NON-SYNDROMIC HEARING LOSS AND HIGH- THROUGHPUT STRATEGIES TO DECIPHER ITS GENETIC HETEROGENEITY

Hearing loss (HL) is the most common sensory disorder, affecting all age groups, ethnicities, and gen-ders. According to World Health Organization (WHO) estimates in 2005, 278 million people worldwide have moderate to profound HL in both ears. Results of the 2002 National Health Interview Survey indicate that nearly 31 million of all non-institutionalized adults (aged 18 and over) in the United States have trouble hearing. Epidemiological studies have estimated that approximately 50%of profound HL can be attributed to genetic causes. With over 60 genes implicated in nonsyndromic hearing loss, it is also an extremely het-erogeneous trait. Recent progress in identifying genes responsible for hearing loss enables otolaryngologists and other clinicians to apply molecular diagnosis by genetic testing. The advent of the $1000 genome has the potential to revolutionize the identification of genes and their mutations underlying genetic disorders. This is especially true for extremely heterogeneous Mendelian conditions such as deafness, where the muta-tion, and indeed the gene, may be private. The recent technological advances in target-enrichment methods and next generation sequencing offer a unique opportunity to break through the barriers of limitations im-posed by gene arrays. These approaches now allow for the complete analysis of all known deafness-causing genes and will result in a new wave of discoveries of the remaining genes for Mendelian disorders. This re-view focuses on describing genotype-phenotype correlations of the most frequent genes including GJB2, which is responsible for more than half of cases, followed by other common genes and on discussing the im-pact of genomic advances for comprehensive genetic testing and gene discovery in hereditary hearing loss.

A New Definition of Modularity for Community Detection in Complex Networks

We propose a new definition of modularity,i.e.the Qd function,for network analysis,which takes the edge density and topological structure of modules into account and is different from the original strategy of simply calculating the number of edges(the definition of modularity Q introduced by Newman and Girvan).Armed with this novel quality function Qd,we implement an adaptive clustering algorithm for process optimization,and apply our strategy to several synthetic and real-world networks.The results of our exercises demonstrate a better performance in extracting accurate community ingredients from complex networks.

DETECTION AND APPLICATION OF MICROFLUIDIC ISOTHERMAL AMPLIFICATION ON CHIP

Loop-mediated isothermal amplification(LAMP)is a novel nucleic acid amplification method.Compared with the widely utilized polymerase chain reaction(PCR),LAMP has higher speed and efficiency as well as lower requirement for system temperature control because the whole amplification process is isothermal and no efforts are needed to switch between different temperatures.In this paper,we designed and fabricated different kinds of polycarbonate(PC)microfluid chips,explored appropriate reaction condition for LAMP in microenvironment(1 nL→10μL),and developed a microfluidic isothermal amplification detection system.The DNA optimal amplification temperature is obtained;the starting time of exponential amplification of DNA is put forward farther.The optimal condition of DNA amplification in microenvironment,with a little reaction materials and early starting exponential amplification time of DNA are very important for clinic DNA detection and the application of Lab-on-a-Chip.

LABEL-FREE DETECTION OF PROTEIN MICROARRAY WITH HIGH THROUGHPUT SURFACE PLASMON RESONANCE IMAGING(SPRI)

A surface plasmon resonance imaging(SPRI)system was developed for the discrimination of proteins on a gold surface.As a label-free and high-throughput technique,SPRI enables simultaneously monitoring of the biomolecular interactions at low concentrations.We used SPRI as a label-free and parallel method to detect different proteins based on protein microarray.Bovine Serum Albumin(BSA),Casein and Immunoglobulin G(IgG)were immobilized onto the Au surface of a gold-coated glass chip as spots forming a 6×6 matrix.These proteins can be discriminated directly by changing the incident angle of light.Excellent reproducibility for label-free detection of protein molecules was achieved.This SPRI platform represents a simple and robust method for performing high-sensitivity detection of protein microarray.

Deep Learning and Its Applications in Biomedicine

Advances in biological and medical technologies have been providing us explosive vol- umes of biological and physiological data, such as medical images, electroencephalography, geno- mic and protein sequences. Learning from these data facilitates the understanding of human health and disease. Developed from artificial neural networks, deep learning-based algorithms show great promise in extracting features and learning patterns from complex data. The aim of this paper is to provide an overview of deep learning techniques and some of the state-of-the-art applications in the biomedical field. We first introduce the development of artificial neural network and deep learning. We then describe two main components of deep learning, i.e., deep learning architectures and model optimization. Subsequently, some examples are demonstrated for deep learning

Gene expression signatures for phlegm-dampness constitution of Chinese Medicine

Dear Editor, The term ＂individualized medicine＂ was first used in Bio- chemistry Individuality in 1956 by Williams （Williams et al., 1956）. With the emergence of the post-genome era in the 21 st century, individualized precision medicine has attracted increasing attention. In traditional Chinese medicine （TCM）, there is also concept of individualized medicine, which is known as the Chinese constitutional theory, proposed in the 1970s （Wang, 2012）. According to this theory, the human population is divided into nine constitutions, including one balanced constitution （Normality） and eight unbalanced constitutions （Yang-deficient, Yin-deficient, Qi-deficient,

Dendrocalamus latiflorus and its component rutin exhibit glucose-lowering activities by inhibiting hepatic glucose production via AKT activation

The potential medicinal value of Ma bamboo(Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract(DLE) reduced fasting blood glucose levels, body weight,and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways.Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase(G6 PC) and phosphoenolpyruvate carboxykinase 1(PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor(IGF1 R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

A large-scale transcriptional study reveals inhibition of COVID-19 related cytokine storm by traditional Chinese medicines

The application of traditional Chinese medicine(TCM)has made great contributions to the fight against the epidemic of coronavirus disease-2019(COVID-19).Despite the remarkable therapeutic effects of TCM,the molecular mechanisms of TCM formulae inhibiting COVID-19 are still not fully understood.Here,we cφm-bined the automated high throughput sequencing-based high throughput screening(HTS^(2))assay with bioinformatics and computer-aided drug design(CADD)to investigate the molecular mechanisms of TCM-mediated therapeutic effects on COVID-19-related cytokine storm(Fig.1a).

Evaluation of the immunomodulatory effects of anti-COVID-19 TCM formulae by multiple virus-related pathways

Dear Editor,The coronavirus infectious disease 2019(COVID-19)outbreak is seriously endangering human health.Most patients with severe COVID-19 are characterized by sustained cytokine production and hyper-inflammation,which is known as cytokine storm syndrome.1-3 Elaborating the anti-inflammatory response is crucial to these patients,and interieukin-6(IL6)inhibitors and steroids have been recommended in clinical practice.1 However,after the cytokine storm phase,the host immune response to sepsis may develop into a protracted immunosuppressive phase.

A transcriptome-based analysis reveals functional differences among Dendrobium officinale Kimura&Migo species from different growing regions and with different quality levels

Dendrobium officinale Kimura&Migo(D.officinale)is a common,high medicinal value food and herbal medicine used in the treatment of yin-deficient diseases.Adulterants obtained with similar inexpensive species of Dendrobium plants are available in the market.However,Dendrobium species with different quality levels or from different regions as well as analogous species have a similar appearance,which makes the discrimination of Dendrobium species difficult.Reliable objective methods for authenticating D.officinale are lacking.Here,samples of Dendrobium officinale Kimura&Migo(D.officinale)from two regions with three quality levels and sample of the analogous species Dendrobium compactum Rolfe ex W.Hackett(D.compactum)were subjected to genome-wide biological response fingerprinting(BioReF)in RAW264.7 cells by RNA sequencing.The biological pathways affected by these samples could distinguish D.officinale from D.compactum.The high-quality D.officinale samples from Yunnan exhibited the strongest inhibition of lipopolysaccharide(LPS)induced inflammatory genes and pathways,followed by samples from Myanmar.The medium-and low-quality samples from Yunnan exhibited weaker effects,and D.compactum exerted mild effects.The RNA sequencing results were strengthened by the results from analyses of the expression of the inflammation-related genes Il6,Ccl5,and Cox2 and the production of nitric oxide.Thus,transcriptomic profiling can be used to evaluate the quality of D.officinale and distinguish its origin.