A Heterozygous Phospholamban Variant(p.R14del)Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy

This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy(ARVC)caused by pathogenic mutations in the Phospholamban(PLN)gene.The study included 170 patients who had a confrmed diagnosis of ARVC and underwent PLN genetic screening using next-generation sequencing.The fndings of this study provide valuable insights into the association between PLN mutations and ARVC,which can aid in the development of more efective diagnostic and treatment strategies for ARVC patients.Out of the patients evaluated,six had a rare pathogenic mutation in PLN with the same p.R14del variant.Family screening revealed that heterozygous carriers of p.R14del exhibited a defnite ARVC phenotype.In clinical studies,individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome mutations.After adjusting for covariates,individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations(95%CI 1.08–6.82,p=0.035).The accumulation of left ventricular fat and fbers is a pathological marker for ARVC patients with p.R14del mutations.In a cohort of 170 Chinese ARVC patients,three point fve percent of probands had the PLN pathogenic variant(p.R14del)and all were female.Our data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure,which requires clinical diferentiation from classic ARVC.Furthermore,carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients.

Allergic Phenotypes and Sarcopenia:Evidence from Observational Studies and Mendelian Randomization Analysis

Commonly afected in early-life population,the impact of allergic phenotypes on mid-or late-life health is less discussed.This study is to explore the association of allergic phenotypes including atopic dermatitis(AD),asthma,eosinophils count(EC),and sarcopenia.We conducted observational studies and mendelian randomization(MR)analysis based on UK Biobank(UKB),the China Health and Retirement Longitudinal Study(CHARLS)and data from genome-wide association study(GWAS).Based on the UKB data,AD,asthma and EC were positively correlated with pre-sarcopenia and decreased skeletal muscle mass index and hand grip in fully adjusted model.Asthma and EC were signifcantly associated with sarcopenia while AD was marginally associated(p=0.095).Based on the CHARLS cohort,asthma signifcantly added 109.4%risk for pre-sarcopenia in adjusted model(relative risk=2.094;p=0.002),respectively.Both asthma(β=0.100,p=0.006)and EC(β=0.023,p=0.017)exerted signifcantly casual efects on pre-sarcopenia.However,as for sarcopenia,merely EC exhibited a signifcantly casual efect(β=0.005,p=0.048).Signifcant casual efects of AD(β=–0.027,p=0.003),asthma(β=–0.029,p=0.027)and EC(β=–0.041,p<0.001)on decreased appendicular lean mass(ALM)were observed using the inverse-variance weighted method and the Mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)method.Our results revealed a contributory role of AD,asthma and EC on sarcopenia,especially in terms of decreased ALM,an indicator for sarcopenia diagnosis.The fndings of our study will raise the awareness of preventing aging-related disorders or geriatric syndromes among allergic populations.

The Protocol of Ultrasonic Backscatter Measurements of Musculoskeletal Properties

This study aims to introduce the protocol for ultrasonic backscatter measurements of musculoskeletal properties based on a novel ultrasonic backscatter bone diagnostic(UBBD)instrument.Dual-energy X-ray absorptiometry(DXA)can be adopted to measure bone mineral density(BMD)in the hip,spine,legs and the whole body.The muscle and fat mass in the legs and the whole body can be also calculated by DXA body composition analysis.Based on the proposed protocol for backscatter measurements by UBBD,ultrasonic backscatter signals can be measured in vivo,deriving three backscatter parameters[apparent integral backscatter(AIB),backscatter signal peak amplitude(BSPA)and the corresponding arrival time(BSPT)].AIB may provide important diagnostic information about bone properties.BSPA and BSPT may be important indicators of muscle and fat properties.The standardized backscatter measurement protocol of the UBBD instrument may have the potential to evaluate musculoskeletal characteristics,providing help for promoting the application of the backscatter technique in the clinical diagnosis of musculoskeletal disorders(MSDs),such as osteoporosis and muscular atrophy.

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline:A Community‑Based Cohort Study

Cardiovascular health metrics are now widely recognized as modifable risk factors for cognitive decline and dementia.Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia.Circulating metabolites profling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline.In a prospective community-based cohort in China(n=725),312 serum metabolic phenotypes were quantifed,and cardiovascular health score was calculated including smoking,exercise,sleep,diet,body mass index,blood pressure,and blood glucose.Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline.A better cardiovascular health was signifcantly associated with lower risk of concentration decline and orientation decline(hazard ratio(HR):0.84–0.90;p<0.05).Apolipoprotein-A1,high-density lipoprotein(HDL)cholesterol,cholesterol ester,and phospholipid concentrations were signifcantly associated with a lower risk of longitudinal memory and orientation decline(p<0.05 and adjusted-p<0.20).Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and-3(proportion of mediation:7.68–8.21%,both p<0.05).Cardiovascular risk factors were associated with greater risks of cognitive decline,which were found to be mediated by circulating lipoproteins,particularly the medium-size HDL components.These fndings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.

Next‑Generation Sequencing‑Based Copy Number Variation Analysis in Chinese Patients with Primary Ciliary Dyskinesia Revealed Novel DNAH5 Copy Number Variations

Primary ciliary dyskinesia(PCD)is a rare disorder characterized by extensive genetic heterogeneity.However,in the genetic pathogenesis of PCD,copy number variation(CNV)has not received sufcient attention and has rarely been reported,especially in China.Next-generation sequencing(NGS)followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing(WES)analysis.Quantitative real-time polymerase chain reaction(qPCR)and Sanger sequencing were used to confrm these CNVs.To further characterize the ciliary phenotypes,high-speed video microscopy analysis(HSVA),transmission electron microscopy(TEM),and immunofuorescence(IF)analysis were used.Patient 1(F1:II-1),a 0.6-year-old girl,came from a nonconsanguineous family-I.She presented with situs inversus totalis,neonatal respiratory distress,and sinusitis.The nasal nitric oxide level was markedly reduced.The respiratory cilia beat with reduced amplitude.TEM revealed shortened outer dynein arms(ODA)of cilia.chr5:13717907-13722661del spanning exons 71–72 was identifed by NGS-based CNV analysis.Patient 2(F2:IV-4),a 37-year-old man,and his eldest brother Patient 3(F2:IV-2)came from a consanguineous family-II.Both had sinusitis,bronchiectasis and situs inversus totalis.The respiratory cilia of Patient 2 and Patient 3 were found to be uniformly immotile,with ODA defects.Two novel homozygous deletions chr5:13720087_13733030delinsGTTTTC and chr5:13649539_13707643del,spanning exons 69–71 and exons 77–79 were identifed by NGS-based CNV analysis.Abnormalities in DNA copy number were confrmed by qPCR amplifcation.IF showed that the respiratory cilia of Patient 1 and Patient 2 were defcient in dynein axonemal heavy chain 5(DNAH5)protein expression.This report identifed three novel DNAH5 disease-associated variants by WES-based CNV analysis.Our study expands the genetic spectrum of PCD with DNAH5 in the Chinese population.

Analysis of the Immune Response by Standardized Whole‑Blood Stimulation with Metabolism Modulation

The immune system defends the body from infection and plays a vital role in a wide range of health conditions.Metabolism afects a series of physiological processes,including those linked to the function of human immune system.Cellular metabolism modulates immune cell activation and cytokine production.Understanding the relationship between metabolism and immune response has important implications for the development of immune-based therapeutics.However,the deployment of large-scale functional assays to investigate the metabolic regulation of immune response has been limited by the lack of standardized procedures.Here,we present a protocol for the analysis of immune response using standardized whole-blood stimulation with metabolism modulation.Diverse immune stimuli including pattern recognition receptor(PRR)ligands and microbial stimuli were incubated with fresh human whole blood.The metabolic inhibitors were used to modulate metabolic status in the immune cells.The variable immune responses after metabolic interventions were evaluated.We described in detail the main steps involved in the whole-blood stimulation and cytokines quantifcation,namely,collection and treatment of whole blood,preparation of samples and controls,cytokines detection,and stimulation with metabolic interventions.The metabolic inhibitors for anabolic pathways and catabolic pathways exert selective efects on the production of cytokines from immune cells.In addition to a robust and accurate assessment of immune response in cohort studies,the standardized whole-blood stimulation with metabolic regulation might provide new insights for modulating immunity.

Investigating the Immunogenic Cell Death‑Dependent Subtypes and Prognostic Signature of Triple‑Negative Breast Cancer

Recently,immunotherapy has emerged as a promising and efective method for treating triple-negative breast cancer(TNBC).However,challenges still persist.Immunogenic cell death(ICD)is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells.Nevertheless,the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood.In this study,we observed dysregulation of the ICD process and verifed the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction(qRT-PCR)analysis.To investigate the potential role of the ICD process in TNBC progression,we determined the ICD-dependent subtypes,and two were identifed.Analysis of their distinct tumor immune microenvironment(TIME)and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune“cold”and“hot”phenotypes,respectively.In addition,we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability.The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identifcation of targeted efective agents for individualized clinical strategies.

De Novo Dissecting the Three‑Dimensional Facial Morphology of 2379 Han Chinese Individuals

Phenotypic diversity,especially that of facial morphology,has not been fully investigated in the Han Chinese,which is the largest ethnic group in the world.In this study,we systematically analyzed a total of 14,838 facial traits representing 15 categories with both a large-scale three-dimensional(3D)manual landmarking database and computer-aided facial segmented phenotyping in 2379 Han Chinese individuals.Our results illustrate that homogeneous and heterogeneous facial morphological traits exist among Han Chinese populations across the three geographical regions:Zhengzhou,Taizhou,and Nanning.We identifed 1560 shared features from extracted phenotypes,which characterized well the basic facial morphology of the Han Chinese.In particular,heterogeneous phenotypes showing population structures corresponded to geographical subpopulations.The greatest facial variation among these geographical populations was the angle of glabella,left subalare,and right cheilion(p=3.4×10^(−161)).Interestingly,we found that Han Chinese populations could be classifed into northern Han,central Han,and southern Han at the phenotypic level,and the facial morphological variation pattern of central Han Chinese was between the typical diferentiation of northern and southern Han Chinese.This result was highly consistent with the results revealed by the genetic data.These fndings provide new insights into the analysis of multidimensional phenotypes as well as a valuable resource for further facial phenotype-genotype association studies in Han Chinese and East Asian populations.

Multimodal Omics Approaches to Aging and Age‑Related Diseases

Aging is associated with a progressive decline in physiological capacities and an increased risk of aging-associated disorders.An increasing body of experimental evidence shows that aging is a complex biological process coordinately regulated by multiple factors at diferent molecular layers.Thus,it is difcult to delineate the overall systematic aging changes based on single-layer data.Instead,multimodal omics approaches,in which data are acquired and analyzed using complementary omics technologies,such as genomics,transcriptomics,and epigenomics,are needed for gaining insights into the precise molecular regulatory mechanisms that trigger aging.In recent years,multimodal omics sequencing technologies that can reveal complex regulatory networks and specifc phenotypic changes have been developed and widely applied to decode aging and age-related diseases.This review summarizes the classifcation and progress of multimodal omics approaches,as well as the rapidly growing number of articles reporting on their application in the feld of aging research,and outlines new developments in the clinical treatment of age-related diseases based on omics technologies.

Phenomic Studies on Diseases:Potential and Challenges

The rapid development of such research field as multi-omics and artificial intelligence(AI)has made it possible to acquire and analyze the multi-dimensional big data of human phenomes.Increasing evidence has indicated that phenomics can pro-vide a revolutionary strategy and approach for discovering new risk factors,diagnostic biomarkers and precision therapies of diseases,which holds profound advantages over conventional approaches for realizing precision medicine:first,the big data of patients'phenomes can provide remarkably richer information than that of the genomes;second,phenomic studies on diseases may expose the correlations among cross-scale and multi-dimensional phenomic parameters as well as the mecha-nisms underlying the correlations;and third,phenomics-based studies are big data-driven studies,which can significantly enhance the possibility and efficiency for generating novel discoveries.However,phenomic studies on human diseases are still in early developmental stage,which are facing multiple major challenges and tasks:first,there is significant deficiency in analytical and modeling approaches for analyzing the multi-dimensional data of human phenomes;second,it is crucial to establish universal standards for acquirement and management of phenomic data of patients;third,new methods and devices for acquirement of phenomic data of patients under clinical settings should be developed;fourth,it is of significance to establish the regulatory and ethical guidelines for phenomic studies on diseases;and fifth,it is important to develop effective international cooperation.It is expected that phenomic studies on diseases would profoundly and comprehensively enhance our capacity in prevention,diagnosis and treatment of diseases.

Phenomic Imaging

Human phenomics is defned as the comprehensive collection of observable phenotypes and characteristics infuenced by a complex interplay among factors at multiple scales.These factors include genes,epigenetics at the microscopic level,organs,microbiome at the mesoscopic level,and diet and environmental exposures at the macroscopic level.“Phenomic imaging”utilizes various imaging techniques to visualize and measure anatomical structures,biological functions,metabolic processes,and biochemical activities across diferent scales,both in vivo and ex vivo.Unlike conventional medical imaging focused on disease diagnosis,phenomic imaging captures both normal and abnormal traits,facilitating detailed correlations between macro-and micro-phenotypes.This approach plays a crucial role in deciphering phenomes.This review provides an overview of diferent phenomic imaging modalities and their applications in human phenomics.Additionally,it explores the associations between phenomic imaging and other omics disciplines,including genomics,transcriptomics,proteomics,immunomics,and metabolomics.By integrating phenomic imaging with other omics data,such as genomics and metabolomics,a comprehensive understanding of biological systems can be achieved.This integration paves the way for the development of new therapeutic approaches and diagnostic tools.

Knowledge Distillation Facilitates the Lightweight and Efficient Plant Diseases Detection Model

Plant disease diagnosis in time can inhibit the spread of the disease and prevent a large-scale drop in production,which benefits food production.Object detection-based plant disease diagnosis methods have attracted widespread attention due to their accuracy in classifying and locating diseases.However,existing methods are still limited to single crop disease diagnosis.More importantly,the existing model has a large number of parameters,which is not conducive to deploying it to agricultural mobile devices.Nonetheless,reducing the number of model parameters tends to cause a decrease in model accuracy.To solve these problems,we propose a plant disease detection method based on knowledge distillation to achieve a lightweight and efficient diagnosis of multiple diseases across multiple crops.In detail,we design 2 strategies to build 4 different lightweight models as student models:the YOLOR-Light-v1,YOLOR-Light-v2,Mobile-YOLOR-v1,and Mobile-YOLOR-v2 models,and adopt the YOLOR model as the teacher model.We develop a multistage knowledge distillation method to improve lightweight model performance,achieving 60.4%mAP@.5 in the PlantDoc dataset with small model parameters,outperforming existing methods.Overall,the multistage knowledge distillation technique can make the model lighter while maintaining high accuracy.Not only that,the technique can be extended to other tasks,such as image classification and image segmentation,to obtain automated plant disease diagnostic models with a wider range of lightweight applicability in smart agriculture.Our code is available at https://github.com/QDH/MSKD.

PDDD-PreTrain:A Series of Commonly Used Pre-Trained Models Support Image-Based Plant Disease Diagnosis

Plant diseases threaten global food security by reducing crop yield;thus,diagnosing plant diseases is critical to agricultural production.Artificial intelligence technologies gradually replace traditional plant disease diagnosis methods due to their time-consuming,costly,inefficient,and subjective disadvantages.As a mainstream AI method,deep learning has substantially improved plant disease detection and diagnosis for precision agriculture.In the meantime,most of the existing plant disease diagnosis methods usually adopt a pre-trained deep learning model to support diagnosing diseased leaves.However,the commonly used pre-trained models are from the computer vision dataset,not the botany dataset,which barely provides the pre-trained models sufficient domain knowledge about plant disease.Furthermore,this pre-trained way makes the final diagnosis model more difficult to distinguish between different plant diseases and lowers the diagnostic precision.To address this issue,we propose a series of commonly used pre-trained models based on plant disease images to promote the performance of disease diagnosis.In addition,we have experimented with the plant disease pre-trained model on plant disease diagnosis tasks such as plant disease identification,plant disease detection,plant disease segmentation,and other subtasks.The extended experiments prove that the plant disease pre-trained model can achieve higher accuracy than the existing pre-trained model with less training time,thereby supporting the better diagnosis of plant diseases.In addition,our pre-trained models will be open-sourced at https://pd.samlab.cn/and Zenodo platform https://doi.org/10.5281/zenodo.7856293.

Infuence of Gender on Tau Precipitation in Alzheimer’s Disease According to ATN Research Framework

Tau proteins accumulation and their spreading pattern were afected by gender in cognitive impairment patients,especially in the progression of Alzheimer’s disease(AD).However,it was unclear whether the gender efects for tau deposition infuenced by amyloid deposition.The aim of this study was to investigate gender diferences for tau depositions in Aβpositive(A^(+))subjects.In this study,tau and amyloid positron emission tomography images,structural magnetic resonance imaging images,and demographic information were collected from 179 subjects in Alzheimer’s Disease Neuroimaging Initiative(ADNI)database and 63 subjects from Huashan Hospital.Subjects were classifed as T^(+)or T^(-)according to the presence or absence of tau(T)biomarkers.We used two-sample t test and one-way analysis of variance test to analyze the efect of gender with adjusting for age,years of education,and Minimum Mental State Examination.In the ADNI cohort,we found diferences in Tau deposition in fusiform gyrus,inferior temporal gyrus,middle temporal gyrus and parahippocampal gyrus between the female T^(+)(FT^(+))and male T^(+)(MT^(+))groups(p<0.05).Tau deposition did not difer signifcantly between female T^(-)(FT^(-))and male T^(-)(MT^(-))subjects(p>0.05).In the Huashan Hospital cohort,there was no diference in Tau deposition between FT^(+)and MT^(+)(p>0.05).The results show that tau depositions signifcantly increased in females in above brain regions.Our fndings suggest that tau deposition is infuenced by gender in the A+subjects.This result has important clinical implications for the development of gender-guided early interventions for patients with both Tau and Amyloid depositions.

Identification of Germline Mutations in East‑Asian Young Never‑Smokers with Lung Adenocarcinoma by Whole‑Exome Sequencing

Recently,an increasing number of young never-smokers are diagnosed with lung cancer.The aim of this study is to investigate the genetic predisposition of lung cancer in these patients and discover candidate pathogenic variants for lung adenocarcinoma in young never-smokers.Peripheral blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of 40.Whole-exome sequencing(WES)was conducted on genomic DNA extracted from peripheral blood cells.As a result,3,481 single nucleotide variants were identified.By bioinformatical tools and the published gene list associated with genetic predisposition of cancer,pathogenic variants were detected in ten germline genes:ATR,FANCD2,FANCE,GATA2,HFE,MSH2,PDGFRA,PMS2,SDHB,and WAS.Patients with pathogenic variants were more likely to occur in females(9/10,90.0%)and have stage IV lung adenocarcinoma(4/10,40%).Furthermore,germline muta-tions in 17 genes(ASB18,B3GALT5,CLEC4F,COL6A6,CYP4B1,C6orf132,EXO1,GATA4,HCK,KCP,NPHP4,PIGX,PPIL2,PPP1R3G,RRBP1,SALL4,and TTC28),which occurred in at least two patients,displayed potentially pathogenic effects.Gene ontology analysis further showed that these genes with germline mutations were mainly located in nucleo-plasm and associated with DNA repair-related biological processes.The study provides spectrum of pathogenic variants and functional explanation for genetic predisposition of lung adenocarcinoma in young never-smokers,which sheds a light on prevention and early diagnosis of lung cancer.

Deep Immunophenotyping of Human Whole Blood by Standardized Multi‑parametric Flow Cytometry Analyses

Immunophenotyping is proving crucial to understanding the role of the immune system in health and disease.High-through-put flow cytometry has been used extensively to reveal changes in immune cell composition and function at the single-cell level.Here,we describe six optimized 11-color flow cytometry panels for deep immunophenotyping of human whole blood.A total of 51 surface antibodies,which are readily available and validated,were selected to identify the key immune cell populations and evaluate their functional state in a single assay.The gating strategies for effective flow cytometry data analysis are included in the protocol.To ensure data reproducibility,we provide detailed procedures in three parts,including(1)instrument characterization and detector gain optimization,(2)antibody titration and sample staining,and(3)data acquisition and quality checks.This standardized approach has been applied to a variety of donors for a better understanding of the complexity of the human immune system.

Immune‑Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults

Ageing is often accompanied with a decline in immune system function,resulting in immune ageing.Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence.The change in immune phenotype is a key indication of the diseased or healthy status.However,the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed.Here,we analysed T and natural killer(NK)cell subsets,the phenotype and cell differentiation states in 43,096 healthy individuals,aged 20–88 years,without known diseases.Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals.The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis.Our initial analysis and machine modelling prediction showed that na.ve T cells decreased with ageing,whereas central memory T cells(Tcm)and effector memory T cells(Tem)increased cluster of differentiation(CD)28-associated T cells.This is the largest study to investigate the correlation between age and immune cell function in a Chinese population,and provides insightful differences,suggesting that healthy adults might be considerably influenced by age and sex.The age of a person's immune system might be different from their chronological age.Our immune-ageing modelling study is one of the largest studies to provide insights into‘immune-age’rather than‘biological-age’.Through machine learning,we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction.Our research not only reveals the impact of age on immune parameter differences within the Chinese population,but also provides new insights for monitoring and preventing some diseases in clinical practice.

Measurement of Cerebral Oxygen Extraction Fraction Using Quantitative BOLD Approach:A Review

Quantification of brain oxygenation and metabolism,both of which are indicators of the level of brain activity,plays a vital role in understanding the cerebral perfusion and the pathophysiology of brain disorders.Magnetic resonance imaging(MRI),a widely used clinical imaging technique,which is very sensitive to magnetic susceptibility,has the possibility of substitut-ing positron emission tomography(PET)in measuring oxygen metabolism.This review mainly focuses on the quantitative blood oxygenation level-dependent(qBOLD)method for the evaluation of oxygen extraction fraction(OEF)in the brain.Here,we review the theoretic basis of qBOLD,as well as existing acquisition and quantification methods.Some published clinical studies are also presented,and the pros and cons of qBOLD method are discussed as well.

A Genome‑Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes

High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution.To identify novel susceptibility genes for axial length(AL)in highly myopic eyes,a genome-wide association study(GWAS)was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients.Top single nucleotide polymorphisms(SNPs)were functionally annotated.Immunofluorescence staining,quantitative polymerase chain reaction,and western blot were performed using neural retina of form-deprived myopic mice.Enrichment analyses were further performed.We identified the four top SNPs and found that ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16(ADAMTS16)and Phosphatidylinositol Glycan Anchor Biosynthesis Class Z(PIGZ)had the potential of clinical signifi-cance.Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice,especially in the ganglion cell layer.The messenger RNA(mRNA)levels of both ADAMTS16 and PIGZ were significantly higher in the neural retina of form-deprived eyes(p=0.005 and 0.007 respectively),and both proteins showed significantly upregulated expression in the neural retina of deprived eyes(p=0.004 and 0.042,respectively).Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL,and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed.In conclusion,the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes.Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest.

Oral Microbiota:A New Insight into Cancer Progression,Diagnosis and Treatment

The polymorphic microbiome has been defined as one of the“Hallmarks of Cancer”.Extensive studies have now uncovered the role of oral microbiota in cancer development and progression.Bacteria,fungi,archaea,and viruses in the oral cavity interact dynamically with the oral microenvironment to maintain the oral micro-ecological homeostasis.This complex interaction is influenced by many factors,such as maternal transmission,personal factors and environmental factors.Dysbiosis of oral microbiota can disturbed this host-microbiota interaction,leading to systemic diseases.Numerous studies have shown the potential associations between oral microbiota and a variety of cancers.However,the underlying mechanisms and therapeutic insights are still poorly understood.In this review,we mainly focus on the following aspects:(1)the factors affect oral microbiota composition and function;(2)the interaction between microenvironment and oral microbiota;(3)the role of multi-kingdom oral microbiota in human health;(4)the potential underlying mechanisms and therapeutic benefits of oral microbiota against cancer.Finally,we aim to describe the impact of oral microbiota on cancer progression and provide novel therapeutic insights into cancer prevention and treatment by targeting oral microbiota.