffers from the foreign accent problem, leading to limited naturalness. Besides, current cross-lingual methods ignore modeling emotion, which is indispensable paralinguistic information in speech delivery. In this paper, we propose DiCLET-TTS, a Diffusion model based Cross-Lingual Emotion Transfer method that can transfer emotion from a source speaker to the intra- and cross-lingual target speakers. Specifically, to relieve the foreign accent problem while improving the emotion expressiveness, the terminal distribution of the forward diffusion process is parameterized into a speaker-irrelevant but emotion-related linguistic prior by a prior text encoder with the emotion embedding as a condition. To address the weaker emotional expressiveness problem caused by speaker disentanglement in emotion embedding, a novel orthogonal projection based emotion disentangling module (OP-EDM) is proposed to learn the speaker-irrelevant but emotion-discriminative embedding. Moreover, a condition-enhanced DPM decoder is introduced to strengthen the modeling ability of the speaker and the emotion in the reverse diffusion process to further improve emotion expressiveness in speech delivery. Cross-lingual emotion transfer experiments show the superiority of DiCLET-TTS over various competitive models and the good design of OP-EDM in learning speaker-irrelevant but emotion-discriminative embedding., Comment: accepted by TASLP

Published
2023

5. Extensive genomic study characterizing three Paracoccaceae populations and revealing Pseudogemmobacter lacusdianii sp. nov. and Paracoccus broussonetiae sp. nov.

Author

Yang Deng, Cong-Jian Li, Jing Zhang, Wei-Hong Liu, Li-Yan Yu, and Yu-Qin Zhang

Subjects
Paracoccaceae, genome, Pseudogemmobacter lacusdianii, Paracoccus broussonetiae, 5-aminolevulinic acid, Microbiology, QR1-502
Abstract

ABSTRACT Bacteria within the family Paracoccaceae show promising potential for applications in various fields, garnering significant research attention. Three Gram stain-negative bacteria, strains CPCC 101601T, CPCC 101403T, and CPCC 100767, were isolated from diverse environments: freshwater, rhizosphere soil of Broussonetia papyrifera, and the phycosphere, respectively. Analysis of their 16S rRNA gene sequences, compared with those in the GenBank database, indicated that they belong to the family Paracoccaceae, with nucleotide similarities of 92.5%–99.9% to all of the Paracoccaceae members with valid taxonomic names. Phylogenetic studies based on 16S rRNA gene and whole-genome sequences identified CPCC 101601T as a member of the genus Pseudogemmobacter, CPCC 101403T belonging to the genus Paracoccus, and CPCC 100767 as part of the genus Gemmobacter. Notably, genomic analysis using average nucleotide identity (ANI;

Published
2024
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6. DSPGAN: a GAN-based universal vocoder for high-fidelity TTS by time-frequency domain supervision from DSP

Author

Song, Kun, Zhang, Yongmao, Lei, Yi, Cong, Jian, Li, Hanzhao, Xie, Lei, He, Gang, and Bai, Jinfeng

Subjects
Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing
Abstract

Recent development of neural vocoders based on the generative adversarial neural network (GAN) has shown obvious advantages of generating raw waveform conditioned on mel-spectrogram with fast inference speed and lightweight networks. Whereas, it is still challenging to train a universal neural vocoder that can synthesize high-fidelity speech from various scenarios with unseen speakers, languages, and speaking styles. In this paper, we propose DSPGAN, a GAN-based universal vocoder for high-fidelity speech synthesis by applying the time-frequency domain supervision from digital signal processing (DSP). To eliminate the mismatch problem caused by the ground-truth spectrograms in the training phase and the predicted spectrograms in the inference phase, we leverage the mel-spectrogram extracted from the waveform generated by a DSP module, rather than the predicted mel-spectrogram from the Text-to-Speech (TTS) acoustic model, as the time-frequency domain supervision to the GAN-based vocoder. We also utilize sine excitation as the time-domain supervision to improve the harmonic modeling and eliminate various artifacts of the GAN-based vocoder. Experiments show that DSPGAN significantly outperforms the compared approaches and it can generate high-fidelity speech for various TTS models trained using diverse data., Comment: Accepted to ICASSP 2023

Published
2022

7. Robust MelGAN: A robust universal neural vocoder for high-fidelity TTS

Author

Song, Kun, Cong, Jian, Wang, Xinsheng, Zhang, Yongmao, Xie, Lei, Jiang, Ning, and Wu, Haiying

Subjects
Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing
Abstract

In current two-stage neural text-to-speech (TTS) paradigm, it is ideal to have a universal neural vocoder, once trained, which is robust to imperfect mel-spectrogram predicted from the acoustic model. To this end, we propose Robust MelGAN vocoder by solving the original multi-band MelGAN's metallic sound problem and increasing its generalization ability. Specifically, we introduce a fine-grained network dropout strategy to the generator. With a specifically designed over-smooth handler which separates speech signal intro periodic and aperiodic components, we only perform network dropout to the aperodic components, which alleviates metallic sounding and maintains good speaker similarity. To further improve generalization ability, we introduce several data augmentation methods to augment fake data in the discriminator, including harmonic shift, harmonic noise and phase noise. Experiments show that Robust MelGAN can be used as a universal vocoder, significantly improving sound quality in TTS systems built on various types of data., Comment: Accepted by ISCSLP 2022

Published
2022

8. Glow-WaveGAN 2: High-quality Zero-shot Text-to-speech Synthesis and Any-to-any Voice Conversion

Author

Lei, Yi, Yang, Shan, Cong, Jian, Xie, Lei, and Su, Dan

Subjects
Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing
Abstract

The zero-shot scenario for speech generation aims at synthesizing a novel unseen voice with only one utterance of the target speaker. Although the challenges of adapting new voices in zero-shot scenario exist in both stages -- acoustic modeling and vocoder, previous works usually consider the problem from only one stage. In this paper, we extend our previous Glow-WaveGAN to Glow-WaveGAN 2, aiming to solve the problem from both stages for high-quality zero-shot text-to-speech and any-to-any voice conversion. We first build a universal WaveGAN model for extracting latent distribution $p(z)$ of speech and reconstructing waveform from it. Then a flow-based acoustic model only needs to learn the same $p(z)$ from texts, which naturally avoids the mismatch between the acoustic model and the vocoder, resulting in high-quality generated speech without model fine-tuning. Based on a continuous speaker space and the reversible property of flows, the conditional distribution can be obtained for any speaker, and thus we can further conduct high-quality zero-shot speech generation for new speakers. We particularly investigate two methods to construct the speaker space, namely pre-trained speaker encoder and jointly-trained speaker encoder. The superiority of Glow-WaveGAN 2 has been proved through TTS and VC experiments conducted on LibriTTS corpus and VTCK corpus.

Published
2022

9. AdaVITS: Tiny VITS for Low Computing Resource Speaker Adaptation

Author

Song, Kun, Xue, Heyang, Wang, Xinsheng, Cong, Jian, Zhang, Yongmao, Xie, Lei, Yang, Bing, Zhang, Xiong, and Su, Dan

Subjects
Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing
Abstract

Speaker adaptation in text-to-speech synthesis (TTS) is to finetune a pre-trained TTS model to adapt to new target speakers with limited data. While much effort has been conducted towards this task, seldom work has been performed for low computational resource scenarios due to the challenges raised by the requirement of the lightweight model and less computational complexity. In this paper, a tiny VITS-based TTS model, named AdaVITS, for low computing resource speaker adaptation is proposed. To effectively reduce parameters and computational complexity of VITS, an iSTFT-based wave construction decoder is proposed to replace the upsampling-based decoder which is resource-consuming in the original VITS. Besides, NanoFlow is introduced to share the density estimate across flow blocks to reduce the parameters of the prior encoder. Furthermore, to reduce the computational complexity of the textual encoder, scaled-dot attention is replaced with linear attention. To deal with the instability caused by the simplified model, instead of using the original text encoder, phonetic posteriorgram (PPG) is utilized as linguistic feature via a text-to-PPG module, which is then used as input for the encoder. Experiment shows that AdaVITS can generate stable and natural speech in speaker adaptation with 8.97M model parameters and 0.72GFlops computational complexity., Comment: Accepted by ISCSLP 2022

Published
2022

10. NaturalSpeech: End-to-End Text to Speech Synthesis with Human-Level Quality

Author

Tan, Xu, Chen, Jiawei, Liu, Haohe, Cong, Jian, Zhang, Chen, Liu, Yanqing, Wang, Xi, Leng, Yichong, Yi, Yuanhao, He, Lei, Soong, Frank, Qin, Tao, Zhao, Sheng, and Liu, Tie-Yan

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Artificial Intelligence, Computer Science - Computation and Language, Computer Science - Machine Learning, Computer Science - Sound
Abstract

Text to speech (TTS) has made rapid progress in both academia and industry in recent years. Some questions naturally arise that whether a TTS system can achieve human-level quality, how to define/judge that quality and how to achieve it. In this paper, we answer these questions by first defining the human-level quality based on the statistical significance of subjective measure and introducing appropriate guidelines to judge it, and then developing a TTS system called NaturalSpeech that achieves human-level quality on a benchmark dataset. Specifically, we leverage a variational autoencoder (VAE) for end-to-end text to waveform generation, with several key modules to enhance the capacity of the prior from text and reduce the complexity of the posterior from speech, including phoneme pre-training, differentiable duration modeling, bidirectional prior/posterior modeling, and a memory mechanism in VAE. Experiment evaluations on popular LJSpeech dataset show that our proposed NaturalSpeech achieves -0.01 CMOS (comparative mean opinion score) to human recordings at the sentence level, with Wilcoxon signed rank test at p-level p >> 0.05, which demonstrates no statistically significant difference from human recordings for the first time on this dataset., Comment: 19 pages, 3 figures, 8 tables

Published
2022

11. VISinger: Variational Inference with Adversarial Learning for End-to-End Singing Voice Synthesis

Author

Zhang, Yongmao, Cong, Jian, Xue, Heyang, Xie, Lei, Zhu, Pengcheng, and Bi, Mengxiao

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Sound
Abstract

In this paper, we propose VISinger, a complete end-to-end high-quality singing voice synthesis (SVS) system that directly generates audio waveform from lyrics and musical score. Our approach is inspired by VITS, which adopts VAE-based posterior encoder augmented with normalizing flow-based prior encoder and adversarial decoder to realize complete end-to-end speech generation. VISinger follows the main architecture of VITS, but makes substantial improvements to the prior encoder based on the characteristics of singing. First, instead of using phoneme-level mean and variance of acoustic features, we introduce a length regulator and a frame prior network to get the frame-level mean and variance on acoustic features, modeling the rich acoustic variation in singing. Second, we further introduce an F0 predictor to guide the frame prior network, leading to stabler singing performance. Finally, to improve the singing rhythm, we modify the duration predictor to specifically predict the phoneme to note duration ratio, helped with singing note normalization. Experiments on a professional Mandarin singing corpus show that VISinger significantly outperforms FastSpeech+Neural-Vocoder two-stage approach and the oracle VITS; ablation study demonstrates the effectiveness of different contributions., Comment: 5 pages, ICASSP 2022

Published
2021

13. Glow-WaveGAN: Learning Speech Representations from GAN-based Variational Auto-Encoder For High Fidelity Flow-based Speech Synthesis

Author

Cong, Jian, Yang, Shan, Xie, Lei, and Su, Dan

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Sound
Abstract

Current two-stage TTS framework typically integrates an acoustic model with a vocoder -- the acoustic model predicts a low resolution intermediate representation such as Mel-spectrum while the vocoder generates waveform from the intermediate representation. Although the intermediate representation is served as a bridge, there still exists critical mismatch between the acoustic model and the vocoder as they are commonly separately learned and work on different distributions of representation, leading to inevitable artifacts in the synthesized speech. In this work, different from using pre-designed intermediate representation in most previous studies, we propose to use VAE combining with GAN to learn a latent representation directly from speech and then utilize a flow-based acoustic model to model the distribution of the latent representation from text. In this way, the mismatch problem is migrated as the two stages work on the same distribution. Results demonstrate that the flow-based acoustic model can exactly model the distribution of our learned speech representation and the proposed TTS framework, namely Glow-WaveGAN, can produce high fidelity speech outperforming the state-of-the-art GAN-based model., Comment: Accepted to INTERSPEECH 2021

Published
2021

14. Controllable Context-aware Conversational Speech Synthesis

Author

Cong, Jian, Yang, Shan, Hu, Na, Li, Guangzhi, Xie, Lei, and Su, Dan

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Sound
Abstract

In spoken conversations, spontaneous behaviors like filled pause and prolongations always happen. Conversational partner tends to align features of their speech with their interlocutor which is known as entrainment. To produce human-like conversations, we propose a unified controllable spontaneous conversational speech synthesis framework to model the above two phenomena. Specifically, we use explicit labels to represent two typical spontaneous behaviors filled-pause and prolongation in the acoustic model and develop a neural network based predictor to predict the occurrences of the two behaviors from text. We subsequently develop an algorithm based on the predictor to control the occurrence frequency of the behaviors, making the synthesized speech vary from less disfluent to more disfluent. To model the speech entrainment at acoustic level, we utilize a context acoustic encoder to extract a global style embedding from the previous speech conditioning on the synthesizing of current speech. Furthermore, since the current and previous utterances belong to the different speakers in a conversation, we add a domain adversarial training module to eliminate the speaker-related information in the acoustic encoder while maintaining the style-related information. Experiments show that our proposed approach can synthesize realistic conversations and control the occurrences of the spontaneous behaviors naturally., Comment: Accepted to INTERSPEECH 2021

Published
2021

15. Data Efficient Voice Cloning from Noisy Samples with Domain Adversarial Training

Author

Cong, Jian, Yang, Shan, Xie, Lei, Yu, Guoqiao, and Wan, Guanglu

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Sound
Abstract

Data efficient voice cloning aims at synthesizing target speaker's voice with only a few enrollment samples at hand. To this end, speaker adaptation and speaker encoding are two typical methods based on base model trained from multiple speakers. The former uses a small set of target speaker data to transfer the multi-speaker model to target speaker's voice through direct model update, while in the latter, only a few seconds of target speaker's audio directly goes through an extra speaker encoding model along with the multi-speaker model to synthesize target speaker's voice without model update. Nevertheless, the two methods need clean target speaker data. However, the samples provided by user may inevitably contain acoustic noise in real applications. It's still challenging to generating target voice with noisy data. In this paper, we study the data efficient voice cloning problem from noisy samples under the sequence-to-sequence based TTS paradigm. Specifically, we introduce domain adversarial training (DAT) to speaker adaptation and speaker encoding, which aims to disentangle noise from speech-noise mixture. Experiments show that for both speaker adaptation and encoding, the proposed approaches can consistently synthesize clean speech from noisy speaker samples, apparently outperforming the method adopting state-of-the-art speech enhancement module., Comment: Accepted to INTERSPEECH 2020

Published
2020

16. Anterograde Viral Tracer Herpes Simplex Virus 1 Strain H129 Transports Primarily as Capsids in Cortical Neuron Axons.

Author

Dong, Xiao, Zhou, Jing, Qin, Hai-Bin, Xin, Bo, Huang, Zhen-Li, Li, Yin-Yun, Zhao, Fei, Zhao, Cong-Jian, Liu, Jia-Jia, Luo, Min-Hua, Zeng, Wen-Bo, and Xu, Xiangmin

Subjects
HSV-1 strain H129, anterograde movement, anterograde transneuronal tracer, axonal transport, capsids, cortical neuron, dynein, kinesin-1, retrograde movement, virions, Animals, Axonal Transport, Axons, Capsid, Chlorocebus aethiops, Disease Models, Animal, Glycoproteins, Green Fluorescent Proteins, Herpes Simplex, Herpesvirus 1, Human, Kinesins, Mice, Mice, Inbred C57BL, Neurons, Vero Cells, Virion
Abstract

The features of herpes simplex virus 1 (HSV-1) strain 129 (H129), including natural neurotropism and anterograde transneuronal trafficking, make it a potential tool for anterograde neural circuitry tracing. Recently anterograde polysynaptic and monosynaptic tracers were developed from H129 and have been applied for the identification of novel connections and functions of different neural circuitries. However, how H129 viral particles are transported in neurons, especially those of the central nervous system, remains unclear. In this study, we constructed recombinant H129 variants with mCherry-labeled capsids and/or green fluorescent protein (GFP)-labeled envelopes and infected the cortical neurons to study axonal transport of H129 viral particles. We found that different types of viral particles were unevenly distributed in the nucleus, cytoplasm of the cell body, and axon. Most H129 progeny particles were unenveloped capsids and were transported as capsids rather than virions in the axon. Notably, capsids acquired envelopes at axonal varicosities and terminals where the sites forming synapses are connected with other neurons. Moreover, viral capsids moved more frequently in the anterograde direction in axons, with an average velocity of 0.62 ± 0.18 μm/s and maximal velocity of 1.80 ± 0.15 μm/s. We also provided evidence that axonal transport of capsids requires the kinesin-1 molecular motor. These findings support that H129-derived tracers map the neural circuit anterogradely and possibly transsynaptically. These data will guide future modifications and improvements of H129-based anterograde viral tracers.IMPORTANCE Anterograde transneuronal tracers derived from herpes simplex virus 1 (HSV-1) strain 129 (H129) are important tools for mapping neural circuit anatomic and functional connections. It is, therefore, critical to elucidate the transport pattern of H129 within neurons and between neurons. We constructed recombinant H129 variants with genetically encoded fluorescence-labeled capsid protein and/or glycoprotein to visualize viral particle movement in neurons. Both electron microscopy and light microscopy data show that H129 capsids and envelopes move separately, and notably, capsids are enveloped at axonal varicosity and terminals, which are the sites forming synapses to connect with other neurons. Superresolution microscopy-based colocalization analysis and inhibition of H129 particle movement by inhibitors of molecular motors support that kinesin-1 contributes to the anterograde transport of capsids. These results shed light into the mechanisms for anterograde transport of H129-derived tracer in axons and transmission between neurons via synapses, explaining the anterograde labeling of neural circuits by H129-derived tracers.

Published
2020

17. Immune modulation of Th1/Th2/Treg/Th17/Th9/Th21 cells in rabbits infected with Eimeria stiedai

Author

Xiao-Di Chen, Jing Xie, Yong Wei, Ji-Feng Yu, Ye Cao, Lu Xiao, Xue-Jing Wu, Cong-Jian Mao, Run-Min Kang, and Yong-Gang Ye

Subjects
E. stiedai, TBX2, GATA3, RORC, Foxp3, SPI1, Microbiology, QR1-502
Abstract

IntroductionDespite long-term integrated control programs for Eimeria stiedai infection in China, hepatic coccidiosis in rabbits persists. Th1, Th2, Th17, Treg, Th9, and Th21 cells are involved in immune responses during pathogen infection. It is unclear whether Th cell subsets are also involved in E. stiedai infection. Their roles in the immunopathology of this infection remain unknown. Therefore, monitoring these T-cell subsets’ immune responses during primary infection of E. stiedai at both transcriptional (mRNA) and protein (cytokines) levels is essential.MethodsIn experimentally infected New Zealand white rabbits, mRNA expression levels of their transcript—TBX2 (Th1), GATA3 (Th2), RORC (Th17), Foxp3 (Treg), SPI1 (Th9), and BCL6 (Th21)—were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), whereas Th1 (IFN-g and TNF-a), Th2 (IL4), Th17 (IL17A and IL6), Treg (IL10 and TGF-b1), Th9 (IL9), and Th21 (IL21) cytokines were measured using enzyme-linked immunosorbent assays (ELISAs).ResultsWe found that levels of TBX2, GATA3, RORC, SPI1, and BCL6 in the livers of infected rabbits were elevated on days 5 and 15 post-infection (PI). The concentrations of their distinctive cytokines IFN-g and TNF-a for Th1, IL4 for Th2, IL17A for Th17, IL9 for Th9, IL21 for Th21, and IL10 for Treg IL10 were also significantly increased on days 5 and 15 PI, respectively (p < 0.05). On day 23 PI, GATA3 with its cytokine IL4, RORC with IL17A, Foxp3 with IL10 and TGF-b1, and SPI1 with IL9 were significantly decreased, but TBX2 with IFN-g and IL6 remained elevated.DiscussionOur findings are the first evidence of Th1/Th2/Treg/Th17/Th9/Th21 changes in E. stiedai-infected rabbits and provide insights into immune regulation mechanisms and possible vaccine development.

Published
2023
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18. Liquiritin ameliorates metabolic and endocrine alterations in a mouse model of polycystic ovary syndrome

Author

Zhi Li, Yan Liu, Hai-Ou Liu, Zhi-Yong Wu, Cong-Jian Xu, Fei-Fei Zhang, and Yong-Qing Zhu

Subjects
Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Abstract. Objective:. Altered bile acid transformation induces low-grade chronic inflammation and may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). Liquiritincan regulate bile acid metabolism and anti-inflammatory properties; however, limited information is available regarding its therapeutic potential in PCOS. Methods:. Female C57BL/6 mice were randomly assigned into four groups (n = 6 mice/group): the control, letrozole or dehydroepiandrosterone-induced PCOS groups, PCOS + 20 mg/kg liquiritin group, and control + liquiritin groups. After 21 days of treatment, the mice were euthanized, and the associated metabolism indications were investigated. Ovarian histological examinations were performed, and serum hormone concentration was measured. The expression of key genes involved in steroid hormone synthesis, ovarian follicle development, and ovulation was assessed. Results:. Liquiritin reduced fasting blood glucose levels and increased insulin sensitivity compared to the PCOS group. Liquiritin also significantly decreased serum levels of total testosterone (P

Published
2022
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19. The evolution of morphological development is congruent with the species phylogeny in the genus Streptomyces

Author

Min Wang, Cong-Jian Li, Zhen Zhang, Pan-Pan Li, Ling-Ling Yang, and Xiao-Yang Zhi

Subjects
Streptomyces, morphological development, comparative phylogenetics, phylogenetic conflict, Robinson-Foulds distance, Microbiology, QR1-502
Abstract

As the canonical model organism to dissect bacterial morphological development, Streptomyces species has attracted much attention from the microbiological society. However, the evolution of development-related genes in Streptomyces remains elusive. Here, we evaluated the distribution of development-related genes, thus indicating that the majority of these genes were ubiquitous in Streptomyces genomes. Furthermore, the phylogenetic topologies of related strict orthologous genes were compared to the species tree of Streptomyces from both concatenation and single-gene tree analyses. Meanwhile, the reconciled gene tree and normalization based on the number of parsimony-informative sites were also employed to reduce the impact of phylogenetic conflicts, which was induced by uncertainty in single-gene tree inference based merely on the sequence and the bias in the amount of phylogenetic information caused by variable numbers of parsimony-informative sites. We found that the development-related genes had higher congruence to the species tree than other strict orthologous genes. Considering that the development-related genes could also be tracked back to the common ancestor of Streptomyces, these results suggest that morphological development follows the same pattern as species divergence.

Published
2023
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20. How fertility preservation guidelines have progressed worldwide: Potential implications and inspiration

Author

Min-Xin Chen, Ying Zhang, Qing-Qing Cai, Shuo Zhang, Ran Xu, Hua Chen, Yu Kang, Yue Wu, Ri-Cheng Chian, Cong-Jian Xu, and Yong-Qing Zhu

Subjects
Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Abstract. To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women's and Children's Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.

Published
2022
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21. Reshaping force for deformed casing repairing with hydraulic rolling reshaper and its influencing factors.

Author

Hong-Fei Li, Min Luo, Ting-Ting Xu, Qiao-Zhen Li, and Cong-Jian Huang

Subjects
PEARSON correlation (Statistics), FINITE element method, MATHEMATICAL models, STATISTICAL correlation, PROBLEM solving
Abstract

Hydraulic rolling reshaper is an advanced reshaping tool to solve the problem of casing deformation, which has been widely used in recent years. When it is used for well repair operation, the reshaping force provided by ground devices is generally determined by experience. However, too large reshaping force may destroy the deformed casing, and too small reshaping force may also prolong the construction period and affect the repairing effect. In this paper, based on Hertz contact theory and elastic-plastic theory, combined with the process parameters of shaping, and considering the structural characteristics of the deformed casing and reshaper, we propose a mathematical model for calculating the reshaping force required for repairing deformed casing by hydraulic rolling reshaper. Meanwhile, the finite element model and numerical method of hydraulic rolling reshaper repairing deformed casing are established by using the finite element method, and the reliability of the mathematical model is verified by several examples. On this basis, the control variable method is used to investigate the influence of each parameter on the reshaping force, and the influence degree of each parameter is explored by orthogonal simulation test and Pearson correlation analysis. The research results not only provide an important theoretical basis for the prediction of reshaping force in on-site construction, but also provide a reference for the subsequent improvement of the shaping process. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.

Author

Zhang, Kai-Hui, Zhang, Fei-Fei, Zhang, Zhi-Ling, Fang, Ke-Fei, Sun, Wen-Xing, Kong, Na, Wu, Min, Liu, Hai-Ou, Liu, Yan, Li, Zhi, Cai, Qing-Qing, Wang, Yang, Wei, Quan-Wei, Lin, Peng-Cheng, Lin, Yan, Xu, Wei, Xu, Cong-Jian, Yuan, Yi-Yuan, and Zhao, Shi-Min

Abstract

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1 -KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Efficacy and safety of sanjiezhentong capsules, a traditional chinese patent medicine, on long-term management of endometriosis: A randomized controlled trial

Author

Jing-Yao Ruan, Yun-Xi Zheng, Qi Tian, Jun-Ya Ke, Li Wang, Yan Du, Zhi-Ling Zhu, Xiao-Fang Yi, and Cong-Jian Xu

Subjects
alternative medicine, endometriosis, long-term management, sanjiezhentong capsules, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Objective: To compare the efficacy of the traditional Chinese medicine SanJieZhenTong (SJZT) capsules versus gonadotropin-releasing hormone analogs (GnRHa) or oral contraceptives (OCs) in the postoperative treatment of moderate-to-severe endometriosis. Methods: In this prospective clinical trial, women with stage III–IV endometriosis according to the revised American Fertility Society scoring system received three doses of GnRHa immediately after laparoscopic conservative surgery, followed by random assignment to receive treatment with SJZT, GnRHa, or OCs for another 6 months. The primary endpoint was 2-year recurrence, and the secondary endpoints were adverse events, changes in physical function, and quality of life (QoL). Recurrence was assessed using Kaplan–Meier curves and log-rank tests. Generalized estimating equations were used to determine the parameters of the secondary endpoints. Results: A total of 66 women were randomly assigned to the SJZT (n = 21), GnRHa (n = 21), and OCs (n = 24) groups. At a median follow-up of 22 months, no difference in recurrence was found (P = 0.72), with one (4.8%), two (9.5%), and one (4.2%) incidence in the SJZT, GnRHa, and OCs groups, respectively. Expectedly, the incidence of side effects such as hot flush, insomnia, and arthralgia in the SJZT and OCs groups was significantly lower than that in the GnRHa group (P = 0.00). In addition, the female sexual function index was significantly improved in the SJZT group, with a higher value than that in the GnRHa (odds ratio [OR] = 5.25, 95% confidence interval [CI]: 2.09–13.14, P = 0.00) and OCs (OR = 3.94, 95% CI: 1.58–9.83, P = 0.00) groups. Conclusions: SJZT showed more effective pain relief and QoL improvement in patients with moderate-to-severe endometriosis than GnRHa or OCs did. Fewer adverse events than those observed with other agents indicate that this alternative medicine, SJZT, could be a novel option for the long-term management of endometriosis.

Published
2021
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24. A defective CXCL16/CXCR6 axis increases the risk of pregnancy loss via the abnormal crosstalk between decidual γδ t cells and trophoblasts

Author

Deng-Xuan Fan, Ming-Qing Li, Wen-Jie Zhou, Hong-Lan Huang, Hui-Li Yang, and Cong-Jian Xu

Subjects
cxcl16, cxcr6, decidual γδ t cells, maternal–fetal interface, recurrent spontaneous abortion, trophoblasts, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Objective: The maternal–fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus. The interaction between decidual γδ Τ cells and trophoblasts plays a pivotal role during successful pregnancy; however, their physiological functions in early-term human pregnancy are still not completely illustrated. This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidual γδ T cells and HTR8/SVneo trophoblast cells. Methods: The percentile of CXCR6+ γδ T cells in the peripheral blood from normal female and recurrent spontaneous abortion (RSA) patients was analyzed by flow cytometry. The expression of CXCR6 was detected in decidual immune cells via flow cytometry, and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus (LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells. Expression of granzyme B and cytokines and proliferation of decidual γδ T cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry. Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay. Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss. Results: The percentile of CXCR6+ γδ T cells in the peripheral blood from RSA patients was lower than normal pregnancies. The expression of CXCR6 was highest in the decidual γδ T cells among decidual immune cells, and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased. Expression of granzyme B in the decidual γδ T cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16, and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidual γδ T cells. Both the expression of CXCR6 in the decidual γδ T cells and proliferation of the decidual γδ T cells were promoted by HTR8/SVneo trophoblast cells. On the other hand, decidual γδ T cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation. In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidual γδ Τ cells and trophoblasts. Conclusions: Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidual γδ Τ cells and trophoblasts, and it showed a light on the effective strategy of adoptive transfer of CXCR6+ γδ T cells on the treatment of RSA. This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.

Published
2021
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25. Insights into stem cell therapy for premature ovarian insufficiency

Author

Zhen-Le Pei, Zhe-Yi Wang, Wen-Han Lu, Fei-Fei Zhang, Xin Li, Xiao-Yu Tong, Yi Feng, and Cong-Jian Xu

Subjects
premature ovarian failure, premature ovarian insufficiency, regenerative medicine, stem cell, tissue engineering, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Hormone therapy, assisted reproductive technology, and regenerative medicine have been used to treat infertility due to premature ovarian insufficiency (POI), with limited success. It is timely to survey the field by outlining the controversies and promising prospects of evolving stem cell (SC) therapy for patients with POI. We first discuss several strategies of tissue-derived SC therapy and induced/engineered SC therapy and then enumerate mechanisms, including cellular regenerability induced in reproductive tissues and paracrine effects induced by various chemokines. Next, we evaluate the potential benefits of SC-based tissue engineering in reversing ovarian aging. Finally, we discuss the clinical feasibility of SC therapy and generalized regenerative medicine for the treatment of POI. In summary, SCs and SC-derived exosomes, induced pluripotent SCs, engineered SCs, and tissue engineering could start a new chapter for fertility rehabilitation in patients with POI. Uncovering the underlying molecular mechanisms and biological efficacy could be facilitated not only by animal experiments but also by security screening and clinical trials to validate SC-based therapy for POI.

Published
2021
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26. NaturalSpeech: End-to-End Text-to-Speech Synthesis with Human-Level Quality

Author

Tan, Xu, primary, Chen, Jiawei, additional, Liu, Haohe, additional, Cong, Jian, additional, Zhang, Chen, additional, Liu, Yanqing, additional, Wang, Xi, additional, Leng, Yichong, additional, Yi, Yuanhao, additional, He, Lei, additional, Zhao, Sheng, additional, Qin, Tao, additional, Soong, Frank, additional, and Liu, Tie-Yan, additional

Published
2024
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27. Current status and recent advances in preimplantation genetic testing for structural rearrangements

Author

Shuo Zhang, Cai-Xia Lei, Xiao-Xi Sun, and Cong-Jian Xu

Subjects
chromosome aneuploidy, inversion karyotype, preimplantation genetic testing, structural chromosomal rearrangement, structural rearrangement, translocation karyotype, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Preimplantation genetic testing (PGT) is an early form of prenatal genetic diagnosis, which can identify the abnormal embryos cultured in vitro, allow only transfer of genetically normal embryos, and improve the pregnancy rate. In recent years, the rapid development of microarrays and next-generation sequencing (NGS) technologies has remarkably accelerated the clinical application of PGT. In particular, a variety of detection methods have emerged and achieved significant progress in PGT for structural rearrangements (PGT-SR). The detection-related abilities of these methods range from the detection of limited chromosome aneuploidy to comprehensive chromosome screening of the whole genome to differentiation of embryos with normal or balanced translocation/inversion karyotypes. In this study, we reviewed PGT-SR-related detection techniques to provide a better reference for clinical application and research. We have also discussed the potential development of novel techniques in the future.

Published
2020
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28. Diagnostic guidelines for infertility

Author

Zi-Jiang Chen, Jia-Yin Liu, He-Feng Huang, Jie Qiao, Can-Quan Zhou, Guo-Ning Huang, Ying-Pu Sun, Dong-Zi Yang, Xiao-Yan Liang, Qi Yu, Yun Sun, Zheng Li, Li-Qing Fan, Cong-Jian Xu, Yuan-Hua Huang, Xue-Hong Zhang, Jing Yang, Shao-Ming Lu, Lin-Lin Cui, Jun-Hao Yan, and Jin-Fang Lin

Subjects
diagnostic guidelines, etiological classification, infertility evaluation, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Infertility seriously endangers the reproductive health of women at childbearing age. It is defined as the failure to achieve successful pregnancy after 1 year or more of regular unprotected intercourse. Broadly defined, infertility includes two aspects – failure to conceive or have a live birth. This guideline only addressed content relevant to the former. It was proposed by the gynecological endocrine group of the Chinese Society of Obstetrics and Gynecology, Chinese Medical Association, based on relevant guidelines of the World Health Organization, the American Society for Reproductive Medicine, the National Institute for Health and Clinical Excellence, as well as the clinical practice in China. The guideline was reviewed by experts and doctors from medical institutions at all levels, which is applicable to the diagnosis of infertility by physicians in obstetrics, gynecology, and andrology at various medical institutions nationwide.

Published
2020
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29. Global warming and world soybean yields

Author

CAI CHENG-ZHI, LIAO CONG-JIAN, XIAO DAN, ZENG XIAO-SHAN, and ZUO JIN

Subjects
World soybean, yield potential, ARIMA model, global warming, Agriculture
Abstract

The crop yield potential of world soybean from 2019 to 2028 has been projected using ARIMA model based on the yields from 1961 to 2018. Both annual global mean temperature and the yields of world soybean have been projected to rise during the ensuing decade 2019-2028. Projected average yields of world soybean varies from 2841 to 3276 kg ha-1 while 4324 to 4807 kg ha-1 in the case of top (national) yields of world soybean. Annual global mean temperatures may vary from 15.0 to 15.3oC and likely to exert positive impact on average yield (R squared = 0.80) while negative on top yield (R squared = 0.40) of world soybean. It may be concluded that for world soybean yields in 2019 to 2028, the opportunities for improving production should be dependent on both high and low-yielding countries as the yield remained between 30 and 70 per cent of potential limit i.e. in middle place around the turn-point of S-shaped curve in long-term trend partly affected by global warming.

Published
2021
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30. Spectrum of diseases in female children and adolescents admitted to the obstetrics and gynecology hospital, Shanghai, between 2003 and 2017

Author

Hai-Xia Huang, Ming-Xing Zhang, Hong-Wei Zhang, Meng Zhang, Yi Yu, Yu Kang, Gui-Ling Li, and Cong-Jian Xu

Subjects
Children and Adolescents, Disease Attributes, Hospitalized, Reproductive Health Education, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Objective: To investigate the spectrum of diseases in female children and adolescents hospitalized for obstetric and gynecological conditions. Methods: This retrospective study included patients (age ≤19 years) admitted to the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, between January 2003 and December 2017. Their medical records – age, principal diagnosis, and treatment – were reviewed and analyzed. Diagnoses were divided into eight disease classifications. Comparison between groups was analyzed with Student's t-test. Results: This study enrolled 4,628 inpatients. The number of inpatients increased each year, especially in the groups of gynecologic tumors, pregnancy-related conditions, and disorders of the breast. The mean age was 16.33 ± 2.42 years (range: 2–19 years). Of all the inpatients, 41.9% (n = 1,939) were hospitalized for gynecologic tumors, and 85.5% (n = 1,657) of the tumors were benign. Altogether, ovarian cysts (28.66%, n = 1,325) were the most common disease observed in this group. In addition, 32.9% (n = 1,524) of the inpatients were hospitalized for pregnancy, childbirth, and puerperium; within this group, 21.9% (n = 1,014) were hospitalized for artificial abortions. Conclusions: The efforts of all stakeholders toward the implementation of government policies to promote sexual and reproductive health among children and adolescents in China have been effective.

Published
2019
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31. Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats

Author

Yi-Ming Ren, Chuan-Huang Weng, Cong-Jian Zhao, and Zheng-Qin Yin

Subjects
765, retinal degeneration, ganglion cell, intrinsic excitability, patch clamp, Ophthalmology, RE1-994
Abstract

AIM: To evaluate the intrinsic excitability of retinal ganglion cells (RGCs) in degenerated retinas. METHODS: The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS) rats, a common retinitis pigmentosa (RP) model, in a relatively late stage of retinal degeneration (P90) were investigated. Several parameters of RGC morphologies and action potentials (APs) were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. RESULTS: Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells), and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. CONCLUSION: RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies.

Published
2018
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32. Baicalein Ameliorates Chronic Stress-Mediated Ovarian Dysfunction by Upregulating the Expression of Gamma-Aminobutyric Acid B2 Receptor

Author

Ke Li, Jing Li, Jing Xu, Ling Zhang, Qi-Yu Liu, Yun-Ke Huang, Zhi-Gang Zhang, Yu Kang, and Cong-Jian Xu

Subjects
Baicalein, Chronic Stress, Gamma-Aminobutyric Acid B2 Receptor, Ovarian Dysfunction, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background: The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model. Methods: Forty female C57BL/6 mice were randomly divided into four groups as follows: the normal saline group (control, n = 10), the daily stress group (daily stress, n = 10), the baicalein group (baicalein, n = 10), and the daily stress + baicalein group (daily stress + baicalein, n = 10). For the daily stress model, we used a restricted stress model. Baicalein (10 mg/kg) was administered by gavage every day, and control mice received normal saline equivalently. Biopsy specimens were harvested after 4 weeks. Measurement of norepinephrine (NE) in serum was performed to assess the psychological stress level of the mice. In addition, histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone (AMH) in serum were assessed to evaluate changes in ovarian function. To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction, immunohistochemical methods, and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid (GABA) receptors. Results: Compared with values in the control group, serum NE concentrations were significantly increased (P < 0.001), AMH concentrations were markedly decreased (P < 0.01), the thickness of the endometrium was clearly reduced, and the percentage of atretic follicles was significantly increased in the daily stress group (P < 0.001), indicating that the chronic stress model was successfully established. In contrast, compared with values in the daily stress group, serum NE concentrations were significantly reduced (P < 0.001), AMH concentrations were significantly enhanced (P < 0.05), the thickness of the endometrium was clearly increased, and the percentage of atretic follicles was significantly reduced (P < 0.001) in the daily stress + baicalein group, indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress. Moreover, the expression of the GABAB2receptor in the daily stress group was significantly reduced (P < 0.01). In contrast, treatment with baicalein resulted in increased expression of the GABAB2receptor (P < 0.01). Conclusions: Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction, and the mechanism can be attributed, in part, to the increased expression of the GABAB2receptor.

Published
2018
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33. Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer

Author

Shan-Shan Hong, Ming-Xing Zhang, Meng Zhang, Yi Yu, Jun Chen, Xiao-Yan Zhang, and Cong-Jian Xu

Subjects
ovarian carcinoma, targeted therapy, follicle-stimulating hormone, growth-regulated oncogene α, short hairpin rna, Therapeutics. Pharmacology, RM1-950
Abstract

The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer.

Published
2018
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34. Transcriptional control of the MUC16 promoter facilitates follicle-stimulating hormone peptide-conjugated shRNA nanoparticle-mediated inhibition of ovarian carcinoma in vivo

Author

Ming-Xing Zhang, Shan-Shan Hong, Qing-Qing Cai, Meng Zhang, Jun Chen, Xiao-Yan Zhang, and Cong-Jian Xu

Subjects
ovarian carcinoma, muc16, follicle-stimulating hormone, targeted therapy, nanoparticle, Therapeutics. Pharmacology, RM1-950
Abstract

Ovarian cancer is the leading cause of cancer death among gynecological malignancies. The high mortality rate has not been significantly reduced despite advances in surgery and chemotherapy. Gene therapy shows therapeutic potential, but several key issues must be resolved before clinical application. To minimize toxicity in noncancerous tissues, tumor-specific ligands are conjugated to vectors to increase the selectivity of drug delivery. The expression pattern of follicle-stimulating hormone (FSH) receptor in normal and cancer tissues provides an opportunity for highly selective drug delivery in ovarian cancer. Furthermore, tumor-specific promoters can conditionally regulate therapeutic gene expression in tumor or normal tissues. The mucin 16 (MUC16) promoter might be a potential tool to drive ovarian cancer-localized gene expression since MUC16/CA125 is overexpressed in most ovarian carcinomas. Here, we screened the possible MUC16 promoter sequences and constructed MUC16 promoter-driven gro-α shRNA plasmid vectors. The vectors were specifically delivered into ovarian cancer cells via FSH peptide-conjugated nanoparticles. The predicted promoter sequence with TAAA repeats showed high transcriptional activity. The nanoparticle complex containing MUC16 promoter-driven gro-α shRNA and FSH peptides had the ability to decrease gro-α protein secretion in ovarian cancer cells and block tumor growth without obvious toxic effects in a nude mouse model bearing ovarian cancer. Our study provides a novel gene delivery system using a MUC16 promoter trigger and FSH peptide-mediated active targeting in ovarian cancer, and this system may be a promising strategy for specific genetic therapeutic delivery.

Published
2018
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38. Proteomic profiling of early degenerative retina of RCS rats

Author

Zhi-Hong Zhu, Yan Fu, Chuan-Huang Weng, Cong-Jian Zhao, and Zheng-Qin Yin

Subjects
889, retinal degeneration, proteomics, mitochondrion, E2F1, MaxQuant, RCS rat, Ophthalmology, RE1-994
Abstract

AIM: To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). METHODS: Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. RESULTS: In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student’s t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. CONCLUSION: We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

Published
2017
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39. Roles of Meiotic Defects in Pathogenesis of Primary Ovarian Insufficiency

Author

Ling Zhang, Qi-Qi Wang, Cheng-Qiu Tao, and Cong-Jian Xu

Subjects
Genetic Factors, Genotype–Phenotype Correlation, Meiosis, Ovarian Reserve, Primary Ovarian Insufficiency, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

A matured oocyte has experienced three critical division stages: (1) proliferation in early fetal stage, (2) meiotic arrest at diplotene of prophase I, and (3) meiotic resumption and extrusion of the first polar body. The abnormalities of these stages are associated closely with female reproduction problems including primary ovarian insufficiency (POI), the pathogenic mechanisms of which consist of insufficient initial follicle number, accelerated follicle loss, and arrest of follicle development. Recently, many meiotic associated genetic factors were identified to be mutated in POI patients and mouse models, revealing the association between meiosis and ovarian reserve. In this review, we provide an overview of the genetic factors involved in meiotic prophase I and their pathogenic mechanisms in POI.

Published
2017
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40. Dysbiosis of gut microbiota contributes to chronic stress in endometriosis patients via activating inflammatory pathway

Author

Jing Xu, Ke Li, Lin Zhang, Qi-Yu Liu, Yun-Ke Huang, Yu Kang, and Cong-Jian Xu

Subjects
Chronic Stress, Endometriosis, Gut Microbiota, Gut-brain Axis, Immunologic diseases. Allergy, RC581-607, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background: Gut microbiota can interact with the central nervous system through the gut–brain axis, thus affecting the host's chronic stress level, such as anxiety and depression. Current researches show that patients with endometriosis often have a high level of chronic stress, which will in turn aggravate endometriosis by activating the β-adrenergic signaling pathway. Therefore, we wondered whether the gut microbiota associates with the chronic stress level in endometriosis patients, which may provide new insights on how to improve treatment. Methods: We grouped the endometriosis patients into the chronic stress group and the control group with questionnaires such as generalized anxiety disorder-7 and patient health questionnaire-9 and collected patients' fecal specimens and tissue specimens. Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method, and immunohistochemistry was performed to detect the activation of inflammatory pathways in endometriosis tissues. Results: We found that in patients with endometriosis, the dysbiosis of gut microbiota was associated with their stress levels. Furthermore, the levels of Paraprevotella, Odoribacter, Veillonella, and Ruminococcus were significantly reduced in chronic stressed endometriosis patients, suggestive of a disease-specific change of gut microbiota at the genus level. Compared to the healthy women, the expression levels of inflammatory cytokines, nuclear factor-κB p65, and cyclooxygenase-2 increased in the chronic stressed endometriosis patients, indicating that the dysbiosis of gut microbiota may activate the inflammatory pathway of gut–brain axis. Conclusions: We hypothesized that these new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis may be a new examination target of chronic stress level. These changes may also provide new insights for psychological intervention, thus reducing the stress level and improving the prognosis of endometriosis patients.

Published
2017
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41. Detection of circulating tumor cells and evaluation of epithelial-mesenchymal transition patterns of circulating tumor cells in ovarian cancer

Author

Xiao-Xiang, Jie, Meng, Zhang, Ming, Du, Qing-Qing, Cai, Qing, Cong, Cong-Jian, Xu, and Xiao-Yan, Zhang

Subjects
Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging
Abstract

Circulating tumor cells (CTCs) have considered to be promising liquid biopsy in cancer due to the intact information of whole cells and the potential to reflect micrometastasis. However, CTCs research are extremely limited in ovarian cancer, probably due to their rarity. The predictive value of CTCs and circulating tumor microemboli (CTM) in metastasis remains to be elucidated in ovarian cancer. This study tried to identify CTCs/CTM in ovarian cancer with considerably positive rate. To preliminarily identify the invasive capacity of CTCs/CTM, the epithelial-mesenchymal transition (EMT) patterns of CTCs/CTM was evaluated. Moreover, for comprehensive understanding of invasiveness of disseminated cells in ovarian cancer, EMT pattern of exfoliated tumor cells in ascites were also confirmed in this study.Peripheral blood samples and ascites samples were collected from 22 ovarian cancer patients. The Microfiltration combined with morphological analysis was used to detect CTC single cells or cell clusters. Microfiltration combined with morphological analysis was applied in the CTC isolation and identification. EMT was evaluated by immunofluorescence via markers including vimentin and cytokeratin.Microfiltration combined with morphological analysis was introduced to detect CTCs/CTM with a positivity rate of 40.9% in ovarian cancer patients. The number of CTC varied from 1 to 8, with CTM number from 4 to 30. CTCs/CTM of all samples have experienced EMT process. Vimentin was expressed in all CTC samples and all tumor cells in ascites, while cytokeratin was expressed in 44.4% (4/9) of CTC samples. There were no significant differences of the clinical parameters between the CTC-positive and CTC-negative patients.This study showed that both CTCs/CTM and detached tumor cells in ascites might have undergone complete or partial EMT in ovarian cancer. Moreover, microfiltration combined with cytomorphological analysis showed a considerable CTC detection rate.

Published
2022

42. Preimplantation genetic testing guidelines of International Society of Reproductive Genetics

Author

Chen-Ming Xu, Si-Jia Lu, Song-Chang Chen, Jing-Lan Zhang, Cong-Jian Xu, Yuan Gao, Yi-Ping Shen, Yun-Xia Cao, Ling-Qian Wu, Fan Jin, Ge Lin, Ping Liu, Yi-Min Zhu, Yan-Ting Wu, Dan Zhang, Bill Yee, Vitaly A. Kushnir, Zhi-Hong Yang, Jia-Yin Liu, Zi-Jiang Chen, Alan Thornhill, Angie N. Beltsos, Johan Smitz, John Frattarelli, Alan Handyside, Jie Qiao, and He-Feng Huang

Subjects
Reproductive Medicine, Obstetrics and Gynecology
Published
2022

50. BMP4 Cross-talks With Estrogen/ERα Signaling to Regulate Adiposity and Glucose Metabolism in Females

Author

Shu-wen Qian, Yan Liu, Jue Wang, Ji-Chan Nie, Meng-yuan Wu, Yan Tang, Ya-Xin Zhao, Xi Li, Hai-yan Huang, Liang Guo, Xi-shi Liu, Cong-jian Xu, and Qi-qun Tang

Subjects
BMP4, Estrogen, ERα, White adipose tissue, Glucose metabolism, Medicine, Medicine (General), R5-920
Abstract

Similar to estrogens, bone morphogenetic protein 4 (BMP4) promotes the accumulation of more metabolically active subcutaneous fat and reduction of visceral fat. However, whether there is a cross-talk between BMP4 and estrogen signaling remained unknown. Herein, we found that BMP4 deficiency in white adipose tissue (WAT) increased the estrogen receptor α (ERα) level and its signaling, which prevented adult female mice from developing high fat diet (HFD)-induced obesity and insulin resistance; estrogens depletion up regulated BMP4 expression to overcome overt adiposity and impaired insulin sensitivity with aging, and failure of BMP4 regulation due to genetic knockout led to more fat gain in aged female mice. This mutual regulation between BMP4 and estrogen/ERα signaling may also happen in adipose tissue of women, since the BMP4 level significantly increased after menopause, and was inversely correlated with body mass index (BMI). These findings suggest a counterbalance between BMP4 and estrogen/ERα signaling in the regulation of adiposity and relative metabolism in females.

Published
2016
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