The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to b...The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.展开更多
Several tritylodontid taxa have been reported from the Upper Jurassic of the Wucaiwan area in the Junggar Basin of Xinjiang,northwestern China,including Yuanotherium minor.The original study described the partially pr...Several tritylodontid taxa have been reported from the Upper Jurassic of the Wucaiwan area in the Junggar Basin of Xinjiang,northwestern China,including Yuanotherium minor.The original study described the partially preserved postcanine teeth in the middle of the left upper maxilla.After detailed re-examination of the specimen and by CT scanning,3D reconstruction,and scanning electron microscopy observations,we provided a more detailed description of the osteology,neurosensory,and tooth wear pattern for all the bones preserved in this specimen and clarified some characters.Based on new information about the cusp wear pattern,the chewing movement pattern of the dentition and detailed cusp morphology,we discussed the cuspal homology of upper cheek teeth of tritylodontids and postulate a standardized method for cusp identification.We hypothesize that the unique maxilla characteristics furnish the evidence for transitional stages about the evolution of the upper jaw-palate structure in tritylodontids.展开更多
Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,poly...Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,polyphenols,and flavonoids that contribute to its antimicrobial,antioxidant,and immuno-modulatory properties.Additionally,honey is effective in managing some conditions,such as antibiotic-resistant infections,inflammation,and oxidative stress-related diseases.This review explores the extensive health benefits of honey,emphasizing the homology between food and medicine,as proposed by TCM philosophy.Further,this review explores the traditional applications of honey in respiratory health,wound healing,and gastrointestinal support,along with modern scientific validation of these uses.Moreover,the role of honey as a dietary supplement,functional food,and preservative in culinary practices is examined.Overall,this review highlights the synergy between ancient wisdom and contemporary science,advocating for the continued exploration of the role of honey in health,nutrition,and medicine.展开更多
Chronic heart failure(CHF)is a pathological state in which the cardiac ejection fraction is insufficient to meet an individual's metabolic needs owing to changes in the cardiac structure or function.Various etiolo...Chronic heart failure(CHF)is a pathological state in which the cardiac ejection fraction is insufficient to meet an individual's metabolic needs owing to changes in the cardiac structure or function.Various etiologies such as myocardial infarction and inflammation are implicated,and the main symptoms are dyspnea,lower limb edema,fatigue,and discomfort during rest or exercise.CHF is the primary outcome of cardiovascular disease,and the increasing morbidity and mortality rates highlight the significant risks of this condition.According to traditional Chinese medicine,the pathogenesis of CHF is deficiency of heart qi and heart yang,which predominantly affects the heart,but may also impede the function of other zang-organs such as the spleen and kidney,and aggravate the symptoms of heart failure.With technological advancements and enhanced awareness of health conditions and disease prevention,China has promoted traditional medicine practices such as medicine and food homology(MFH),which has received increasing attention in recent years.This concept stipulates that certain medicines and foods have the same origin;ergo,these foods have medicinal properties,with many being used in the pre-vention and treatment of CHF.However,the efficacy and safety of MHF substances have yet to be determined,and there is no consensus regarding the development of disease prevention and treatment strategies.This article therefore reviews the current evidence for MFH in the prevention and treatment of CHF by summarizing the therapeutic potential of this practice and discussing treatment strategies and aims to improve the understanding of Chinese medicine and food homologous substances in the treatment of this condition,as well as highlight the current literature and avenues for future research.展开更多
pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical p...pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical properties, hydrophilicity/hydrophobicity, signal peptide, secondary structure, coiled coil, transmembrane domains, O-glycogylation site, active site, subcellular localization, functional structural domains and three-dimensional structure were analyzed by a series of bioinformatics software. The results showed that mPDI was a hydrophobic and stable protein with 3 coiled coils, 30-glycogylation sites, 2 structural domains of thioredoxin, 2 active sites of thioredoxin, and located in rough endoplasmic reticulum. It has 512 amino acids, the theoretical pl is 4.98, and signal peptide located in 1-24AA. In the secondary structure, a-helix, random coil, extended chain is 26.37%, 53.32%, 20.31% respectively. The validation of modeling accords with the stereochemistry.展开更多
Rice metallothionein-like protein (rgMT) shows characteristics of a three-section pattern composed of two highly conserved cysteine rich (CR) domains in the terminals and a spacer without cysteine (cys) residues in th...Rice metallothionein-like protein (rgMT) shows characteristics of a three-section pattern composed of two highly conserved cysteine rich (CR) domains in the terminals and a spacer without cysteine (cys) residues in the center of the molecule. In this paper, the two CR domains and the spacer region were modeled by the distance geometry and homology methods separately. For the CR domains, twenty random models were generated for each cys combination based on the constraint conditions of CXC (C represents cys, X represents any amino acid other than cys), and CXXC motifs and a metal-sulfur chelating cluster. Four models for the N-terminal and two for C-terminal CR domain containing metal chelating structures formed by different combinations of cys were selected from 900 possible conformations. The GOR method was used to predict the secondary structure of the spacer region and its model was built by the homology method. After three parts of the protein were modeled, they were connected to form a three-dimensional structure model of rgMT. The whole conformation showed that rgMT could form two independent metal-sulfur chelating structures connected by a spacer peptide, without a structural or energy barrier for them to form two independent metal-chelating clusters just as mammalian metallothionein (MT) proteins. As all plant metallothionein-like (MT-L) proteins have the same primary structural characteristic, two CR domains connected by a spacer region, and many have the same cys arrangement pattern as rgMT, the three-dimensional structure model of rgMT will provide an important reference for the structural study of other plant MT-L proteins.展开更多
Let A be a tame Hecke algebra of type A. A new minimal projective bimodule resolution for A is constructed and the dimensions of all the Hochschild homology groups and cyclic homology groups are calculated explicitly.
In this paper, we propose a new algorithm to compute the homology of a finitely generated chain complex. Our method is based on grouping several reductions into structures that can be encoded as directed acyclic graph...In this paper, we propose a new algorithm to compute the homology of a finitely generated chain complex. Our method is based on grouping several reductions into structures that can be encoded as directed acyclic graphs. The organized reduction pairs lead to sequences of projection maps that reduce the number of generators while preserving the homology groups of the original chain complex. This sequencing of reduction pairs allows updating the boundary information in a single step for a whole set of reductions, which shows impressive gains in computational performance compared to existing methods. In addition, our method gives the homology generators for a small additional cost.展开更多
Breakthroughs in the generation of programmable sequence-specific nucleases (SSNs), such as zinc finger nucleases (ZFNs),TAL effector nucleases (TALENs) and the RNA-directed nuclease CRISPR-associated protein 9 (Cas9)...Breakthroughs in the generation of programmable sequence-specific nucleases (SSNs), such as zinc finger nucleases (ZFNs),TAL effector nucleases (TALENs) and the RNA-directed nuclease CRISPR-associated protein 9 (Cas9), have greatly increased the ease of plant genome engineering (Voytas, 2013; Malzahn et al.,2017). Programmable SSNs introduce a DNA double-strand break展开更多
Detecting remote homology proteins is a challenging problem for both basic research and drug development. Although there are a couple of methods to deal with this problem, the benchmark datasets based on which the exi...Detecting remote homology proteins is a challenging problem for both basic research and drug development. Although there are a couple of methods to deal with this problem, the benchmark datasets based on which the existing methods were trained and tested contain many high homologous samples as reflected by the fact that the cutoff threshold was set at 95%. In this study, we reconstructed the benchmark dataset by setting the threshold at 40%, meaning none of the proteins included in the benchmark dataset has more than 40% pairwise sequence identity with any other in the same subset. Using the new benchmark dataset, we proposed a new predictor called “dRHP-GreyFun” based on the grey modeling and functional domain approach. Rigorous cross-validations have indicated that the new predictor is superior to its counterparts in both enhancing success rates and reducing computational cost. The predictor can be downloaded from https://github.com/jcilwz/dRHP-GreyFun.展开更多
<abstract>Aim: Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the ra...<abstract>Aim: Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the rat. Methods: 'Electronic screening' of Expressed Sequence Tag (EST) and genomic databases, followed by RT-PCR and Northern blot analysis. Results: Rodent ESTs and genomic sequences homologous to HE3, HE4 and Ce8/Ly6G5C were identified in the public databases and the 'full-length' rat cDNAs cloned. To emphasise their homology to the human and canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat counterparts, respectively. mRNA expression patterns were analysed in rats, including rat HEl and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were only found in the rat epididymis, while Re4 showed a broader tissue distribution. Within the epididymis, Re3 and Re4 mRNAs were detected in all regions; Re8, on the other hand, was restricted to the caput. During postnatal development, Re3 and control mRNAs were found from the earliest stages investigated, while Re8 mRNA was observed only from day 24 postnatum, corresponding to the onset of spermatogenesis in the prepubertal testis. Castration and testosterone supplementation of adult male rats suggested that none of the cloned mRNAs was directly androgen-regulated. Efferent duct ligation, however, showed that Re8 mRNA levels depended on testicular factors other than androgens. Conclusion: The novel rodent cDNAs can now be used to monitor epididymal gene expression more closely and to set up various regulatory and functional studies.展开更多
Abstract Objective To investigate the theoretical model of the three-dimensional structure of mosquitocida Cry3OCa2 and its molecular docking with N-acetylgalactosamine. Methods The theoretical model of Cry30Ca2 was t...Abstract Objective To investigate the theoretical model of the three-dimensional structure of mosquitocida Cry3OCa2 and its molecular docking with N-acetylgalactosamine. Methods The theoretical model of Cry30Ca2 was the Cry4Ba. Docking studies were performed N-acetylgalactosamine on the putative receptor. predicted by homology modeling on the structure of to investigate the interaction of Cry3OCa2 with Results Cry3OCa2 toxin is a rather compact molecule composed of three distinct domains and has approximate overall dimensions of 95 by 75 by 60A. Domain I is a helix bundle, Domain Ⅱ consists of three antiparallel β-sheets, Domain Ⅲ is composed of two β-sheets that adopt a 13-sandwich fold. Residue 32111e in loop1, residues 342Gin 343Thr and 345Gin in loop2, residue 393Tyr in loop3 of Cry3OCa2 are responsible for the interactions with GalNAc via 7 hydrogen bonds, 6 of them were related to the oxygen atoms of hydroxyls of the ligand, and one to the nitrogen of the ligand. Conclusion The 3D structure of Cry3OCa2 resembles the previously reported Cry toxin structures but shows still some distinctions. Several residues in the loops of the apex of domain Ⅱ are responsible for the interactions with N-acetylgalactosamine.展开更多
Examples of evolution,extinction and homoplasy of the larger benthic foraminifera(LBF)occur throughout their history.Since the Carboniferous,LBF have thrived in carbonate-rich tropical and subtropical shallow-marine s...Examples of evolution,extinction and homoplasy of the larger benthic foraminifera(LBF)occur throughout their history.Since the Carboniferous,LBF have thrived in carbonate-rich tropical and subtropical shallow-marine shelf environments.Their high abundance and diversity are due primarily to their extraordinary ability to inhabit a range of ecological niches and by hosting a variety of symbionts.Attaining relatively large,centimetre-scale sizes,made some forms very specialized and vulnerable to rapid ecological changes.For this reason,some LBF have shown a tendency to suffer periodically during major extinctions,especially when environmental conditions have changed rapidly and/or substantially.This,however,makes them valuable biostratigraphic microfossils and,in addition,gives invaluable insight into the spatial and temporal process of biological evolution,such as convergent/homoplasy and homology/iterative evolution.Here the evolutionary behavior of two important morphological types that occurred throughout the history of the LBF are discussed,namely the planispiral-fusiform test as typified by the fusulinids in the Late Paleozoic and the alveolinids in the Mid-Cretaceous and Neogene,and the three-layered discoid lenticular test as characterized by the orbitoids in the Mid-to Late Cretaceous,the orthophragminids in the Paleogene,and lepidocyclinids in the Oligocene to Quaternary.Understanding the propensity of these forms to convergent and iterative evolution,with the repeated re-occurrence of certain morphological features,is essential in understanding and constructing their phylogenetic relationships more generally within the main groups of the LBF.The insights gained from the history of these LBF have wider implications,and provide a more general understanding of the impacts of climate and ecological changes as driving forces for biological evolution.展开更多
Objective To understand the molecular basis for a potential reaction mechanism and develop novel antibiotics with homology modeling for 3-hydroxy-3-methylglutaryl coenzyme A （HMG-CoA） synthase （HMGS）. Methods The ...Objective To understand the molecular basis for a potential reaction mechanism and develop novel antibiotics with homology modeling for 3-hydroxy-3-methylglutaryl coenzyme A （HMG-CoA） synthase （HMGS）. Methods The genetic engineering technology and the composer module of SYBYL7.0 program were used, while the HMGS three-dimensional structure was analyzed by homology modeling. Results The mvaS gene was cloned from Streptococcus pneumoniae and overexpressed in Escherichia coli from a pET28 vector. The expressed enzyme （about 46 kDa） was purified by affinity chromatography with a specific activity of 3.24 μmol/min/mg. Optimal conditions were pH 9.75 and 10 mmol/L MgCl2 at 37 ℃ The Vmax and Km were 4.69 μmol/min/mg and 213 μmol/L respectively. The 3D model of S.pneumoniae HMGS was established based on structure template of HMGS of Enterococcus faecalis. Conelusion The structure of HMGS will facilitate the structure-based design of alternative drugs to cholesterol-lowering therapies or to novel antibiotics to the Gram-positive cocci, whereas the recombinant HMGS will prove useful for drug development against a different enzyme in the mevalonate pathway.展开更多
After defining the strong tensor product of strong (sub)chain complenes, it is shown that an analogue of the Kunneth theorem holds in strong homology by proving that the kernel (cokernel) of connecting homomorphisms i...After defining the strong tensor product of strong (sub)chain complenes, it is shown that an analogue of the Kunneth theorem holds in strong homology by proving that the kernel (cokernel) of connecting homomorphisms is isomorphic to the direct sum of torsion (tensor) products of strong homology groups. An isomorphism between strong (r-stage) homology groups of inverse systems is also constructed.展开更多
Currently,telecom fraud is expanding from the traditional telephone network to the Internet,and identifying fraudulent IPs is of great significance for reducing Internet telecom fraud and protecting consumer rights.Ho...Currently,telecom fraud is expanding from the traditional telephone network to the Internet,and identifying fraudulent IPs is of great significance for reducing Internet telecom fraud and protecting consumer rights.However,existing telecom fraud identification methods based on blacklists,reputation,content and behavioral characteristics have good identification performance in the telephone network,but it is difficult to apply to the Internet where IP(Internet Protocol)addresses change dynamically.To address this issue,we propose a fraudulent IP identification method based on homology detection and DBSCAN(Density-Based Spatial Clustering of Applications with Noise)clustering(DC-FIPD).First,we analyze the aggregation of fraudulent IP geographies and the homology of IP addresses.Next,the collected fraudulent IPs are clustered geographically to obtain the regional distribution of fraudulent IPs.Then,we constructed the fraudulent IP feature set,used the genetic optimization algorithm to determine the weights of the fraudulent IP features,and designed the calculation method of the IP risk value to give the risk value threshold of the fraudulent IP.Finally,the risk value of the target IP is calculated and the IP is identified based on the risk value threshold.Experimental results on a real-world telecom fraud detection dataset show that the DC-FIPD method achieves an average identification accuracy of 86.64%for fraudulent IPs.Additionally,the method records a precision of 86.08%,a recall of 45.24%,and an F1-score of 59.31%,offering a comprehensive evaluation of its performance in fraud detection.These results highlight the DC-FIPD method’s effectiveness in addressing the challenges of fraudulent IP identification.展开更多
The gene sod in Acidithiobacillusferrooxidans may play a crucial role in its tolerance to the extremely acidic, toxic and oxidative environment of bioleaching. For insight into the anti-toxic mechanism of the bacteria...The gene sod in Acidithiobacillusferrooxidans may play a crucial role in its tolerance to the extremely acidic, toxic and oxidative environment of bioleaching. For insight into the anti-toxic mechanism of the bacteria, a three-dimensional （3D） molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and its key residues were further detected by evolutionary trace analysis. Through these procedures, some trace residues were identified and spatially clustered. Among them, the residues of Asn38, Glyl03 and Glul61 are randomly scattered throughout the mapped structure; interestingly, the other residues are all distinctly clustered in a subgroup near Fe atom. From these results, this gene can be confirmed at 3D level to encode the Fe-depending superoxide dismutase and subsequently play an anti-toxic role. Furthermore, the detected key residues around Fe binding site can be conjectured to be directly responsible for Fe binding and catalytic function.展开更多
The gene iscS-3 from ,4cidithiobacillus ferrooxidans may play a central role in the delivery of sulfur to a variety of metabolic pathways in this organism. For insight into the sulfur metabolic mechanism of the bacter...The gene iscS-3 from ,4cidithiobacillus ferrooxidans may play a central role in the delivery of sulfur to a variety of metabolic pathways in this organism. For insight into the sulfur metabolic mechanism of the bacteria, an integral three-dimensional （3D） molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and further used to search bind sites, carry out flexible docking with cofactor pyridoxal 5＇-phosphate（PLP） and substrate cysteine and hereby detect its key residues. Through these procedures, the detail conformations of PLP-IscS（P-I） and cysteine-PLP-IscS（C-P-I） complexes were obtained. In P-I complex, the residues of Lys208, His106, Thr78, Ser205, His207, Asp182 and Gln185 have large interaction energies and/or hydrogen bonds fixation with PLP. In C-P-I complex, the amino group in cysteine is very near His106, Lys208 and PLP, the interaction energies for cysteine with them are very high. The above results are well consistent with those experimental facts of the homologues from other sources. Interestingly, the four residues of Glul05, Glu79, Ser203 and Hisl80 in P-I docking and the residue of Lys213 in C-P-I docking also have great interaction energies, which are fitly conservation in IscSs from all kinds of sources but have not been identified before. From these results, this gene can be confirmed at 3D level to encode the iron-sulfur cluster assembly protein IscS and subsequently play a sulfur traffic role. Furthermore, the substrate cysteine can be presumed to be effectively recruited into the active site. Finally, the above detected key residues can be conjectured to be directly responsible for the bind and/or catalysis of PLP and cysteine.展开更多
TH-98 isolate of transmissible gastroenteritis virus (TGEV) was propagated and harvested on swine testicle (ST) monolayer cell. Two pairs of primers were designed to amplify S gene by RT-PCR according to the published...TH-98 isolate of transmissible gastroenteritis virus (TGEV) was propagated and harvested on swine testicle (ST) monolayer cell. Two pairs of primers were designed to amplify S gene by RT-PCR according to the published sequence of TGEV'S gene cDNA with Oligo version 4.1 and DNasis software. The products of PCR were named Sa and Sb, of 2.3 kb and 2.1 kb respectively. Sa was inserted in EcoR I and Kpn I sites after Sb was cloned in Kpn I and Pst I multiple cloning sites of the same pUC18 plasmid. The recombinant pUC-S plasmid was identified and analyzed by corresponding restriction endonuclease and nested PCR on the basis of the genetic sites of S gene and pUC18 plasmid, which was identified as S gene of TGEV. Recombinant pUC-S was sequenced and analyzed in comparison with the other strains. Gene sequence comparison indicated that TH-98 shared 99, 97, 98, 97 and 94% identities with Purdue-115(US), Miller(US), TO14(Japan), FS772(British), 96-1933(British), respectively, their deduced amino acid homology was 99, 97, 97, 96 and 93% correspondingly. In addition, the analysis report verified that pUC-S owned a complete open reading frame (ORF) including initiation codon, signal sequences, remaining sequences and termination codon as well. Therefore, the results affirmed that S gene of TGEV TH-98 was extremely conservative.展开更多
Blastomyces dermatitidis is a thermally dimorphic fungus that causes the disease blastomycosis. Currently there are a limited number of effective treatments, many of which have harsh side effects. Chitin, a component ...Blastomyces dermatitidis is a thermally dimorphic fungus that causes the disease blastomycosis. Currently there are a limited number of effective treatments, many of which have harsh side effects. Chitin, a component of the fungal cell wall is often broken down and recycled for cell wall remodeling and growth. Chitinase is the digestive enzyme capable of chitin hydrolysis. By inhibiting the chitinase we predicted that cells wouldn’t be able to divide and multiply normally, thereby leading to possible anti-fungal treatments. For this study we modeled the structure of B. dermatitidis chitinase, using homology modeling. By predicting a three-dimensional structure we were able to do additional analyses of the active site of the chitinase and predict the binding of a possible small molecule, acetazolamide, in silico. This binding allowed us to predict that this molecule might be capable of inhibiting the chitinase of B. dermatitidis. This inhibition was tested in vivo. No difference in the growth curves of the test and control organisms was observed, however there was a difference within the cell walls of the yeast cells. The cell walls appeared thicker with additional differences in cell wall orderly growth. These changes are consistent with changes that may occur as B. dermatitidis chitinases are inhibited.展开更多
基金supported by the TARCC,Welch Foundation Award(I-1724)the Decherd Foundationthe Pape Adams Foundation,NIH grants NS092616,NS127375,NS117065,NS111776。
文摘The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.
文摘Several tritylodontid taxa have been reported from the Upper Jurassic of the Wucaiwan area in the Junggar Basin of Xinjiang,northwestern China,including Yuanotherium minor.The original study described the partially preserved postcanine teeth in the middle of the left upper maxilla.After detailed re-examination of the specimen and by CT scanning,3D reconstruction,and scanning electron microscopy observations,we provided a more detailed description of the osteology,neurosensory,and tooth wear pattern for all the bones preserved in this specimen and clarified some characters.Based on new information about the cusp wear pattern,the chewing movement pattern of the dentition and detailed cusp morphology,we discussed the cuspal homology of upper cheek teeth of tritylodontids and postulate a standardized method for cusp identification.We hypothesize that the unique maxilla characteristics furnish the evidence for transitional stages about the evolution of the upper jaw-palate structure in tritylodontids.
基金supported by the National Natural Science Foundation of China(32322079)Beijing Nova Program(20220484101)Talented Young Scientist Program,Ministry of Science and Technology of the People's Republic of China,and China Postdoctoral Science Foundation(2024M753576).
文摘Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,polyphenols,and flavonoids that contribute to its antimicrobial,antioxidant,and immuno-modulatory properties.Additionally,honey is effective in managing some conditions,such as antibiotic-resistant infections,inflammation,and oxidative stress-related diseases.This review explores the extensive health benefits of honey,emphasizing the homology between food and medicine,as proposed by TCM philosophy.Further,this review explores the traditional applications of honey in respiratory health,wound healing,and gastrointestinal support,along with modern scientific validation of these uses.Moreover,the role of honey as a dietary supplement,functional food,and preservative in culinary practices is examined.Overall,this review highlights the synergy between ancient wisdom and contemporary science,advocating for the continued exploration of the role of honey in health,nutrition,and medicine.
基金supported by National Natural Science Foundation of China(82274082 and 82204943),Beijing“high-grade,precision and advanced”Project,Beijing Key Laboratory for Basic and Development Research on Chinese Medicine.
文摘Chronic heart failure(CHF)is a pathological state in which the cardiac ejection fraction is insufficient to meet an individual's metabolic needs owing to changes in the cardiac structure or function.Various etiologies such as myocardial infarction and inflammation are implicated,and the main symptoms are dyspnea,lower limb edema,fatigue,and discomfort during rest or exercise.CHF is the primary outcome of cardiovascular disease,and the increasing morbidity and mortality rates highlight the significant risks of this condition.According to traditional Chinese medicine,the pathogenesis of CHF is deficiency of heart qi and heart yang,which predominantly affects the heart,but may also impede the function of other zang-organs such as the spleen and kidney,and aggravate the symptoms of heart failure.With technological advancements and enhanced awareness of health conditions and disease prevention,China has promoted traditional medicine practices such as medicine and food homology(MFH),which has received increasing attention in recent years.This concept stipulates that certain medicines and foods have the same origin;ergo,these foods have medicinal properties,with many being used in the pre-vention and treatment of CHF.However,the efficacy and safety of MHF substances have yet to be determined,and there is no consensus regarding the development of disease prevention and treatment strategies.This article therefore reviews the current evidence for MFH in the prevention and treatment of CHF by summarizing the therapeutic potential of this practice and discussing treatment strategies and aims to improve the understanding of Chinese medicine and food homologous substances in the treatment of this condition,as well as highlight the current literature and avenues for future research.
文摘pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical properties, hydrophilicity/hydrophobicity, signal peptide, secondary structure, coiled coil, transmembrane domains, O-glycogylation site, active site, subcellular localization, functional structural domains and three-dimensional structure were analyzed by a series of bioinformatics software. The results showed that mPDI was a hydrophobic and stable protein with 3 coiled coils, 30-glycogylation sites, 2 structural domains of thioredoxin, 2 active sites of thioredoxin, and located in rough endoplasmic reticulum. It has 512 amino acids, the theoretical pl is 4.98, and signal peptide located in 1-24AA. In the secondary structure, a-helix, random coil, extended chain is 26.37%, 53.32%, 20.31% respectively. The validation of modeling accords with the stereochemistry.
文摘Rice metallothionein-like protein (rgMT) shows characteristics of a three-section pattern composed of two highly conserved cysteine rich (CR) domains in the terminals and a spacer without cysteine (cys) residues in the center of the molecule. In this paper, the two CR domains and the spacer region were modeled by the distance geometry and homology methods separately. For the CR domains, twenty random models were generated for each cys combination based on the constraint conditions of CXC (C represents cys, X represents any amino acid other than cys), and CXXC motifs and a metal-sulfur chelating cluster. Four models for the N-terminal and two for C-terminal CR domain containing metal chelating structures formed by different combinations of cys were selected from 900 possible conformations. The GOR method was used to predict the secondary structure of the spacer region and its model was built by the homology method. After three parts of the protein were modeled, they were connected to form a three-dimensional structure model of rgMT. The whole conformation showed that rgMT could form two independent metal-sulfur chelating structures connected by a spacer peptide, without a structural or energy barrier for them to form two independent metal-chelating clusters just as mammalian metallothionein (MT) proteins. As all plant metallothionein-like (MT-L) proteins have the same primary structural characteristic, two CR domains connected by a spacer region, and many have the same cys arrangement pattern as rgMT, the three-dimensional structure model of rgMT will provide an important reference for the structural study of other plant MT-L proteins.
文摘Let A be a tame Hecke algebra of type A. A new minimal projective bimodule resolution for A is constructed and the dimensions of all the Hochschild homology groups and cyclic homology groups are calculated explicitly.
文摘In this paper, we propose a new algorithm to compute the homology of a finitely generated chain complex. Our method is based on grouping several reductions into structures that can be encoded as directed acyclic graphs. The organized reduction pairs lead to sequences of projection maps that reduce the number of generators while preserving the homology groups of the original chain complex. This sequencing of reduction pairs allows updating the boundary information in a single step for a whole set of reductions, which shows impressive gains in computational performance compared to existing methods. In addition, our method gives the homology generators for a small additional cost.
基金supported by a Collaborative Funding Grant from North Carolina Biotechnology Center and Syngenta Biotechnology (2016-CFG-8003)startup funds provided by East Carolina University and University of Maryland to Y.Q.a grant from the National Science Foundation (IOS-1339209)
文摘Breakthroughs in the generation of programmable sequence-specific nucleases (SSNs), such as zinc finger nucleases (ZFNs),TAL effector nucleases (TALENs) and the RNA-directed nuclease CRISPR-associated protein 9 (Cas9), have greatly increased the ease of plant genome engineering (Voytas, 2013; Malzahn et al.,2017). Programmable SSNs introduce a DNA double-strand break
文摘Detecting remote homology proteins is a challenging problem for both basic research and drug development. Although there are a couple of methods to deal with this problem, the benchmark datasets based on which the existing methods were trained and tested contain many high homologous samples as reflected by the fact that the cutoff threshold was set at 95%. In this study, we reconstructed the benchmark dataset by setting the threshold at 40%, meaning none of the proteins included in the benchmark dataset has more than 40% pairwise sequence identity with any other in the same subset. Using the new benchmark dataset, we proposed a new predictor called “dRHP-GreyFun” based on the grey modeling and functional domain approach. Rigorous cross-validations have indicated that the new predictor is superior to its counterparts in both enhancing success rates and reducing computational cost. The predictor can be downloaded from https://github.com/jcilwz/dRHP-GreyFun.
文摘<abstract>Aim: Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the rat. Methods: 'Electronic screening' of Expressed Sequence Tag (EST) and genomic databases, followed by RT-PCR and Northern blot analysis. Results: Rodent ESTs and genomic sequences homologous to HE3, HE4 and Ce8/Ly6G5C were identified in the public databases and the 'full-length' rat cDNAs cloned. To emphasise their homology to the human and canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat counterparts, respectively. mRNA expression patterns were analysed in rats, including rat HEl and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were only found in the rat epididymis, while Re4 showed a broader tissue distribution. Within the epididymis, Re3 and Re4 mRNAs were detected in all regions; Re8, on the other hand, was restricted to the caput. During postnatal development, Re3 and control mRNAs were found from the earliest stages investigated, while Re8 mRNA was observed only from day 24 postnatum, corresponding to the onset of spermatogenesis in the prepubertal testis. Castration and testosterone supplementation of adult male rats suggested that none of the cloned mRNAs was directly androgen-regulated. Efferent duct ligation, however, showed that Re8 mRNA levels depended on testicular factors other than androgens. Conclusion: The novel rodent cDNAs can now be used to monitor epididymal gene expression more closely and to set up various regulatory and functional studies.
基金supported by grants from Hunan Provincial Natural Science Foundation of China(No.12JJ3021)the National Natural Science Foundation of China(No.30670052,30570050)863 Program of China(2006AA02Z187)
文摘Abstract Objective To investigate the theoretical model of the three-dimensional structure of mosquitocida Cry3OCa2 and its molecular docking with N-acetylgalactosamine. Methods The theoretical model of Cry30Ca2 was the Cry4Ba. Docking studies were performed N-acetylgalactosamine on the putative receptor. predicted by homology modeling on the structure of to investigate the interaction of Cry3OCa2 with Results Cry3OCa2 toxin is a rather compact molecule composed of three distinct domains and has approximate overall dimensions of 95 by 75 by 60A. Domain I is a helix bundle, Domain Ⅱ consists of three antiparallel β-sheets, Domain Ⅲ is composed of two β-sheets that adopt a 13-sandwich fold. Residue 32111e in loop1, residues 342Gin 343Thr and 345Gin in loop2, residue 393Tyr in loop3 of Cry3OCa2 are responsible for the interactions with GalNAc via 7 hydrogen bonds, 6 of them were related to the oxygen atoms of hydroxyls of the ligand, and one to the nitrogen of the ligand. Conclusion The 3D structure of Cry3OCa2 resembles the previously reported Cry toxin structures but shows still some distinctions. Several residues in the loops of the apex of domain Ⅱ are responsible for the interactions with N-acetylgalactosamine.
文摘Examples of evolution,extinction and homoplasy of the larger benthic foraminifera(LBF)occur throughout their history.Since the Carboniferous,LBF have thrived in carbonate-rich tropical and subtropical shallow-marine shelf environments.Their high abundance and diversity are due primarily to their extraordinary ability to inhabit a range of ecological niches and by hosting a variety of symbionts.Attaining relatively large,centimetre-scale sizes,made some forms very specialized and vulnerable to rapid ecological changes.For this reason,some LBF have shown a tendency to suffer periodically during major extinctions,especially when environmental conditions have changed rapidly and/or substantially.This,however,makes them valuable biostratigraphic microfossils and,in addition,gives invaluable insight into the spatial and temporal process of biological evolution,such as convergent/homoplasy and homology/iterative evolution.Here the evolutionary behavior of two important morphological types that occurred throughout the history of the LBF are discussed,namely the planispiral-fusiform test as typified by the fusulinids in the Late Paleozoic and the alveolinids in the Mid-Cretaceous and Neogene,and the three-layered discoid lenticular test as characterized by the orbitoids in the Mid-to Late Cretaceous,the orthophragminids in the Paleogene,and lepidocyclinids in the Oligocene to Quaternary.Understanding the propensity of these forms to convergent and iterative evolution,with the repeated re-occurrence of certain morphological features,is essential in understanding and constructing their phylogenetic relationships more generally within the main groups of the LBF.The insights gained from the history of these LBF have wider implications,and provide a more general understanding of the impacts of climate and ecological changes as driving forces for biological evolution.
基金supported by the National Natural Science Foundation of China (No. 30771429)Science and Technology Research Project of Ministry of Education (No.106116)+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education (No. 20060511002)the Natural Science Foundation of Hubei Province (No. 2006ABA197)
文摘Objective To understand the molecular basis for a potential reaction mechanism and develop novel antibiotics with homology modeling for 3-hydroxy-3-methylglutaryl coenzyme A （HMG-CoA） synthase （HMGS）. Methods The genetic engineering technology and the composer module of SYBYL7.0 program were used, while the HMGS three-dimensional structure was analyzed by homology modeling. Results The mvaS gene was cloned from Streptococcus pneumoniae and overexpressed in Escherichia coli from a pET28 vector. The expressed enzyme （about 46 kDa） was purified by affinity chromatography with a specific activity of 3.24 μmol/min/mg. Optimal conditions were pH 9.75 and 10 mmol/L MgCl2 at 37 ℃ The Vmax and Km were 4.69 μmol/min/mg and 213 μmol/L respectively. The 3D model of S.pneumoniae HMGS was established based on structure template of HMGS of Enterococcus faecalis. Conelusion The structure of HMGS will facilitate the structure-based design of alternative drugs to cholesterol-lowering therapies or to novel antibiotics to the Gram-positive cocci, whereas the recombinant HMGS will prove useful for drug development against a different enzyme in the mevalonate pathway.
文摘After defining the strong tensor product of strong (sub)chain complenes, it is shown that an analogue of the Kunneth theorem holds in strong homology by proving that the kernel (cokernel) of connecting homomorphisms is isomorphic to the direct sum of torsion (tensor) products of strong homology groups. An isomorphism between strong (r-stage) homology groups of inverse systems is also constructed.
基金funded by the National Natural Science Foundation of China under Grant No.62002103Henan Province Science Foundation for Youths No.222300420058+1 种基金Henan Province Science and Technology Research Project No.232102321064Teacher Education Curriculum Reform Research Priority Project No.2023-JSJYZD-011.
文摘Currently,telecom fraud is expanding from the traditional telephone network to the Internet,and identifying fraudulent IPs is of great significance for reducing Internet telecom fraud and protecting consumer rights.However,existing telecom fraud identification methods based on blacklists,reputation,content and behavioral characteristics have good identification performance in the telephone network,but it is difficult to apply to the Internet where IP(Internet Protocol)addresses change dynamically.To address this issue,we propose a fraudulent IP identification method based on homology detection and DBSCAN(Density-Based Spatial Clustering of Applications with Noise)clustering(DC-FIPD).First,we analyze the aggregation of fraudulent IP geographies and the homology of IP addresses.Next,the collected fraudulent IPs are clustered geographically to obtain the regional distribution of fraudulent IPs.Then,we constructed the fraudulent IP feature set,used the genetic optimization algorithm to determine the weights of the fraudulent IP features,and designed the calculation method of the IP risk value to give the risk value threshold of the fraudulent IP.Finally,the risk value of the target IP is calculated and the IP is identified based on the risk value threshold.Experimental results on a real-world telecom fraud detection dataset show that the DC-FIPD method achieves an average identification accuracy of 86.64%for fraudulent IPs.Additionally,the method records a precision of 86.08%,a recall of 45.24%,and an F1-score of 59.31%,offering a comprehensive evaluation of its performance in fraud detection.These results highlight the DC-FIPD method’s effectiveness in addressing the challenges of fraudulent IP identification.
基金Project(2004CB619201) supported by the National Basic Research Program of ChinaProject (50321402) supported by the National Natural Science Foundation of China
文摘The gene sod in Acidithiobacillusferrooxidans may play a crucial role in its tolerance to the extremely acidic, toxic and oxidative environment of bioleaching. For insight into the anti-toxic mechanism of the bacteria, a three-dimensional （3D） molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and its key residues were further detected by evolutionary trace analysis. Through these procedures, some trace residues were identified and spatially clustered. Among them, the residues of Asn38, Glyl03 and Glul61 are randomly scattered throughout the mapped structure; interestingly, the other residues are all distinctly clustered in a subgroup near Fe atom. From these results, this gene can be confirmed at 3D level to encode the Fe-depending superoxide dismutase and subsequently play an anti-toxic role. Furthermore, the detected key residues around Fe binding site can be conjectured to be directly responsible for Fe binding and catalytic function.
基金Project(2004CB619201) supported by the National Basic Research Program of China Project(50321402) supported by the National Natural Science Foundation of China
文摘The gene iscS-3 from ,4cidithiobacillus ferrooxidans may play a central role in the delivery of sulfur to a variety of metabolic pathways in this organism. For insight into the sulfur metabolic mechanism of the bacteria, an integral three-dimensional （3D） molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and further used to search bind sites, carry out flexible docking with cofactor pyridoxal 5＇-phosphate（PLP） and substrate cysteine and hereby detect its key residues. Through these procedures, the detail conformations of PLP-IscS（P-I） and cysteine-PLP-IscS（C-P-I） complexes were obtained. In P-I complex, the residues of Lys208, His106, Thr78, Ser205, His207, Asp182 and Gln185 have large interaction energies and/or hydrogen bonds fixation with PLP. In C-P-I complex, the amino group in cysteine is very near His106, Lys208 and PLP, the interaction energies for cysteine with them are very high. The above results are well consistent with those experimental facts of the homologues from other sources. Interestingly, the four residues of Glul05, Glu79, Ser203 and Hisl80 in P-I docking and the residue of Lys213 in C-P-I docking also have great interaction energies, which are fitly conservation in IscSs from all kinds of sources but have not been identified before. From these results, this gene can be confirmed at 3D level to encode the iron-sulfur cluster assembly protein IscS and subsequently play a sulfur traffic role. Furthermore, the substrate cysteine can be presumed to be effectively recruited into the active site. Finally, the above detected key residues can be conjectured to be directly responsible for the bind and/or catalysis of PLP and cysteine.
文摘TH-98 isolate of transmissible gastroenteritis virus (TGEV) was propagated and harvested on swine testicle (ST) monolayer cell. Two pairs of primers were designed to amplify S gene by RT-PCR according to the published sequence of TGEV'S gene cDNA with Oligo version 4.1 and DNasis software. The products of PCR were named Sa and Sb, of 2.3 kb and 2.1 kb respectively. Sa was inserted in EcoR I and Kpn I sites after Sb was cloned in Kpn I and Pst I multiple cloning sites of the same pUC18 plasmid. The recombinant pUC-S plasmid was identified and analyzed by corresponding restriction endonuclease and nested PCR on the basis of the genetic sites of S gene and pUC18 plasmid, which was identified as S gene of TGEV. Recombinant pUC-S was sequenced and analyzed in comparison with the other strains. Gene sequence comparison indicated that TH-98 shared 99, 97, 98, 97 and 94% identities with Purdue-115(US), Miller(US), TO14(Japan), FS772(British), 96-1933(British), respectively, their deduced amino acid homology was 99, 97, 97, 96 and 93% correspondingly. In addition, the analysis report verified that pUC-S owned a complete open reading frame (ORF) including initiation codon, signal sequences, remaining sequences and termination codon as well. Therefore, the results affirmed that S gene of TGEV TH-98 was extremely conservative.
文摘Blastomyces dermatitidis is a thermally dimorphic fungus that causes the disease blastomycosis. Currently there are a limited number of effective treatments, many of which have harsh side effects. Chitin, a component of the fungal cell wall is often broken down and recycled for cell wall remodeling and growth. Chitinase is the digestive enzyme capable of chitin hydrolysis. By inhibiting the chitinase we predicted that cells wouldn’t be able to divide and multiply normally, thereby leading to possible anti-fungal treatments. For this study we modeled the structure of B. dermatitidis chitinase, using homology modeling. By predicting a three-dimensional structure we were able to do additional analyses of the active site of the chitinase and predict the binding of a possible small molecule, acetazolamide, in silico. This binding allowed us to predict that this molecule might be capable of inhibiting the chitinase of B. dermatitidis. This inhibition was tested in vivo. No difference in the growth curves of the test and control organisms was observed, however there was a difference within the cell walls of the yeast cells. The cell walls appeared thicker with additional differences in cell wall orderly growth. These changes are consistent with changes that may occur as B. dermatitidis chitinases are inhibited.
