In multicellular organisms,developmental history of cell divisions and functional annotation of terminal cells can be organized into a cell lineage tree(CLT).The reconstruction of the CLT has long been a major goal in...In multicellular organisms,developmental history of cell divisions and functional annotation of terminal cells can be organized into a cell lineage tree(CLT).The reconstruction of the CLT has long been a major goal in developmental biology and other related fields.Recent technological advancements,especially those in editable genomic barcodes and single-cell high-throughput sequencing,have sparked a new wave of experimental methods for reconstructing CLTs.Here we review the existing experimental approaches to the reconstruction of CLT,which are broadly categorized as either image-based or DNA barcode-based methods.In addition,we present a summary of the related literature based on the biological insight pro-vided by the obtained CLTs.Moreover,we discuss the challenges that will arise as more and better CLT data become available in the near future.Genomic barcoding-based CLT reconstructions and analyses,due to their wide applicability and high scalability,offer the potential for novel biological discoveries,especially those related to general and systemic properties of the developmental process.展开更多
Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model...Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of m RNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by m RNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.展开更多
BACKGROUND Acute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography(ERCP).Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammator...BACKGROUND Acute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography(ERCP).Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammatory drugs(NSAIDs)are more beneficial in preventing post-ERCP pancreatitis(PEP).Randomized controlled trials(RCTs)have also demonstrated the efficacy of glyceryl trinitrate(GTN).We conducted a network meta-analysis to compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.AIM To compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.METHODS A systematic search was done for full-text RCTs of PEP in PubMed,Embase,Science Citation Index,and the Cochrane Controlled Trials database.Inclusion and exclusion criteria were used to screen for eligible RCTs.The major data were extracted by two independent reviewers.The frequentist model was used to conduct this network meta-analysis and obtain the pairwise OR and 95%CI.The data were then extracted and assessed on the basis of the Reference Citation RESULTS Twenty-four eligible RCTs were selected,evaluating seven preventive strategies in 9416 patients.Rectal indomethacin 100 mg plus sublingual GTN(OR:0.21,95%CI:0.09–0.50),rectal diclofenac 100 mg(0.34,0.18–0.65),sublingual GTN(0.34,0.12–0.97),and rectal indomethacin 100 mg(0.49,0.33–0.73)were all more efficacious than placebo in preventing PEP.The combination of rectal indomethacin and sublingual GTN had the highest surface under the cumulative ranking curves(SUCRA)probability of(92.2%)and was the best preventive strategy for moderate-to-severe PEP with a SUCRA probability of(89.2%).CONCLUSION Combination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.展开更多
Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect...Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence.We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found.Using our own and other relevant public data,evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk,indicating evolutionary contingency rather than adaptive convergence.Additionally,tumors from the same MPLC patient are as genetically diverse as those from different patients,while within-tumor genetic heterogeneity is significantly lower.Furthermore,the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor,but not with samples from other tumors or other patients.Overall,there is no evidence of adaptive convergence during the evolution of MPLC.Most importantly,the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient.To fully exploit the strategic value of precision medicine,targeted therapies should be designed and delivered on a per-lesion basis.展开更多
The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems,as in at least one of the sexes,the sex-linked gene dose has been reduced by half.It has been proposed that the transcriptio...The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems,as in at least one of the sexes,the sex-linked gene dose has been reduced by half.It has been proposed that the transcriptional output of the whole X or Z chromosome should be doubled for complete dosage compensation in heterogametic sex.However,owing to the variability of the existing methods to determine the transcriptional differences between sex chromosomes and autosomes(S:A ratios)in different studies,we collected more than 500 public RNA-Seq data set from multiple tissues and species in major clades and proposed a unified computational framework for unbiased and comparable measurement of the S:A ratios of multiple species.We also tested the evolution of dosage compensation more directly by assessing changes in the expression levels of the current sex-linked genes relative to those of the ancestral sex-linked genes.We found that in mammals and birds,the S:A ratio is approximately 0.5,whereas in insects,fishes,and flatworms,the S:A ratio is approximately 1.0.Further analysis showed that the fraction of dosage-sensitive housekeeping genes on the X/Z chromosome is significantly correlated with the S:A ratio.In addition,the degree of degeneration of the Y chromosome may be responsible for the change in the S:A ratio in mammals without a dosage compensation mechanism.Our observations offer unequivocal support for the sex chromosome insensitivity hypothesis in animals and suggest that dosage sensitivity states of sex chromosomes are a major factor underlying different evolutionary strategies of dosage compensation.展开更多
Understanding how gene expression is translated to phenotype is central to modern molecular biology,and the success is contingent on the intrinsic tractability of the specific traits under examination.However, an a pr...Understanding how gene expression is translated to phenotype is central to modern molecular biology,and the success is contingent on the intrinsic tractability of the specific traits under examination.However, an a priori estimate of trait tractability from the perspective of gene expression is unavailable.Motivated by the concept of entropy in a thermodynamic system, we here propose such an estimate(S_T)by gauging the number(N) of expression states that underlie the same trait abnormality, with large S_T corresponding to large N. By analyzing over 200 yeast morphological traits, we show that S_T predicts the tractability of an expression-trait relationship. We further show that S_T is ultimately determined by natural selection, which builds co-regulated gene modules to minimize possible expression states.展开更多
The famous Kadomtsev-Petviashvili(KP)equation 1 s a classical equation In soliton tneory.A Backlund transformation between the KP equation and the Schwarzian KP equation is demonstrated by means of the truncated Painl...The famous Kadomtsev-Petviashvili(KP)equation 1 s a classical equation In soliton tneory.A Backlund transformation between the KP equation and the Schwarzian KP equation is demonstrated by means of the truncated Painlev6 expansion in this paper.One-parameter group transformations and one-parameter subgroup-invariant solutions for the extended KP equation are obtained.The consistent Riccati expansion(CRE) solvability of the KP equation is proved.Some interaction structures between soliton-cnoidal waves are obtained by CRE and several evolution graphs and density graphs are plotted.展开更多
We study a forced variable-coefficient extended Korteweg-de Vries(KdV)equation in fluid dynamics with respect to internal solitary wave.Bäcklund transformations of the forced variable-coefficient extended KdV equ...We study a forced variable-coefficient extended Korteweg-de Vries(KdV)equation in fluid dynamics with respect to internal solitary wave.Bäcklund transformations of the forced variable-coefficient extended KdV equation are demonstrated with the help of truncated Painlevéexpansion.When the variable coefficients are time-periodic,the wave function evolves periodically over time.Symmetry calculation shows that the forced variable-coefficient extended KdV equation is invariant under the Galilean transformations and the scaling transformations.One-parameter group transformations and one-parameter subgroup invariant solutions are presented.Cnoidal wave solutions and solitary wave solutions of the forced variable-coefficient extended KdV equation are obtained by means of function expansion method.The consistent Riccati expansion(CRE)solvability of the forced variable-coefficient extended KdV equation is proved by means of CRE.Interaction phenomenon between cnoidal waves and solitary waves can be observed.Besides,the interaction waveform changes with the parameters.When the variable parameters are functions of time,the interaction waveform will be not regular and smooth.展开更多
In order to study the characteristics of dust acoustic waves in a uniform dense dusty magnetoplasma system, a nonlinear dynamical equation is deduced using the quantum hydrodynamic model to account for dust–neutral c...In order to study the characteristics of dust acoustic waves in a uniform dense dusty magnetoplasma system, a nonlinear dynamical equation is deduced using the quantum hydrodynamic model to account for dust–neutral collisions. The linear dispersion relation indicates that the scale lengths of the system are revised by the quantum parameter, and that the wave motion decays gradually leading the system to a stable state eventually. The variations of the dispersion frequency with the dust concentration, collision frequency, and magnetic field strength are discussed. For the coherent nonlinear dust acoustic waves, new analytic solutions are obtained, and it is found that big shock waves and wide explosive waves may be easily produced in the background of high dusty density, strong magnetic field, and weak collision. The relevance of the obtained results is referred to dense dusty astrophysical circumstances.展开更多
The secondary structure is a fundamental feature of both non-coding RNAs(ncRNAs)and messenger RNAs(mRNAs).However,our understanding of the secondary structures of mRNAs,especially those of the coding regions,remains e...The secondary structure is a fundamental feature of both non-coding RNAs(ncRNAs)and messenger RNAs(mRNAs).However,our understanding of the secondary structures of mRNAs,especially those of the coding regions,remains elusive,likely due to translation and the lack of RNA-binding proteins that sustain the consensus structure like those binding to ncRNAs.Indeed,mRNAs have recently been found to adopt diverse alternative structures,but the overall functional significance remains untested.We hereby approach this problem by estimating the folding specificity,i.e.,the probability that a fragment of an mRNA folds back to the same partner once refolded.We show that the folding specificity of mRNAs is lower than that of ncRNAs and exhibits moderate evolutionary conservation.Notably,we find that specific rather than alternative folding is likely evolutionarily adaptive since specific folding is frequently associated with functionally important genes or sites within a gene.Additional analysis in combination with ribosome density suggests the ability to modulate ribosome movement as one potential functional advantage provided by specific folding.Our findings reveal a novel facet of the RNA structurome with important functional and evolutionary implications and indicate a potential method for distinguishing the mRNA secondary structures maintained by natural selection from molecular noise.展开更多
基金supported by the National Key Research and Development Program of China(2021YFF1200904,2021YFA1302500 to J.-R.Y.)the National Natural Science Foundation of China(32122022,31871320 to J.-R.Y.)by Science and Technology Planning Project of Guangdong Province,China(2014A030304053 to X.Z.).
文摘In multicellular organisms,developmental history of cell divisions and functional annotation of terminal cells can be organized into a cell lineage tree(CLT).The reconstruction of the CLT has long been a major goal in developmental biology and other related fields.Recent technological advancements,especially those in editable genomic barcodes and single-cell high-throughput sequencing,have sparked a new wave of experimental methods for reconstructing CLTs.Here we review the existing experimental approaches to the reconstruction of CLT,which are broadly categorized as either image-based or DNA barcode-based methods.In addition,we present a summary of the related literature based on the biological insight pro-vided by the obtained CLTs.Moreover,we discuss the challenges that will arise as more and better CLT data become available in the near future.Genomic barcoding-based CLT reconstructions and analyses,due to their wide applicability and high scalability,offer the potential for novel biological discoveries,especially those related to general and systemic properties of the developmental process.
基金supported by the start-up grant from“Top 100 Talents Program”of Sun Yat-sen University to JRY(50000-31131114)General Program of National Natural Science Foundation of China to JRY(31671320)
文摘Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of m RNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by m RNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.
文摘BACKGROUND Acute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography(ERCP).Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammatory drugs(NSAIDs)are more beneficial in preventing post-ERCP pancreatitis(PEP).Randomized controlled trials(RCTs)have also demonstrated the efficacy of glyceryl trinitrate(GTN).We conducted a network meta-analysis to compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.AIM To compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.METHODS A systematic search was done for full-text RCTs of PEP in PubMed,Embase,Science Citation Index,and the Cochrane Controlled Trials database.Inclusion and exclusion criteria were used to screen for eligible RCTs.The major data were extracted by two independent reviewers.The frequentist model was used to conduct this network meta-analysis and obtain the pairwise OR and 95%CI.The data were then extracted and assessed on the basis of the Reference Citation RESULTS Twenty-four eligible RCTs were selected,evaluating seven preventive strategies in 9416 patients.Rectal indomethacin 100 mg plus sublingual GTN(OR:0.21,95%CI:0.09–0.50),rectal diclofenac 100 mg(0.34,0.18–0.65),sublingual GTN(0.34,0.12–0.97),and rectal indomethacin 100 mg(0.49,0.33–0.73)were all more efficacious than placebo in preventing PEP.The combination of rectal indomethacin and sublingual GTN had the highest surface under the cumulative ranking curves(SUCRA)probability of(92.2%)and was the best preventive strategy for moderate-to-severe PEP with a SUCRA probability of(89.2%).CONCLUSION Combination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.
基金supported by the National Key Research and Development Program of China to J.-R. Y.(2021YFF1200904 and2021YFA1302500)the National Natural Science Foundation of China to J.-R. Y.(31871320 and 81830103)+1 种基金by Science and Technology Planning Project of ZhuHai,China to H. C.by Science and Technology Planning Project of Guangdong Province,China to X. Z.(2014A030304053)
文摘Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence.We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found.Using our own and other relevant public data,evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk,indicating evolutionary contingency rather than adaptive convergence.Additionally,tumors from the same MPLC patient are as genetically diverse as those from different patients,while within-tumor genetic heterogeneity is significantly lower.Furthermore,the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor,but not with samples from other tumors or other patients.Overall,there is no evidence of adaptive convergence during the evolution of MPLC.Most importantly,the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient.To fully exploit the strategic value of precision medicine,targeted therapies should be designed and delivered on a per-lesion basis.
基金supported by grants from the National Key R&D Program of China(2017YFA0103504 to X.C.and project number:2018ZX10301402 awarded to J.-R.Y.)the National Natural Science Foundation of China(project numbers:31771406 awarded to X.C.and 31671320,31871320,and 81830103 awarded to J.-R.Y.)
文摘The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems,as in at least one of the sexes,the sex-linked gene dose has been reduced by half.It has been proposed that the transcriptional output of the whole X or Z chromosome should be doubled for complete dosage compensation in heterogametic sex.However,owing to the variability of the existing methods to determine the transcriptional differences between sex chromosomes and autosomes(S:A ratios)in different studies,we collected more than 500 public RNA-Seq data set from multiple tissues and species in major clades and proposed a unified computational framework for unbiased and comparable measurement of the S:A ratios of multiple species.We also tested the evolution of dosage compensation more directly by assessing changes in the expression levels of the current sex-linked genes relative to those of the ancestral sex-linked genes.We found that in mammals and birds,the S:A ratio is approximately 0.5,whereas in insects,fishes,and flatworms,the S:A ratio is approximately 1.0.Further analysis showed that the fraction of dosage-sensitive housekeeping genes on the X/Z chromosome is significantly correlated with the S:A ratio.In addition,the degree of degeneration of the Y chromosome may be responsible for the change in the S:A ratio in mammals without a dosage compensation mechanism.Our observations offer unequivocal support for the sex chromosome insensitivity hypothesis in animals and suggest that dosage sensitivity states of sex chromosomes are a major factor underlying different evolutionary strategies of dosage compensation.
基金supported by research grants from National Natural Science Foundation of China (Nos. 31630042 and 91731302)
文摘Understanding how gene expression is translated to phenotype is central to modern molecular biology,and the success is contingent on the intrinsic tractability of the specific traits under examination.However, an a priori estimate of trait tractability from the perspective of gene expression is unavailable.Motivated by the concept of entropy in a thermodynamic system, we here propose such an estimate(S_T)by gauging the number(N) of expression states that underlie the same trait abnormality, with large S_T corresponding to large N. By analyzing over 200 yeast morphological traits, we show that S_T predicts the tractability of an expression-trait relationship. We further show that S_T is ultimately determined by natural selection, which builds co-regulated gene modules to minimize possible expression states.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11775047,11775146,and 11865013)the Science and Technology Project Foundation of Zhongshan City,China(Grant No.2017B1016).
文摘The famous Kadomtsev-Petviashvili(KP)equation 1 s a classical equation In soliton tneory.A Backlund transformation between the KP equation and the Schwarzian KP equation is demonstrated by means of the truncated Painlev6 expansion in this paper.One-parameter group transformations and one-parameter subgroup-invariant solutions for the extended KP equation are obtained.The consistent Riccati expansion(CRE) solvability of the KP equation is proved.Some interaction structures between soliton-cnoidal waves are obtained by CRE and several evolution graphs and density graphs are plotted.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11775047,11775146,and 11865013).
文摘We study a forced variable-coefficient extended Korteweg-de Vries(KdV)equation in fluid dynamics with respect to internal solitary wave.Bäcklund transformations of the forced variable-coefficient extended KdV equation are demonstrated with the help of truncated Painlevéexpansion.When the variable coefficients are time-periodic,the wave function evolves periodically over time.Symmetry calculation shows that the forced variable-coefficient extended KdV equation is invariant under the Galilean transformations and the scaling transformations.One-parameter group transformations and one-parameter subgroup invariant solutions are presented.Cnoidal wave solutions and solitary wave solutions of the forced variable-coefficient extended KdV equation are obtained by means of function expansion method.The consistent Riccati expansion(CRE)solvability of the forced variable-coefficient extended KdV equation is proved by means of CRE.Interaction phenomenon between cnoidal waves and solitary waves can be observed.Besides,the interaction waveform changes with the parameters.When the variable parameters are functions of time,the interaction waveform will be not regular and smooth.
基金supported by the National Natural Science Foundation of China(Grant Nos.11365017,11465015,11305031,11405110,and 11275123)the Technology Landing Project of the Education Department of Jiangxi Province of China(Grant No.KJLD13086)
文摘In order to study the characteristics of dust acoustic waves in a uniform dense dusty magnetoplasma system, a nonlinear dynamical equation is deduced using the quantum hydrodynamic model to account for dust–neutral collisions. The linear dispersion relation indicates that the scale lengths of the system are revised by the quantum parameter, and that the wave motion decays gradually leading the system to a stable state eventually. The variations of the dispersion frequency with the dust concentration, collision frequency, and magnetic field strength are discussed. For the coherent nonlinear dust acoustic waves, new analytic solutions are obtained, and it is found that big shock waves and wide explosive waves may be easily produced in the background of high dusty density, strong magnetic field, and weak collision. The relevance of the obtained results is referred to dense dusty astrophysical circumstances.
基金supported by the National Key Technology R&D Program of China(Grant Nos.2017YFA0103504 to XC,2018ZX10301402 to JRY)the National Natural Science Foundation of China(Grant Nos.31671320,31871320,and 81830103 to JRY)the start-up grants from the“100 Top Talents Program”of Sun Yat-sen University,China(Grant Nos.50000-18821112 to XC,50000-18821117 to JRY).
文摘The secondary structure is a fundamental feature of both non-coding RNAs(ncRNAs)and messenger RNAs(mRNAs).However,our understanding of the secondary structures of mRNAs,especially those of the coding regions,remains elusive,likely due to translation and the lack of RNA-binding proteins that sustain the consensus structure like those binding to ncRNAs.Indeed,mRNAs have recently been found to adopt diverse alternative structures,but the overall functional significance remains untested.We hereby approach this problem by estimating the folding specificity,i.e.,the probability that a fragment of an mRNA folds back to the same partner once refolded.We show that the folding specificity of mRNAs is lower than that of ncRNAs and exhibits moderate evolutionary conservation.Notably,we find that specific rather than alternative folding is likely evolutionarily adaptive since specific folding is frequently associated with functionally important genes or sites within a gene.Additional analysis in combination with ribosome density suggests the ability to modulate ribosome movement as one potential functional advantage provided by specific folding.Our findings reveal a novel facet of the RNA structurome with important functional and evolutionary implications and indicate a potential method for distinguishing the mRNA secondary structures maintained by natural selection from molecular noise.
