On the basis of information theory and statistical methods, we use mutual information, n- tuple entropy and conditional entropy, combined with biological characteristics, to analyze the long range correlation and shor...On the basis of information theory and statistical methods, we use mutual information, n- tuple entropy and conditional entropy, combined with biological characteristics, to analyze the long range correlation and short range correlation in human Y chromosome palindromes. The magnitude distribution of the long range correlation which can be reflected by the mutual information is PS〉PSa〉PSb （P5a and P5b are the sequences that replace solely Alu repeats and all interspersed repeats with random uneorrelated sequences in human Y chromosome palindrome 5, respectively）; and the magnitude distribution of the short range correlation which can be reflected by the n-tuple entropy and the conditional entropy is PS〉P5a〉PSb〉random uncorrelated sequence. In other words, when the Alu repeats and all interspersed repeats replace with random uneorrelated sequence, the long range and short range correlation decrease gradually. However, the random nncorrelated sequence has no correlation. This research indicates that more repeat sequences result in stronger correlation between bases in human Y chromosome. The analyses may be helpful to understand the special structures of human Y chromosome palindromes profoundly.展开更多
Palindrome number conjecture: Take any non-palindromic natural number with two or more digits, add its inverse ordinal number, continue to use the inverted number of sum plus sum, repeat this process continuously. Aft...Palindrome number conjecture: Take any non-palindromic natural number with two or more digits, add its inverse ordinal number, continue to use the inverted number of sum plus sum, repeat this process continuously. After a finite number of operations, a palindrome number must be obtained. We firstly give out several definitions: The pure-single-digit-of-sum is the number of single digits that only count the sum of two numbers of the same digit in the vertical operation of addition, which is referred to as pure single digit for short, denoted by g. The pure-carry-digit-of-sum is the carry digit that only counts the sum of two numbers in the same bit in the vertical operation of addition. It is a special number composed of only 1 and 0, which is represented by j'. The complement-0-carry-digit-of-sum is to supplement a 0 on the last side of j' according to the rule of adding bits, which is denoted by j. Therefore, in the addition operation, the sum of any natural number and its inverse ordinal number is divided into two parts: g and j. Then, the characteristics of g and j are characterized by the following two theorems: Theorem 1: As all the numbers in j are 0, j is the palindrome number;As the numbers in j are not all 0, j is not a palindrome number. Theorem 2: The sum of any palindrome number H and any non-palindrome j number must be a non-palindrome number. Then we proved the palindrome number conjecture is not correct by using the above two theorems.展开更多
We analyze for the first time the rules of breaking in an X-palindrome between human and chimpanzee. Results indicate that although the overall changes that occurred in the human X-palindrome are fewer than in the chi...We analyze for the first time the rules of breaking in an X-palindrome between human and chimpanzee. Results indicate that although the overall changes that occurred in the human X-palindrome are fewer than in the chimpanzee, mutations occurring between the left arm and right arm were nearly equivalent both in human and chimpanzee when compared with orangutan, which implies evolutionary synchronization. However, there are many more A/T→G/C changes than G/C→A/T in a single arm, which would lead to an increasing trend in GC content and suggest that the composition is not at equilibrium. In addition, it is remarkable to find that there are much more asymmetrical nucleotide changes between the two arms of the human palindrome than that of the chimpanzee palindrome, and these mutations are prone to occur between bases with similar chemical structures. The symmetry seems higher in the chimpanzee palindrome than in the human X-palindrome.展开更多
The palindrome is one class of symmetrical duplications with reverse complementary characters, which is widely distributed in many organisms. Graphical representation of DNA sequence provides a simple way of viewing a...The palindrome is one class of symmetrical duplications with reverse complementary characters, which is widely distributed in many organisms. Graphical representation of DNA sequence provides a simple way of viewing and comparing various genomic structures. Through 3-D DNA walk analysis, the similarity and differences in nucleotide composition, as well as the evolutionary relationship between human and chimpanzee MAGE]CSAG-palindromes, can be clearly revealed. Further wavelet analysis indicated that duplicated segments have irregular patterns compared to their surrounding sequences. However, sequence similarity analysis suggests that there is possible common ancestor between human and chimpanzee MAGE]CSAG-palindromes. Based on the specific distribution and orien- tation of the repeated sequences, a simple possible evolutionary model of the palindromes is suggested, which may help us to better understand the evolutionary course of the genes and the symmetrical sequences.展开更多
BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on th...BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.展开更多
A recent study by Qin et al emphasized the potential of zinc finger protein 71(ZNF71)as a promising biomarker for hepatocellular carcinoma(HCC).The authors offered valuable insights into the relationship between ZNF71...A recent study by Qin et al emphasized the potential of zinc finger protein 71(ZNF71)as a promising biomarker for hepatocellular carcinoma(HCC).The authors offered valuable insights into the relationship between ZNF71 and various clinical and pathological stages of HCC.However,several limitations are required to be addressed to improve the findings.These limitations include concerns regarding patient selection,the generalizability of the results,and the necessity for functional validation to establish ZNF71’s specific role in the progression of HCC.Furthermore,statistical issues related to multiple comparisons,confounding variables,and the inherent heterogeneity of high-throughput datasets warrant careful consideration.Future research should focus on multi-institutional cohorts,utilize in vivo models,and compare ZNF71 with established biomarkers to strengthen the clinical relevance of ZNF71.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2...BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2F transcription factor 1(E2F1)-mediated transcriptional activation.This study integrates multiomics and clustered regularly interspaced short palindromic repeats(CRISPR)screening to delineate RAC3’s roles.RAC3 overexpression correlates with advanced HCC and patient age,while its knockout suppresses proliferation.Mechanistically,RAC3 dysregulates cell-cycle checkpoints through E2F1 binding.Pharmacological RAC3 inhibition disrupts tumor growth and synergizes with chemotherapy to overcome resistance.AIM To explore RAC3’s expression,clinical links,and HCC mechanisms via multiomics and functional genomics.METHODS Multiomic integration of The Cancer Genome Atlas(TCGA),Gene Expression Omnibus,and Genotype-Tissue Expression datasets was performed to analyze RAC3 mRNA expression.Immunohistochemistry quantified RAC3 protein in 108 HCC/adjacent tissue pairs.Kaplan–Meier/Cox regression assessed prognostic significance using TCGA data.CRISPR screening validated RAC3’s necessity for HCC proliferation.Functional enrichment identified associated pathways;hTFtarget/JASPAR predicted transcription factors,validated via chromatin immunoprecipitation sequencing(ChIP-seq).RESULTS RAC3 exhibited significant mRNA and protein overexpression in HCC tissues,which was correlated with advanced tumor stages and reduced overall survival rates(hazard ratio=1.82,95%CI:1.31–2.53).Genetic ablation of RAC3 suppressed HCC cell proliferation across 16 cell lines.Pathway analysis revealed RAC3’s predominant involvement in cell-cycle regulation,DNA replication,and nucleocytoplasmic transport.Mechanistic investigations identified E2F1 as a pivotal upstream transcriptional regulator,and ChIP-seq analysis validated its direct binding to the RAC3 promoter region.These findings suggest that RAC3 drives HCC progression through E2F1-mediated cell-cycle dysregulation.CONCLUSION This study identified RAC3 as a key HCC oncogenic driver;its overexpression links to poor prognosis/resistance.Targeting the RAC3/E2F1 axis offers a new therapy,which highlights RAC3 as a biomarker/target.展开更多
BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in pa...BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.展开更多
基金This work was supported by the National Natu- ral Science Foundation of China （No.20173023 and No.90203012） and the Specialized Research Fund for the Doctoral Program of Higher Education of China （No.20020730006）.
文摘On the basis of information theory and statistical methods, we use mutual information, n- tuple entropy and conditional entropy, combined with biological characteristics, to analyze the long range correlation and short range correlation in human Y chromosome palindromes. The magnitude distribution of the long range correlation which can be reflected by the mutual information is PS〉PSa〉PSb （P5a and P5b are the sequences that replace solely Alu repeats and all interspersed repeats with random uneorrelated sequences in human Y chromosome palindrome 5, respectively）; and the magnitude distribution of the short range correlation which can be reflected by the n-tuple entropy and the conditional entropy is PS〉P5a〉PSb〉random uncorrelated sequence. In other words, when the Alu repeats and all interspersed repeats replace with random uneorrelated sequence, the long range and short range correlation decrease gradually. However, the random nncorrelated sequence has no correlation. This research indicates that more repeat sequences result in stronger correlation between bases in human Y chromosome. The analyses may be helpful to understand the special structures of human Y chromosome palindromes profoundly.
文摘Palindrome number conjecture: Take any non-palindromic natural number with two or more digits, add its inverse ordinal number, continue to use the inverted number of sum plus sum, repeat this process continuously. After a finite number of operations, a palindrome number must be obtained. We firstly give out several definitions: The pure-single-digit-of-sum is the number of single digits that only count the sum of two numbers of the same digit in the vertical operation of addition, which is referred to as pure single digit for short, denoted by g. The pure-carry-digit-of-sum is the carry digit that only counts the sum of two numbers in the same bit in the vertical operation of addition. It is a special number composed of only 1 and 0, which is represented by j'. The complement-0-carry-digit-of-sum is to supplement a 0 on the last side of j' according to the rule of adding bits, which is denoted by j. Therefore, in the addition operation, the sum of any natural number and its inverse ordinal number is divided into two parts: g and j. Then, the characteristics of g and j are characterized by the following two theorems: Theorem 1: As all the numbers in j are 0, j is the palindrome number;As the numbers in j are not all 0, j is not a palindrome number. Theorem 2: The sum of any palindrome number H and any non-palindrome j number must be a non-palindrome number. Then we proved the palindrome number conjecture is not correct by using the above two theorems.
基金ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China （No.20173023 and No.90203012） and the Specialized Research Fund for the Doctoral Program of Higher Education of China （No.20020730006）.
文摘We analyze for the first time the rules of breaking in an X-palindrome between human and chimpanzee. Results indicate that although the overall changes that occurred in the human X-palindrome are fewer than in the chimpanzee, mutations occurring between the left arm and right arm were nearly equivalent both in human and chimpanzee when compared with orangutan, which implies evolutionary synchronization. However, there are many more A/T→G/C changes than G/C→A/T in a single arm, which would lead to an increasing trend in GC content and suggest that the composition is not at equilibrium. In addition, it is remarkable to find that there are much more asymmetrical nucleotide changes between the two arms of the human palindrome than that of the chimpanzee palindrome, and these mutations are prone to occur between bases with similar chemical structures. The symmetry seems higher in the chimpanzee palindrome than in the human X-palindrome.
基金supported by the Fundamental Research Funds for the Central Universities(Program No.zyz2012063)
文摘The palindrome is one class of symmetrical duplications with reverse complementary characters, which is widely distributed in many organisms. Graphical representation of DNA sequence provides a simple way of viewing and comparing various genomic structures. Through 3-D DNA walk analysis, the similarity and differences in nucleotide composition, as well as the evolutionary relationship between human and chimpanzee MAGE]CSAG-palindromes, can be clearly revealed. Further wavelet analysis indicated that duplicated segments have irregular patterns compared to their surrounding sequences. However, sequence similarity analysis suggests that there is possible common ancestor between human and chimpanzee MAGE]CSAG-palindromes. Based on the specific distribution and orien- tation of the repeated sequences, a simple possible evolutionary model of the palindromes is suggested, which may help us to better understand the evolutionary course of the genes and the symmetrical sequences.
基金Supported by National Natural Science Foundation of China,No.82160762Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project,No.GXZYA20230267+2 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598060XChina Undergraduate Innovation and Entrepreneurship Training Program,No.X202410598360Future Academic Star of Guangxi Medical University,No.WLXSZX24074.
文摘BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.
文摘A recent study by Qin et al emphasized the potential of zinc finger protein 71(ZNF71)as a promising biomarker for hepatocellular carcinoma(HCC).The authors offered valuable insights into the relationship between ZNF71 and various clinical and pathological stages of HCC.However,several limitations are required to be addressed to improve the findings.These limitations include concerns regarding patient selection,the generalizability of the results,and the necessity for functional validation to establish ZNF71’s specific role in the progression of HCC.Furthermore,statistical issues related to multiple comparisons,confounding variables,and the inherent heterogeneity of high-throughput datasets warrant careful consideration.Future research should focus on multi-institutional cohorts,utilize in vivo models,and compare ZNF71 with established biomarkers to strengthen the clinical relevance of ZNF71.
基金Supported by National Natural Science Foundation of China,No.82260581.
文摘BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2F transcription factor 1(E2F1)-mediated transcriptional activation.This study integrates multiomics and clustered regularly interspaced short palindromic repeats(CRISPR)screening to delineate RAC3’s roles.RAC3 overexpression correlates with advanced HCC and patient age,while its knockout suppresses proliferation.Mechanistically,RAC3 dysregulates cell-cycle checkpoints through E2F1 binding.Pharmacological RAC3 inhibition disrupts tumor growth and synergizes with chemotherapy to overcome resistance.AIM To explore RAC3’s expression,clinical links,and HCC mechanisms via multiomics and functional genomics.METHODS Multiomic integration of The Cancer Genome Atlas(TCGA),Gene Expression Omnibus,and Genotype-Tissue Expression datasets was performed to analyze RAC3 mRNA expression.Immunohistochemistry quantified RAC3 protein in 108 HCC/adjacent tissue pairs.Kaplan–Meier/Cox regression assessed prognostic significance using TCGA data.CRISPR screening validated RAC3’s necessity for HCC proliferation.Functional enrichment identified associated pathways;hTFtarget/JASPAR predicted transcription factors,validated via chromatin immunoprecipitation sequencing(ChIP-seq).RESULTS RAC3 exhibited significant mRNA and protein overexpression in HCC tissues,which was correlated with advanced tumor stages and reduced overall survival rates(hazard ratio=1.82,95%CI:1.31–2.53).Genetic ablation of RAC3 suppressed HCC cell proliferation across 16 cell lines.Pathway analysis revealed RAC3’s predominant involvement in cell-cycle regulation,DNA replication,and nucleocytoplasmic transport.Mechanistic investigations identified E2F1 as a pivotal upstream transcriptional regulator,and ChIP-seq analysis validated its direct binding to the RAC3 promoter region.These findings suggest that RAC3 drives HCC progression through E2F1-mediated cell-cycle dysregulation.CONCLUSION This study identified RAC3 as a key HCC oncogenic driver;its overexpression links to poor prognosis/resistance.Targeting the RAC3/E2F1 axis offers a new therapy,which highlights RAC3 as a biomarker/target.
基金Supported by Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220521Guangxi Higher Education Undergraduate Teaching Reform Project,No.2022JGA147The National College Students’Innovation and Entrepreneurship Training Program,No.202310598042.
文摘BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.
