Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinom...Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].展开更多
The plasmid-expression system is routinely plagued by potential plasmid instability. Chromosomal integration is one powerful approach to overcome the problem. Herein we report a plasmid-free hyper-producer E.coli stra...The plasmid-expression system is routinely plagued by potential plasmid instability. Chromosomal integration is one powerful approach to overcome the problem. Herein we report a plasmid-free hyper-producer E.coli strain for coenzyme Q10 production. A series of integration expression vectors, pxKC3T5b and pxKT5b, were constructed for chemically inducible chromosomal evolution(multiple copy integration) and replicon-free and markerless chromosomal integration(single copy integration), respectively. A coenzyme Q10 hyper-producer Escherichia coli TBW20134 was constructed by applying chemically inducible chromosomal evolution,replicon-free and markerless chromosomal integration as well as deletion of menaquinone biosynthetic pathway.The engineered E. coli TBW20134 produced 10.7 mg per gram of dry cell mass(DCM) of coenzyme Q10 when supplemented with 0.075 g·L-1of 4-hydroxy benzoic acid; this yield is unprecedented in E. coli and close to that of the commercial producer Agrobacterium tumefaciens. With this strain, the coenzyme Q10 production capacity was very stable after 30 sequential transfers and no antibiotics were required during the fermentation process. The strategy presented may be useful as a general approach for construction of stable production strains synthesizing natural products where various copy numbers for different genes are concerned.展开更多
Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain large...Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.展开更多
Hybridization and polyploidy are key drivers of species diversity and genome variation in Lycoris,but their cytological and evolutionary consequences remain poorly understood.Here,we investigated chromosome numbers an...Hybridization and polyploidy are key drivers of species diversity and genome variation in Lycoris,but their cytological and evolutionary consequences remain poorly understood.Here,we investigated chromosome numbers and genome sizes in 64 accessions representing the morphological diversity across the genus.Chromosome numbers ranged from 12 to 33,with seven accessions newly identified,including L.chunxiaoensis(2n=33),two putative L.guangxiensis(2n=19),and fivenatural hybrids(2n=16,18,29,33).Genome sizes varied from 18.03 Gb(L.wulingensis)to 32.62 Gb(L.caldwellii).Although no significantcorrelationwas found between genome size and chromosome number across all accessions,a strong correlation within ploidy-level groups(i.e.,diploid or aneuploid)suggested roles for post-polyploid diploidization,aneuploidy,and dysploidy in speciation.Phylogenetic analyses based on chloroplast genomes and nuclear DNA sequences revealed significantdiscordance,indicating a complex reticulate evolution and historical hybridization,which may complicate morphological classification.Chromosome number aligned more closely with morphological groups,underscoring the necessity of integrating cytological,molecular,and morphological data for accurate taxonomy,particularly in largegenome taxa.Based on this evidence,we propose a putative speciation pathway involving multiple hybridization and polyploidization events,with allopolyploidy playing a predominant role.Furthermore,our results indicate that the species L.insularis and L.longifolia are geographic populations of L.sprengeri and L.aurea,respectively,and confirmedthe distribution of L.traubii and L.albiflora in China' Mainland.These findingsoffer new insights into the mechanisms underlying speciation,interspecificrelationships,and the evolutionary history of Lycoris.展开更多
Chromosomal rearrangements(CRs)often cause phenotypic variations.Although several major rearrangements have been identified in Triticeae,a comprehensive study of the order,timing,and breakpoints of CRs has not been co...Chromosomal rearrangements(CRs)often cause phenotypic variations.Although several major rearrangements have been identified in Triticeae,a comprehensive study of the order,timing,and breakpoints of CRs has not been conducted.Here,we reconstruct high-quality ancestral genomes for the most recent common ancestor(MRCA)of the Triticeae,and the MRCA of the wheat lineage(Triticum and Aegilops).The protogenes of MRCA of the Triticeae and the wheat lineage are 22,894 and 29,060,respectively,which were arranged in their ancestral order.By partitioning modern Triticeae chromosomes into sets of syntenic regions and linking each to the corresponding protochromosomes,we revisit the rye chromosome structural evolution and propose alternative evolutionary routes.The previously identified 4L/5L reciprocal translocation in rye and Triticum urartu is found to have occurred independently and is unlikely to be the result of chromosomal introgression following distant hybridization.We also clarify that the 4AL/7BS translocation in tetraploid wheat was a bidirectional rather than unidirectional translocation event.Lastly,we identify several breakpoints in protochromosomes that independently reoccur following Triticeae evolution,representing potential CR hotspots.This study demonstrates that these reconstructed ancestral genomes can serve as special comparative references and facilitate a better understanding of the evolution of structural rearrangements in Triticeae.展开更多
Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male ...Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study;41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.展开更多
Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database...Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources). We mapped fragile sites to chromosomal bands and divided the 23 chromosomes into fragile and non-fragile sites. The frequency of rearrangements at the chromosomal location of clones found to be deleted or duplicated in the array/CGH analysis, provided by DECIPHER, was compared in Chromosomal Fragile Sites vs. non-Fragile Sites of the human genome. The POSSUM Web was used to complement this study. The results indicated 1) a predominance of rearrangements in CFSs, 2) the absence of statistically significant difference between the frequency of rearrangements in common CFSs vs. rare CFSs, 3) a predominance of deletions over duplications in CFSs. These results on constitutional chromosomal rearrangements are evocative of the findings previously reported by others relatively to cancer supporting the current line of evidence and suggesting that a common mechanism can underlie the generation of constitutional and somatic rearrangements. The combination of insights obtained from our results and their interrelationships can indicate strategies by which the mechanisms can be targeted with preventive medical interventions.展开更多
Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled geno...Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled genome is essential for understanding the genetic features and biology of this animal. In this study, we used long-read single-molecule sequencing and high-throughput chromosome conformation capture (Hi-C) technology to obtain a high-qualitychromosome-scale scaffolding of the Chinese tree shrew genome. The new reference genome (KIZ version 2: TS_2.0) resolved problems in presently available tree shrew genomes and enabled accurate identification of large and complex repeat regions, gene structures, and species-specific genomic structural variants. In addition, by sequencing the genomes of six Chinese tree shrew individuals, we produced a comprehensive map of 12.8 M single nucleotide polymorphisms and confirmed that the major histocompatibility complex (MHC) loci and immunoglobulin gene family exhibited high nucleotide diversity in the tree shrew genome. We updated the tree shrew genome database (TreeshrewDB v2.0: http://www.treeshrewdb.org) to include the genome annotation information and genetic variations. The new high-quality reference genome of the Chinese tree shrew and the updated TreeshrewDB will facilitate the use of this animal in many different fields of research.展开更多
AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) status.METHODS Nineteen GC patients were classified as CIN and nonCIN type by The Cancer Genome Atlas ...AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) status.METHODS Nineteen GC patients were classified as CIN and nonCIN type by The Cancer Genome Atlas Research Group system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous metabolites of the GC tumor and its surrounding adjacent healthy tissues were identified through liquid chromatographymass spectrometry. Groups were compared by defining variable importance in projection score of > 1.2, a fold change value or its reciprocal of > 1.2, and a P value of < 0.05 as a significant difference.RESULTS In total,twelve men and seven women were enrolled, with a median age of 66 years(range, 47-87 years). The numbers of gene alterations in the CIN GC group were significantly higher than those in the non-CIN GC(32-218 vs 2-17; P < 0.0005). Compared with the adjacent healthy tissues, GC tumors demonstrated significantly higher aspartic acid, citicoline, glutamic acid, oxidized glutathione, succinyladenosine, and uridine diphosphate-Nacetylglucosamine levels, but significantly lower butyrylcarnitine, glutathione hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels(all P < 0.05). CIN tumors contained significantly higher phosphocholine and uridine 5'-monophosphate levels but significantly lower beta-citryl-L-glutamic acid levels than did non-CIN tumors(all P < 0.05). CIN GC tumors demonstrated additional altered pathways involving alanine, aspartate, and glutamate metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.CONCLUSION Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.展开更多
In order to develop more wheat-Haynaldia villosa translocations involving different chromosomes and chromosome segments of H. villosa, T. durum-H, villosa amphiploid was irradiated with ^60Co γ-rays at doses of 800, ...In order to develop more wheat-Haynaldia villosa translocations involving different chromosomes and chromosome segments of H. villosa, T. durum-H, villosa amphiploid was irradiated with ^60Co γ-rays at doses of 800, 1,200, and 1,600 rad. Pollen collected from the spikes 1, 2, and 3 days after irradiation were transferred to emasculated spikes of the common wheat cv. ‘Chinese Spring＇. Genomic in situ hybridization was used to identify wheat-H, villosa chromosome translocations in the M1 generation. Transmission of the identified translocation chromosomes was analyzed in the BC1, BC2, and BC3 generations. The results indicated that all three irradiation doses were highly efficient for inducing wheat-alien translocations without affecting the viability of the M1 seeds. Within the range of 800-1,600 rad, both the efficiency of translocation induction and the frequency of interstitial chromosome breakage-fusion increased as the irradiation dosage increased. A higher translocation induction frequency was observed using pollen collected from the spikes 1 day after irradiation over that of 2 or 3 days after irradiation. More than 70% of the translocations detected in the M1 generation were transmitted to the BC1 through the female gametes. All translocations recovered in the BC1 generation were recovered in the following BC2, and BC3 generations. The transmission ability of different translocation types in different genetic backgrounds showed an order of ‘whole-arm translocation 〉 small alien segment translocation 〉 large alien segment translocation＇, through either male or female gametes, In general, the transmission ability through the female gametes was higher than that through the male gametes. By this approach, 14 translocation lines that involved different H. villosa chromosomes have been identified in the BC3 using EST-STS markers, and eight of them were homozygous.展开更多
As a staple food crop for one-third of the world＇s population, common wheat （Triticum aestivum L., 2n = 6x = 42, AABBDD） plays an important role in humans＇ food security. However, the genetic variation of cultivat...As a staple food crop for one-third of the world＇s population, common wheat （Triticum aestivum L., 2n = 6x = 42, AABBDD） plays an important role in humans＇ food security. However, the genetic variation of cultivated wheat has been dramatically narrowed by genetic erosion under the modem cultivation system, resulting in vulnerability to biotic and abiotic stresses （Jiang et al., 1994; Friebe et al., 1996）. The wild relatives of wheat represent a large reservoir of superior genes, and transferring these alien genes to modem cultivars through chromosome engineering is a successful method of broadening the genetic diversity of wheat （Chen et al., 2003;展开更多
Transfer DNA （T-DNA） of Agrobacterium tumefaciens integration in the plant genome may lead to rearrangements of host plant chromosomal fragments, including inversions. However, there is very little information conce...Transfer DNA （T-DNA） of Agrobacterium tumefaciens integration in the plant genome may lead to rearrangements of host plant chromosomal fragments, including inversions. However, there is very little information concerning the inversion. The present study re- ports a transgenic rice line selected from a T-DNA tagged population, which displays a semi-dwarf phenotype. Molecular analysis of this mutant indicated an insertion of two tandem copies of T-DNA into a locus on the rice genome in a head to tail mode. This insertion of T-DNA resulted in the inversion of a 4.9 Mb chromosomal segment. Results of sequence analysis suggest that the chromosomal inversion resulted from the insertion of T-DNA with the help of sequence microhomology between insertion region of T-DNA and target sequence of the host plant.展开更多
In this study, freeze-dried water extract from the leaves of Myristica fragrans （Houtt.） was tested for mutagenic and antimutagenic potentials using the Allium cepa assay. Freeze-dried water extract alone and its co...In this study, freeze-dried water extract from the leaves of Myristica fragrans （Houtt.） was tested for mutagenic and antimutagenic potentials using the Allium cepa assay. Freeze-dried water extract alone and its combination with cyclophosphamide （CP） （50 mg/kg） were separately dissolved in tap water at 500, 1000, 2000, and 4000 mg/kg. Onions （A. cepa） were suspended in the solutions and controls for 48 h in the dark. Root tips were prepared for microscopic evaluation. 2,2-Diphenyl-l-picrylhydrazyl （DPPH） free radicals＇ scavenging power of the extract was tested using butylated hydroxyanisole （BHA） and butylated hydroxytoluene （BHT） as standards. Water extract of Myristica fragrans scavenged free radicals better than BHA, but worse than BHT. The extract alone, as well as in combination with CP suppressed cell division, and induced chromosomal aberrations that were insignificantly different from the negative control （P≤0.05）. However, cytotoxic and mutagenic actions of CP were considerably suppressed. The observed effects on cell division and chromosomes of A. cepa may be principally connected to the antioxidant properties of the extract. The obtained results suggest mitodepressive and antimutagenic potentials of water extract of the leaves of M. fragrans as desirable properties of a promising anticancer agent.展开更多
GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI ...GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI contributes to at least fifty percent of GPX activity in rodent small intestmal epithelium. The total GPX activity consists of at least 70% of selenium-dependent GPX activity in this compartment.By analyzing a panel of mouse mterspecies DNA from the Jackson Laboratory's backcross resource,we mapped Gpx2 gene to mouse chromosome 12 between D12Mit4 and D12Mit5, near the Ccs1 locus which contains a colon cancer susceptibility gene. A pseudogene, Gpx2-ps is mapped to mouse chromosome 7.Comparison of Gpx2 gene expression in three pairs of C57BL/6Ha and ICR/Ha mice which are respectively resistant and sensitive to dimethylhydrazine-induced colon cancer, we found a higher Gpx2 mRNA level in C57BL/6Ha colon than ICR/Ha colon. Interestingly, a lower level of GPX activity is found in the resistant strain of mice. Because GPX-1 has three times higher specific activity than GPX GI, our data suggest that the decreased GPX activity may result from a higher level of Gpx2 gene expression in those cells co-express GPx1 gene展开更多
Turmeric has long been used as a spice and food colouring agent in Asia. In the present investigation, the antimutagenic potential of curcumin was evaluated in Allium cepa root meristem cells. So far there is no repor...Turmeric has long been used as a spice and food colouring agent in Asia. In the present investigation, the antimutagenic potential of curcumin was evaluated in Allium cepa root meristem cells. So far there is no report on the biological properties of curcumin in plant test systems. The root tip cells were treated with sodium azide at 200 and 300 μg/ml for 3 h and curcumin was given at 5, 10 and 20 μg/ml for 16 h, prior to sodium azide treatment. The tips were squashed after colchicine treatment and the cells were analyzed for chromosome aberration and mitotic index. Curcumin induces chromosomal aberration in Allium cepa root tip cells in an insignificant manner, when compared with untreated control. Sodium azide alone induces chromosomal aberrations significantly with increasing concentrations. The total number of aberrations was significantly reduced in root tip cells pretreated with curcumin. The study reveals that curcumin has antimutagenic potential against sodium azide induced chromosomal aberrations in Allium cepa root meristem cells. In addition, it showed mild cytotoxicity by reducing the percentage of mitotic index in all curcumin treated groups, but the mechanism of action remains unknown. The antimutagenic potential of curcumin is effective at 5 μg/ml in Allium cepa root meristem cells.展开更多
A backcross recombinant inbred line population consisting of 202 lines was developed from Xieqingzao B//Xieqingzao B / Dongxiang wild rice. The population was assayed with DNA markers and phenotyped on planthopper res...A backcross recombinant inbred line population consisting of 202 lines was developed from Xieqingzao B//Xieqingzao B / Dongxiang wild rice. The population was assayed with DNA markers and phenotyped on planthopper resistance and yield traits. A linkage map consisting of 119 DNA markers and spanned for 1188 cM over the 12 rice chromosomes was constructed. Thirty-two chromosomal segment substitution lines were selected based on the percentage of Xieqingzao B allele at marker loci. These lines are of great potential for gene mapping and alien gene introgression.展开更多
Cotton fibers are the main raw materials of the textile industry.Exogenous superior fiber genes have been introduced into upland cotton to develop high-yield cultivars with excellent fiber quality.We used a single chr...Cotton fibers are the main raw materials of the textile industry.Exogenous superior fiber genes have been introduced into upland cotton to develop high-yield cultivars with excellent fiber quality.We used a single chromosomal segment on the chromosome A07 substitution line SL7,with high fiber strength,to investigate the molecular mechanism underlying its fiber quality.RNA-seq and KEGG analysis showed that 70 differentially expressed genes were enriched in plant hormone transduction pathways,including auxin,ethylene and abscisic acid,in fibers at 10 days post-anthesis(DPA).Among these,fiberdevelopment related transcription factors MYB and NAC,including Gh_A11G0981(MYB108),Gh_A03G0887(NAC029),and Gh_A08G1691(NAC021),were significantly upregulated in SL7,as were numerous cellulose synthase-like(CSL)genes involved in non-cellulose polysaccharide and cell wall synthesis.The hemicellulose content of SL7 was significantly higher than that of L22,an upland cotton cultivar.These results suggest that key genes in the introgressed chromosomal segment of SL7 regulate the expression of transcription-factor genes via hormone-transduction pathways,thereby inducing the expression of genes involved in secondary wall synthesis and ultimately improving fiber quality.This study has shed light on the molecular mechanism of fiber development and will contribute to the improvement of fiber quality of upland cotton by molecular breeding.展开更多
Chinese shrimp （Fenneropenaeus chinensis） is an economically important aquaculture species in China. However, cytogenetic and genomic data is limited in the organism partly because the chromosomes are difficult to i...Chinese shrimp （Fenneropenaeus chinensis） is an economically important aquaculture species in China. However, cytogenetic and genomic data is limited in the organism partly because the chromosomes are difficult to isolate and analyze. In this study, fluorescence in-situ hybridization （FISH） was used to identify the chromosomes of F. chinensis. The 5S ribosomal RNA gene （rDNA） of F. chinensis was isolated, cloned and then used as a hybridization probe. The results show that the 5S rDNA was located on one pair of homologous chromosomes in F chinensis. In addition, triploid shrimp were used to evaluate the feasibility of chromosome identification using FISH and to validate the method. It was confirmed that 5S rDNA can be used as a chromosome-specific probe for chromosome identification in E chinensis. The successful application ofFISH in E chinensis shows that chromosome-specific probes can be developed and this finding will facilitate further research on the chromosomes ofpenaeid shrimps.展开更多
One of the impediments in the genetic improvement of cotton fiber is the paucity of information about genes associated with fiber development.Availability of chromosome arm substitution line CS-
Objective:Chromosomal instability(CIN)is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes,frequently observed in cancer cell populations and is associated with p...Objective:Chromosomal instability(CIN)is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes,frequently observed in cancer cell populations and is associated with poor prognosis,metastasis,and therapeutic resistance.Breast cancer(BC)is characterized by unstable karyotypes and recent reports have indicated that CIN may influence the response of BC to chemotherapy regimens.However,paradoxical associations between extreme CIN and improved outcome have been observed.Methods:This study aimed to 1)evaluate CIN levels and clonal heterogeneity(CH)in MCF7,ZR-751,MDA-MB468,BT474,and KPL4 BC cells treated with low doses of tamoxifen(TAM),docetaxel(DOC),doxorubicin(DOX),Herceptin(HT),and combined treatments(TAM/DOC,TAM/DOX,TAM/HT,HT/DOC,and HT/DOX)by using fluorescence in situ hybridization(FISH),and 2)examine the association with response to treatments by comparing FISH results with cell proliferation.Results:Intermediate CIN was linked to drug sensitivity according to three characteristics:estrogen receptorα(ERα)and HER2 status,pre-existing CIN level in cancer cells,and the CIN induced by the treatments.ERα+/HER2-cells with intermediate CIN were sensitive to treatment with taxanes(DOC)and anthracyclines(DOX),while ERα-/HER2-,ERα+/HER2+,and ERα-/HER2+cells with intermediate CIN were resistant to these treatments.Conclusions:A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes.展开更多
基金support through Manipal University Jaipur for the Enhanced Seed Grant under the Endowment Fund(Grant No.E3/2023-24/QE-04-05).
文摘Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].
基金Supported by the National Natural Science Foundation of China(30970089,20876181,21276289)the Natural Science Foundation of Guangdong Province(9351027501000003,S2011010001396)
文摘The plasmid-expression system is routinely plagued by potential plasmid instability. Chromosomal integration is one powerful approach to overcome the problem. Herein we report a plasmid-free hyper-producer E.coli strain for coenzyme Q10 production. A series of integration expression vectors, pxKC3T5b and pxKT5b, were constructed for chemically inducible chromosomal evolution(multiple copy integration) and replicon-free and markerless chromosomal integration(single copy integration), respectively. A coenzyme Q10 hyper-producer Escherichia coli TBW20134 was constructed by applying chemically inducible chromosomal evolution,replicon-free and markerless chromosomal integration as well as deletion of menaquinone biosynthetic pathway.The engineered E. coli TBW20134 produced 10.7 mg per gram of dry cell mass(DCM) of coenzyme Q10 when supplemented with 0.075 g·L-1of 4-hydroxy benzoic acid; this yield is unprecedented in E. coli and close to that of the commercial producer Agrobacterium tumefaciens. With this strain, the coenzyme Q10 production capacity was very stable after 30 sequential transfers and no antibiotics were required during the fermentation process. The strategy presented may be useful as a general approach for construction of stable production strains synthesizing natural products where various copy numbers for different genes are concerned.
文摘Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.
基金supported by the ScientificFund of Nanjing Botanical Garden Men.Sun Yat-Sen(JSPKLB202519)Jiangsu Provincial Crop Germplasm Resource Bank(Lycoris)(JS-ZW-K04)Forestry Science and Technology Popularization Demonstration Project of the Central Finance[Su(2024)TG06].
文摘Hybridization and polyploidy are key drivers of species diversity and genome variation in Lycoris,but their cytological and evolutionary consequences remain poorly understood.Here,we investigated chromosome numbers and genome sizes in 64 accessions representing the morphological diversity across the genus.Chromosome numbers ranged from 12 to 33,with seven accessions newly identified,including L.chunxiaoensis(2n=33),two putative L.guangxiensis(2n=19),and fivenatural hybrids(2n=16,18,29,33).Genome sizes varied from 18.03 Gb(L.wulingensis)to 32.62 Gb(L.caldwellii).Although no significantcorrelationwas found between genome size and chromosome number across all accessions,a strong correlation within ploidy-level groups(i.e.,diploid or aneuploid)suggested roles for post-polyploid diploidization,aneuploidy,and dysploidy in speciation.Phylogenetic analyses based on chloroplast genomes and nuclear DNA sequences revealed significantdiscordance,indicating a complex reticulate evolution and historical hybridization,which may complicate morphological classification.Chromosome number aligned more closely with morphological groups,underscoring the necessity of integrating cytological,molecular,and morphological data for accurate taxonomy,particularly in largegenome taxa.Based on this evidence,we propose a putative speciation pathway involving multiple hybridization and polyploidization events,with allopolyploidy playing a predominant role.Furthermore,our results indicate that the species L.insularis and L.longifolia are geographic populations of L.sprengeri and L.aurea,respectively,and confirmedthe distribution of L.traubii and L.albiflora in China' Mainland.These findingsoffer new insights into the mechanisms underlying speciation,interspecificrelationships,and the evolutionary history of Lycoris.
基金CAs Youth Interdisciplinary Team(JCTD-2022-06)the National Nature Science Foundation of China(31870209).
文摘Chromosomal rearrangements(CRs)often cause phenotypic variations.Although several major rearrangements have been identified in Triticeae,a comprehensive study of the order,timing,and breakpoints of CRs has not been conducted.Here,we reconstruct high-quality ancestral genomes for the most recent common ancestor(MRCA)of the Triticeae,and the MRCA of the wheat lineage(Triticum and Aegilops).The protogenes of MRCA of the Triticeae and the wheat lineage are 22,894 and 29,060,respectively,which were arranged in their ancestral order.By partitioning modern Triticeae chromosomes into sets of syntenic regions and linking each to the corresponding protochromosomes,we revisit the rye chromosome structural evolution and propose alternative evolutionary routes.The previously identified 4L/5L reciprocal translocation in rye and Triticum urartu is found to have occurred independently and is unlikely to be the result of chromosomal introgression following distant hybridization.We also clarify that the 4AL/7BS translocation in tetraploid wheat was a bidirectional rather than unidirectional translocation event.Lastly,we identify several breakpoints in protochromosomes that independently reoccur following Triticeae evolution,representing potential CR hotspots.This study demonstrates that these reconstructed ancestral genomes can serve as special comparative references and facilitate a better understanding of the evolution of structural rearrangements in Triticeae.
基金supported by the National Natural Science Foundation of China(No.32070582)the Joint Foundation of He Lin Academical Workstation of the Third Affiliated Hospital of Guangzhou Medical University(2023HLLH01)the Plan on enhancing scientific research in GMU(2024SRP125).
文摘Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study;41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
基金partially supported by CIGMH/FCM/UNL,under the project PEST-OE/SAU/UI0009/2011CMA/FCT/UNL,under the project PEst-OE/MAT/UI0297/2011.
文摘Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources). We mapped fragile sites to chromosomal bands and divided the 23 chromosomes into fragile and non-fragile sites. The frequency of rearrangements at the chromosomal location of clones found to be deleted or duplicated in the array/CGH analysis, provided by DECIPHER, was compared in Chromosomal Fragile Sites vs. non-Fragile Sites of the human genome. The POSSUM Web was used to complement this study. The results indicated 1) a predominance of rearrangements in CFSs, 2) the absence of statistically significant difference between the frequency of rearrangements in common CFSs vs. rare CFSs, 3) a predominance of deletions over duplications in CFSs. These results on constitutional chromosomal rearrangements are evocative of the findings previously reported by others relatively to cancer supporting the current line of evidence and suggesting that a common mechanism can underlie the generation of constitutional and somatic rearrangements. The combination of insights obtained from our results and their interrelationships can indicate strategies by which the mechanisms can be targeted with preventive medical interventions.
基金supported by the National Natural Science Foundation of China(U1402224,31601010,81571998,and U1702284)Yunnan Province(2015HA038 and 2018FB054)Chinese Academy of Sciences(CAS zsys-02)
文摘Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled genome is essential for understanding the genetic features and biology of this animal. In this study, we used long-read single-molecule sequencing and high-throughput chromosome conformation capture (Hi-C) technology to obtain a high-qualitychromosome-scale scaffolding of the Chinese tree shrew genome. The new reference genome (KIZ version 2: TS_2.0) resolved problems in presently available tree shrew genomes and enabled accurate identification of large and complex repeat regions, gene structures, and species-specific genomic structural variants. In addition, by sequencing the genomes of six Chinese tree shrew individuals, we produced a comprehensive map of 12.8 M single nucleotide polymorphisms and confirmed that the major histocompatibility complex (MHC) loci and immunoglobulin gene family exhibited high nucleotide diversity in the tree shrew genome. We updated the tree shrew genome database (TreeshrewDB v2.0: http://www.treeshrewdb.org) to include the genome annotation information and genetic variations. The new high-quality reference genome of the Chinese tree shrew and the updated TreeshrewDB will facilitate the use of this animal in many different fields of research.
基金Supported by the Ministry of Science and Technology Taiwan grant,No.MOST 106-2314-B-182A-019-MY3the Chang Gung Foundation,No.CMRPG3E1321-2,No.IRB201601916B0,and No.IRB103-7448B
文摘AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) status.METHODS Nineteen GC patients were classified as CIN and nonCIN type by The Cancer Genome Atlas Research Group system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous metabolites of the GC tumor and its surrounding adjacent healthy tissues were identified through liquid chromatographymass spectrometry. Groups were compared by defining variable importance in projection score of > 1.2, a fold change value or its reciprocal of > 1.2, and a P value of < 0.05 as a significant difference.RESULTS In total,twelve men and seven women were enrolled, with a median age of 66 years(range, 47-87 years). The numbers of gene alterations in the CIN GC group were significantly higher than those in the non-CIN GC(32-218 vs 2-17; P < 0.0005). Compared with the adjacent healthy tissues, GC tumors demonstrated significantly higher aspartic acid, citicoline, glutamic acid, oxidized glutathione, succinyladenosine, and uridine diphosphate-Nacetylglucosamine levels, but significantly lower butyrylcarnitine, glutathione hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels(all P < 0.05). CIN tumors contained significantly higher phosphocholine and uridine 5'-monophosphate levels but significantly lower beta-citryl-L-glutamic acid levels than did non-CIN tumors(all P < 0.05). CIN GC tumors demonstrated additional altered pathways involving alanine, aspartate, and glutamate metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.CONCLUSION Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.
基金supported by the National Natural Science Foundation of China (No.30270827 and 30871519)the High Tech Program of China (No.2006AA100101,2006AA10Z1F6)the Ministry of Educate 111 Project (B08025)
文摘In order to develop more wheat-Haynaldia villosa translocations involving different chromosomes and chromosome segments of H. villosa, T. durum-H, villosa amphiploid was irradiated with ^60Co γ-rays at doses of 800, 1,200, and 1,600 rad. Pollen collected from the spikes 1, 2, and 3 days after irradiation were transferred to emasculated spikes of the common wheat cv. ‘Chinese Spring＇. Genomic in situ hybridization was used to identify wheat-H, villosa chromosome translocations in the M1 generation. Transmission of the identified translocation chromosomes was analyzed in the BC1, BC2, and BC3 generations. The results indicated that all three irradiation doses were highly efficient for inducing wheat-alien translocations without affecting the viability of the M1 seeds. Within the range of 800-1,600 rad, both the efficiency of translocation induction and the frequency of interstitial chromosome breakage-fusion increased as the irradiation dosage increased. A higher translocation induction frequency was observed using pollen collected from the spikes 1 day after irradiation over that of 2 or 3 days after irradiation. More than 70% of the translocations detected in the M1 generation were transmitted to the BC1 through the female gametes. All translocations recovered in the BC1 generation were recovered in the following BC2, and BC3 generations. The transmission ability of different translocation types in different genetic backgrounds showed an order of ‘whole-arm translocation 〉 small alien segment translocation 〉 large alien segment translocation＇, through either male or female gametes, In general, the transmission ability through the female gametes was higher than that through the male gametes. By this approach, 14 translocation lines that involved different H. villosa chromosomes have been identified in the BC3 using EST-STS markers, and eight of them were homozygous.
基金supported by a grant from the National High Technology Research and Development Program("863" Program) of China(No. 2011AA100103)
文摘As a staple food crop for one-third of the world＇s population, common wheat （Triticum aestivum L., 2n = 6x = 42, AABBDD） plays an important role in humans＇ food security. However, the genetic variation of cultivated wheat has been dramatically narrowed by genetic erosion under the modem cultivation system, resulting in vulnerability to biotic and abiotic stresses （Jiang et al., 1994; Friebe et al., 1996）. The wild relatives of wheat represent a large reservoir of superior genes, and transferring these alien genes to modem cultivars through chromosome engineering is a successful method of broadening the genetic diversity of wheat （Chen et al., 2003;
基金supported by the National High Technology Development Program of China (No.2008AA10Z104)China Postdoctoral Science Foundation (No.20060600519)
文摘Transfer DNA （T-DNA） of Agrobacterium tumefaciens integration in the plant genome may lead to rearrangements of host plant chromosomal fragments, including inversions. However, there is very little information concerning the inversion. The present study re- ports a transgenic rice line selected from a T-DNA tagged population, which displays a semi-dwarf phenotype. Molecular analysis of this mutant indicated an insertion of two tandem copies of T-DNA into a locus on the rice genome in a head to tail mode. This insertion of T-DNA resulted in the inversion of a 4.9 Mb chromosomal segment. Results of sequence analysis suggest that the chromosomal inversion resulted from the insertion of T-DNA with the help of sequence microhomology between insertion region of T-DNA and target sequence of the host plant.
文摘In this study, freeze-dried water extract from the leaves of Myristica fragrans （Houtt.） was tested for mutagenic and antimutagenic potentials using the Allium cepa assay. Freeze-dried water extract alone and its combination with cyclophosphamide （CP） （50 mg/kg） were separately dissolved in tap water at 500, 1000, 2000, and 4000 mg/kg. Onions （A. cepa） were suspended in the solutions and controls for 48 h in the dark. Root tips were prepared for microscopic evaluation. 2,2-Diphenyl-l-picrylhydrazyl （DPPH） free radicals＇ scavenging power of the extract was tested using butylated hydroxyanisole （BHA） and butylated hydroxytoluene （BHT） as standards. Water extract of Myristica fragrans scavenged free radicals better than BHA, but worse than BHT. The extract alone, as well as in combination with CP suppressed cell division, and induced chromosomal aberrations that were insignificantly different from the negative control （P≤0.05）. However, cytotoxic and mutagenic actions of CP were considerably suppressed. The observed effects on cell division and chromosomes of A. cepa may be principally connected to the antioxidant properties of the extract. The obtained results suggest mitodepressive and antimutagenic potentials of water extract of the leaves of M. fragrans as desirable properties of a promising anticancer agent.
文摘GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI contributes to at least fifty percent of GPX activity in rodent small intestmal epithelium. The total GPX activity consists of at least 70% of selenium-dependent GPX activity in this compartment.By analyzing a panel of mouse mterspecies DNA from the Jackson Laboratory's backcross resource,we mapped Gpx2 gene to mouse chromosome 12 between D12Mit4 and D12Mit5, near the Ccs1 locus which contains a colon cancer susceptibility gene. A pseudogene, Gpx2-ps is mapped to mouse chromosome 7.Comparison of Gpx2 gene expression in three pairs of C57BL/6Ha and ICR/Ha mice which are respectively resistant and sensitive to dimethylhydrazine-induced colon cancer, we found a higher Gpx2 mRNA level in C57BL/6Ha colon than ICR/Ha colon. Interestingly, a lower level of GPX activity is found in the resistant strain of mice. Because GPX-1 has three times higher specific activity than GPX GI, our data suggest that the decreased GPX activity may result from a higher level of Gpx2 gene expression in those cells co-express GPx1 gene
基金Project (No. SP/SO/HS-21/2002) supported by the Department of Science and Technology, Government of India, New Delhi
文摘Turmeric has long been used as a spice and food colouring agent in Asia. In the present investigation, the antimutagenic potential of curcumin was evaluated in Allium cepa root meristem cells. So far there is no report on the biological properties of curcumin in plant test systems. The root tip cells were treated with sodium azide at 200 and 300 μg/ml for 3 h and curcumin was given at 5, 10 and 20 μg/ml for 16 h, prior to sodium azide treatment. The tips were squashed after colchicine treatment and the cells were analyzed for chromosome aberration and mitotic index. Curcumin induces chromosomal aberration in Allium cepa root tip cells in an insignificant manner, when compared with untreated control. Sodium azide alone induces chromosomal aberrations significantly with increasing concentrations. The total number of aberrations was significantly reduced in root tip cells pretreated with curcumin. The study reveals that curcumin has antimutagenic potential against sodium azide induced chromosomal aberrations in Allium cepa root meristem cells. In addition, it showed mild cytotoxicity by reducing the percentage of mitotic index in all curcumin treated groups, but the mechanism of action remains unknown. The antimutagenic potential of curcumin is effective at 5 μg/ml in Allium cepa root meristem cells.
文摘A backcross recombinant inbred line population consisting of 202 lines was developed from Xieqingzao B//Xieqingzao B / Dongxiang wild rice. The population was assayed with DNA markers and phenotyped on planthopper resistance and yield traits. A linkage map consisting of 119 DNA markers and spanned for 1188 cM over the 12 rice chromosomes was constructed. Thirty-two chromosomal segment substitution lines were selected based on the percentage of Xieqingzao B allele at marker loci. These lines are of great potential for gene mapping and alien gene introgression.
基金the National Natural Science Foundation of China(31601345 and 31671742)the Earmarked Fund for China Agriculture Research System(CARS-15-05)+1 种基金the Taishan Scholar Project of Shandong Province(ts201511070)the Innovation Project in Shandong Academy of Agricultural Sciences(CXGC2016A01).
文摘Cotton fibers are the main raw materials of the textile industry.Exogenous superior fiber genes have been introduced into upland cotton to develop high-yield cultivars with excellent fiber quality.We used a single chromosomal segment on the chromosome A07 substitution line SL7,with high fiber strength,to investigate the molecular mechanism underlying its fiber quality.RNA-seq and KEGG analysis showed that 70 differentially expressed genes were enriched in plant hormone transduction pathways,including auxin,ethylene and abscisic acid,in fibers at 10 days post-anthesis(DPA).Among these,fiberdevelopment related transcription factors MYB and NAC,including Gh_A11G0981(MYB108),Gh_A03G0887(NAC029),and Gh_A08G1691(NAC021),were significantly upregulated in SL7,as were numerous cellulose synthase-like(CSL)genes involved in non-cellulose polysaccharide and cell wall synthesis.The hemicellulose content of SL7 was significantly higher than that of L22,an upland cotton cultivar.These results suggest that key genes in the introgressed chromosomal segment of SL7 regulate the expression of transcription-factor genes via hormone-transduction pathways,thereby inducing the expression of genes involved in secondary wall synthesis and ultimately improving fiber quality.This study has shed light on the molecular mechanism of fiber development and will contribute to the improvement of fiber quality of upland cotton by molecular breeding.
基金Supported by the Key Program of the National Natural ScienceFoundation of China(No.30730071)the National High-Tech Researchand Development Program of China(863 program)(No.2007AA09Z430)the General Program of National Natural Science Foundation of China(Nos.30471347&40706048)
文摘Chinese shrimp （Fenneropenaeus chinensis） is an economically important aquaculture species in China. However, cytogenetic and genomic data is limited in the organism partly because the chromosomes are difficult to isolate and analyze. In this study, fluorescence in-situ hybridization （FISH） was used to identify the chromosomes of F. chinensis. The 5S ribosomal RNA gene （rDNA） of F. chinensis was isolated, cloned and then used as a hybridization probe. The results show that the 5S rDNA was located on one pair of homologous chromosomes in F chinensis. In addition, triploid shrimp were used to evaluate the feasibility of chromosome identification using FISH and to validate the method. It was confirmed that 5S rDNA can be used as a chromosome-specific probe for chromosome identification in E chinensis. The successful application ofFISH in E chinensis shows that chromosome-specific probes can be developed and this finding will facilitate further research on the chromosomes ofpenaeid shrimps.
文摘One of the impediments in the genetic improvement of cotton fiber is the paucity of information about genes associated with fiber development.Availability of chromosome arm substitution line CS-
基金funded by Universidad Pedagogica y Tecnologica de Colombia(Grant No.DIN 14-2017)。
文摘Objective:Chromosomal instability(CIN)is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes,frequently observed in cancer cell populations and is associated with poor prognosis,metastasis,and therapeutic resistance.Breast cancer(BC)is characterized by unstable karyotypes and recent reports have indicated that CIN may influence the response of BC to chemotherapy regimens.However,paradoxical associations between extreme CIN and improved outcome have been observed.Methods:This study aimed to 1)evaluate CIN levels and clonal heterogeneity(CH)in MCF7,ZR-751,MDA-MB468,BT474,and KPL4 BC cells treated with low doses of tamoxifen(TAM),docetaxel(DOC),doxorubicin(DOX),Herceptin(HT),and combined treatments(TAM/DOC,TAM/DOX,TAM/HT,HT/DOC,and HT/DOX)by using fluorescence in situ hybridization(FISH),and 2)examine the association with response to treatments by comparing FISH results with cell proliferation.Results:Intermediate CIN was linked to drug sensitivity according to three characteristics:estrogen receptorα(ERα)and HER2 status,pre-existing CIN level in cancer cells,and the CIN induced by the treatments.ERα+/HER2-cells with intermediate CIN were sensitive to treatment with taxanes(DOC)and anthracyclines(DOX),while ERα-/HER2-,ERα+/HER2+,and ERα-/HER2+cells with intermediate CIN were resistant to these treatments.Conclusions:A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes.
