Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase Deficiency

Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.

PCR-HRM for Genomic Surveillance of SARS-CoV-2: A Variant Detection Tool in Côte d’Ivoire, West Africa

The rise of new viruses, like SARS-CoV-2 causing the COVID-19 outbreak, along with the return of antibiotic resistance in harmful bacteria, demands a swift and efficient reaction to safeguard the health and welfare of the global population. It is crucial to have effective measures for prevention, intervention, and monitoring in place to address these evolving and recurring risks, ensuring public health and international security. In countries with limited resources, utilizing recombinant mutation plasmid technology in conjunction with PCR-HRM could help differentiate the existence of novel variants. cDNA synthesis was carried out on 8 nasopharyngeal samples following viral RNA extraction. The P1 segment of the SARS-CoV-2 Spike S protein was amplified via conventional PCR. Subsequently, PCR products were ligated with the pGEM-T Easy vector to generate eight recombinant SARS-CoV-2 plasmids. Clones containing mutations were sequenced using Sanger sequencing and analyzed through PCR-HRM. The P1 segment of the S gene from SARS-CoV-2 was successfully amplified, resulting in 8 recombinant plasmids generated from the 231 bp fragment. PCR-HRM analysis of these recombinant plasmids differentiated three variations within the SARS-CoV-2 plasmid population, each displaying distinct melting temperatures. Sanger sequencing identified mutations A112C, G113T, A114G, G214T, and G216C on the P1 segment, validating the PCR-HRM findings of the variations. These mutations led to the detection of L452R or L452M and F486V protein mutations within the protein sequence of the Omicron variant of SARS-CoV-2. In summary, PCR-HRM is a vital and affordable tool for distinguishing SARS-CoV-2 variants utilizing recombinant plasmids as controls.

Effect of Co on Solidification Characteristics and Microstructural Transformation of Non-equilibrium Solidified Cu-Ni Alloys

Non-equilibrium solidification structures of Cu55Ni45 and Cu55Ni43Co2 alloys were prepared by the molten glass purification cycle superheating method.The variation of the recalescence phenomenon with the degree of undercooling in the rapid solidification process was investigated using an infrared thermometer.The addition of the Co element affected the evolution of the recalescence phenomenon in Cu-Ni alloys.The images of the solid-liquid interface migration during the rapid solidification of supercooled melts were captured by using a high-speed camera.The solidification rate of Cu-Ni alloys,with the addition of Co elements,was explored.Finally,the grain refinement structure with low supercooling was characterised using electron backscatter diffraction(EBSD).The effect of Co on the microstructural evolution during nonequilibrium solidification of Cu-Ni alloys under conditions of small supercooling is investigated by comparing the microstructures of Cu55Ni45 and Cu55Ni43Co2 alloys.The experimental results show that the addition of a small amount of Co weakens the recalescence behaviour of the Cu55Ni45 alloy and significantly reduces the thermal strain in the rapid solidification phase.In the rapid solidification phase,the thermal strain is greatly reduced,and there is a significant increase in the characteristic undercooling degree.Furthermore,the addition of Co and the reduction of Cu not only result in a lower solidification rate of the alloy,but also contribute to the homogenisation of the grain size.

New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy

AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .

RDH12-associated retinal degeneration caused by a homozygous pathogenic variant of 146C>T and literature review

AIM:To describe the clinical,electrophysiological,and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant.METHODS:The patient underwent a complete ophthalmologic examination including best-corrected visual acuity,anterior segment and dilated fundus,visual field,spectral-domain optical coherence tomography(OCT)and electroretinogram(ERG).The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result.Then we reviewed the characteristics of the patients reported with the same variant.RESULTS:A 30-year male presented with severe early retinal degeneration who complained night blindness,decreased visual acuity,vitreous floaters and amaurosis fugax.The best corrected vision was 0.04 OD and 0.12 OS,respectively.The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye.Autofluorescence shows bilateral symmetrical hypo-autofluorescence.ERG revealed that the amplitudes of a-and b-wave were severely decreased.Multifocal ERG showed decreased amplitudes in the local macular area.A homozygous missense variant c.146C>T(chr14:68191267)was found.The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied.CONCLUSION:An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported.The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

Audio2AB:Audio-driven collaborative generation of virtual character animation

Background Considerable research has been conducted in the areas of audio-driven virtual character gestures and facial animation with some degree of success.However,few methods exist for generating full-body animations,and the portability of virtual character gestures and facial animations has not received sufficient attention.Methods Therefore,we propose a deep-learning-based audio-to-animation-and-blendshape(Audio2AB)network that generates gesture animations and ARK it's 52 facial expression parameter blendshape weights based on audio,audio-corresponding text,emotion labels,and semantic relevance labels to generate parametric data for full-body animations.This parameterization method can be used to drive full-body animations of virtual characters and improve their portability.In the experiment,we first downsampled the gesture and facial data to achieve the same temporal resolution for the input,output,and facial data.The Audio2AB network then encoded the audio,audio-corresponding text,emotion labels,and semantic relevance labels,and then fused the text,emotion labels,and semantic relevance labels into the audio to obtain better audio features.Finally,we established links between the body,gestures,and facial decoders and generated the corresponding animation sequences through our proposed GAN-GF loss function.Results By using audio,audio-corresponding text,and emotional and semantic relevance labels as input,the trained Audio2AB network could generate gesture animation data containing blendshape weights.Therefore,different 3D virtual character animations could be created through parameterization.Conclusions The experimental results showed that the proposed method could generate significant gestures and facial animations.

Isolated Hyperacute T-Waves in West Nile Encephalitis Indicating Atypical Variant of Stress-Induced Cardiomyopathy

Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.

Functional analysis of the novel mitochondrial tRNA^(Trp)and tRNA^(Ser(AGY))variants associated with type 2 diabetes mellitus

BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Left lower lobe sleeve resection for the clear cell variant of pulmonary mucoepidermoid carcinoma:A case report

BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.

Frontier Progress of Landscape Character Assessment in China

The role of Landscape Character Assessment(LCA)at the level of territorial landscape governance spans both natural and social sciences.By analyzing the development history,research distribution,methods and applications of cutting-edge cases of LCA in China,the following conclusions are drawn:①the LCA research in China originated earlier than that in Europe,but has not yet been systematically applied to the implementation of urban and rural planning at all levels;②the fundamental theory of LCA in China has been well constructed,with three main research directions:technologyled,assessment-led,and assessment combined with other theories;③the development of LCA in rural areas is more mature than in urban areas,but the progress of research is uneven across regions;④the current research presents significant“bottom-up”academic characteristics,and there is an urgent need for government decision-making authorities and academia to jointly promote a“top-down”standardized governance mechanism to comprehensively promote the modernization of territorial landscape governance.

Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults:A retrospective study

BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

On Nonce Variant of English Idioms

English idiom variant refers to the form of idiom created by means of altering some original components,structures,or meanings of the former idioms.The nonce variant of English idioms can be analyzed from the following three aspects:reasons for formation of nonce variant,types into which it could be divided,and rhetorical functions it is capable of producing.Through the analysis of these three aspects,it is almost likely for language-users to realize the importance and modes of idiom’s renovation,get a better understanding of English idioms,and thus utilize English idioms more skillfully.

Genomic Profile of SARS-COV-2 Associated with COVID-19 Outbreaks in N’Djamena, Chad

Background: SARS-CoV-2 has circulated worldwide with dramatic consequences. In Chad, we have no data reported of variants. The aim of this study was to identify the SARS-CoV-2 variants that circulated during the epidemic from 2020 to 2021. Methods: This is a cross-sectional, descriptive study carried out between 2020 and 2021. Samples from patients with suspected COVID-19 were tested in five laboratories in N’Djamena. One hundred quality samples of the positives were sequenced in Kinshasa using Oxford nanopore technologies minion and the Protocol Midnight SARS-CoV2. Data were processed using Excel version 16 software. Results: Of the 100 samples sequenced, 77 (77%) produced sequences, 23 (23%) did not. The genomic profiles were wild-type Wuhan and minor mutations (19A, 19B (A), 20A (B.1, B.2), 20B (AV.1), 20D (B.1.1.1 /C.36), 20C), variant of concern Alpha (20I), variant of concern Delta (21A/J), variant of interest Eta (21D), variant of concern Omicron (21K) and unclassified variant under surveillance (B.1.640). Of these variants, the maximums were detected in patients aged 26 - 35 with 30.26% and 25.26% in 36 - 45. However, 24.67% were in travelers and 75.32% in residents, 35.06% in those vaccinated against COVID-19 and 62.33% in non-vaccinates. The estimated case-fatality rate was 2.44% (107/4374). Conclusion: This work has provided preliminary data on COVID-19 and SARS-CoV-2 variants circulating during the 2020-2021 epidemics in Chad.

Optimised CNN Architectures for Handwritten Arabic Character Recognition

Handwritten character recognition is considered challenging compared with machine-printed characters due to the different human writing styles.Arabic is morphologically rich,and its characters have a high similarity.The Arabic language includes 28 characters.Each character has up to four shapes according to its location in the word(at the beginning,middle,end,and isolated).This paper proposed 12 CNN architectures for recognizing handwritten Arabic characters.The proposed architectures were derived from the popular CNN architectures,such as VGG,ResNet,and Inception,to make them applicable to recognizing character-size images.The experimental results on three well-known datasets showed that the proposed architectures significantly enhanced the recognition rate compared to the baseline models.The experiments showed that data augmentation improved the models’accuracies on all tested datasets.The proposed model outperformed most of the existing approaches.The best achieved results were 93.05%,98.30%,and 96.88%on the HIJJA,AHCD,and AIA9K datasets.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

A new infrageneric classification of Gastrochilus(Orchidaceae:Epidendroideae)based on molecular and morphological data

Gastrochilus is an orchid genus containing 73 species of mainly epiphytic on trees or rocks in mountain forests of tropical and subtropical Asia.Previous phylogenetic analyses and morphological assessments have failed to produce a well-resolved phylogeny at the infrageneric level.In the present study,a new infrageneric classification of Gastrochilus is proposed based on thoroughly morphological and phylogenetic analyses based on 52 species.Our phylogenetic analysis divided the genus into six sections including three new sections,G.sect.Pseudodistichi,G.sect.Brachycaules and G.sect.Acinacifolii.We also reinstate G.suavis to the specific rank.Furthermore,two new species,G.armeniacus Jun Y.Zhang,B.Xu&Yue H.Cheng and G.minjiangensis Jun Y.Zhang,B.Xu&Yue H.Cheng,are described and illustrated.A key to six sections of the genus is presented.

Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract

AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

Flower morphology of Allium(Amaryllidaceae)and its systematic significance

Allium is a complicated genus that includes approximately 1000 species.Although its morphology is well studied,the taxonomic importance of many morphological traits,including floral traits,are poorly understood.Here,we examined and measured the floral characteristics of 87 accessions of 74 Allium taxa(belonging to 30 sections and nine subgenera)from Central to Eastern Asian countries.We then examined the taxonomic relationships between select flower characteristics and a phylogenetic tree based on ITS sequences.Our results confirm that floral morphology provides key taxonomic information to assess species delimitation in Allium.We found that perianth color is an important characteristic within the subg.Melanocrommyum,Polyprason,and Reticulatobulbosa.In subg.Allium,Cepa,and Rhizirideum,significant characteristics include ovary shape,perianth shape,and inner tepal apex.For species in subg.Angunium,the key taxonomic character is ovule number(only one ovule in per locule).In the subg.Allium,Cepa,Polyprason,and Reticulatobulbosa,which belong to the third evolutionary line of Allium,hood-like appendages occur in the ovary,although these do not occur in subg.Rhizirideum.Our results also indicated that the flower morphology of several species in some sections are not clearly distinguished,e.g.,sect.Sacculiferum(subg.Cepa)and sect.Tenuissima(subg.Rhizirideum).This study provides detailed photographs and descriptions of floral characteristics and information on general distributions,habitats,and phenology of the studied taxa.