The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization.In order to uncover clues about the determinants for virulence and p...The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization.In order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza viruses.We analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other subtypes.We compared their differences and similarities systematically.Based on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,6-receptor.The D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported work.This HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion function.The 2009 S-OIV HA also has an extra glycosylation site at position 276.Four of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation site.The previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were defined.These results are critical for understanding the pathogenicity of the virus and host immune response against the virus.展开更多
目的比较3种沙门菌分子血清分型方法,获得一种准确度较高的方法用来替代传统的血清凝集技术用于沙门菌血清型判定。方法对覆盖50个血清型的509株沙门菌提取核酸进行全基因组测序,根据全基因组序列分别利用多位点序列分型(MLST)、SalmonS...目的比较3种沙门菌分子血清分型方法,获得一种准确度较高的方法用来替代传统的血清凝集技术用于沙门菌血清型判定。方法对覆盖50个血清型的509株沙门菌提取核酸进行全基因组测序,根据全基因组序列分别利用多位点序列分型(MLST)、SalmonSeroPredicition以及SISTR(Salmonella in silico typing resource)3种方法在线预测获得每株菌的血清型,然后与传统血清凝集获得的血清型进行一致性比较分析,评估每种方法血清型预测的准确度。结果SISTR、MLST以及SalmonSeroPredicition预测血清型的准确率分别为96.67%、93.52%、69.16%。常见沙门菌血清型印第安纳沙门菌和鼠伤寒沙门菌血清型预测正确率最高,为100%,德尔卑沙门菌、肠炎沙门菌血清型预测正确率分别为99.17%、95.74%。3种方法均预测错误的血清型有肠炎沙门菌、德尔卑沙门菌和沙门菌的萨拉姆亚种、亚利桑那亚种和双相亚利桑那亚种等;预测错误原因主要是基因序列丢失和鞭毛抗原基因未表达。结论基于基因组序列的SISTR血清型预测方法具有较高的血清型预测准确度,在传统血清凝集难以开展或沙门菌鞭毛基因不表达的情况下,可以替代血清凝集试验进行沙门菌血清型判定。展开更多
Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologie...Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologies due to excessive inflammation.Professional phagocytes such as neutrophils(PMNs),eosinophils,monocytes,and macrophages use superoxide-generating NADPH oxidase(NOX)as part of their arsenal of antimicrobial mechanisms to produce high levels of ROS.NOX is a multisubunit enzyme complex composed of five essential subunits,two of which are localized in the membrane,while three are localized in the cytosol.In resting phagocytes,the oxidase complex is unassembled and inactive;however,it becomes activated after cytosolic components translocate to the membrane and are assembled into a functional oxidase.The NOX isoforms play a variety of roles in cellular differentiation,development,proliferation,apoptosis,cytoskeletal control,migration,and contraction.Recent studies have identified NOX as a major contributor to disease pathologies,resulting in a shift in focus on inhibiting the formation of potentially harmful free radicals.Therefore,a better understanding of the molecular mechanisms and the transduction pathways involved in NOX-mediated signaling is essential for the development of new therapeutic agents that minimize the hyperproduction of ROS.The current review provides a thorough overview of the various NOX enzymes and their roles in disease pathophysiology,highlights pharmacological strategies,and discusses the importance of computational modeling for future NOX-related studies.展开更多
A doubled haploid （DH） population, which consists of 120 lines derived from anther culture of a typical indica and japonica hybrid‘CJ06＇/‘TNI＇, was used in this study. Ligule lengths of flag leaf were investigat...A doubled haploid （DH） population, which consists of 120 lines derived from anther culture of a typical indica and japonica hybrid‘CJ06＇/‘TNI＇, was used in this study. Ligule lengths of flag leaf were investigated for quantitative trait loci （QTL） mapping using the DH population. Five QTLs （qLL-2, qLL.4, qLL-6, qLL-IO and qLL-12） controlling the ligule length （LL） were detected on chromosomes 2, 4, 6, 10 and 12, with the variances explained 11.4%, 13.6%, 27.8%, 22.1% and 11.0%, respectively. Using four known genes of ZmGL1, ZmGL2, ZmGL3 and ZmGL4 in maize from the MaizeGDB, their homologs in rice were aligned and integrated into the existing simple sequence repeats linkage map by in silico mapping. A ZmLG1 homolog gene, OsLG1 encoding a squamosa promoter binding protein, was located between the markers RM255 and RM280, which is just identical to the interval of qLL.4 on the long arm of chromosome 4. The results are beneficial to dissection of the ligule molecular mechanism and the study of cereal evolution.展开更多
To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients. METHODSColonic mucosal pinch biopsies were analyzed from the i...To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients. METHODSColonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted. RESULTSThe miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC. CONCLUSIONThe present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.展开更多
There are many studies on enzymatic pathways of anthocyanin biosynthesis, but little is known about the anthocyanins transport in Oryze sativa. In silico analysis, the OsMRP15 (LOC_Os06g06440), an orthologous gene of ...There are many studies on enzymatic pathways of anthocyanin biosynthesis, but little is known about the anthocyanins transport in Oryze sativa. In silico analysis, the OsMRP15 (LOC_Os06g06440), an orthologous gene of mazie anthocyanin transporter ZmMRP3, has been identified in rice. The OsMRP15 contained a 4425bp open reading frame (ORF) encoding a 1475 amino acid protein, belonging to a MRP subfamily of ABC transporters, and has a high sequence identity, very similar protein structure, and the same arrangement of domains to ZmMRP3, but the genomic structure of OsMRP15 was significant difference with ZmMRP3. The prediction promoter of OsMRP15 has many presumed anthocyanin regulatory sites. The phylogenetic analysis of MRPs in rice, mazie and Arabidopsis showed that OsMRP15 and ZmMRP3 belonged to the same subbranch. The expression pattern indicated that OsMRP15 was co-expression with two anthocyanin transcription factors. These analysis results implied that as an ortholog of ZmMRP3, the function of OsMRP15 was possibly as a membrane-bound transporter required for vacuolar uptake of anthocyanins in rice.展开更多
Pathogenesis-related proteins （PRs） play many important roles in plant defense response against pathogen attack. To better understand the molecular mechanism of PR genes involved in wheat adult plant resistance （AP...Pathogenesis-related proteins （PRs） play many important roles in plant defense response against pathogen attack. To better understand the molecular mechanism of PR genes involved in wheat adult plant resistance （APR） to stripe rust, based on a differentially expressed transcribed derived fragment （TDF）, a novel PR gene from wheat cv. Xingzi 9104 infected by the Puccinia striiformis Westend f. sp. tritici Erikss. pathotype CY32, which was highly similar to the maize ZmPRIO gene and designated as TaPRIO, was identified using in silico cloning and RT-PCR method. This novel TaPRIO gene was predicted to encode a 160-amino acid protein with a deduced molecular weight of 17.06 kDa and an isoelectronic point （pI） of 5.19. An amino acid sequence analysis of TaPR10 demonstrated the presence of a typical conserved domain of pathogenesis related protein Bet v I family. Multiple alignment analysis based on the amino acids encoded by 10 different PRIO genes from maize （Zea mays）, rice （Oryza sativa）, broomcorn （Sorghum bicolor）, and wheat （Triticum aestivum） indicated that PR proteins of class 10 was conserved among the 4 plant species with about 80% similarity. DNA sequence of TaPRIO suggested the presence of one 84-bp intron with the splicing sites of GT-AT bi-nucleotide sequence between 188 and 271 bp. Using a real-time quantitative RT-PCR （qRT-PCR）, expression profiles of TaPRIO revealed that at the adult-plant stage, TaPRIO transcript was up-regulated as early as 12 h post-inoculation （hpi）, with the occurrence of maximum induction at 24 hpi. At the seedling stage, TaPRIO was also slightly induced 18 hpi. However, the transcript amount was relatively lower than that of the adult-plant stage. Taken together, these results suggest that TaPRIO may participate in wheat defense response of APR to stripe rust.展开更多
Lipid-based formulations(LBFs)have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.However,construction of in vitro and in vivo correlations(IVIVCs)for LBFs is quite chall...Lipid-based formulations(LBFs)have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.However,construction of in vitro and in vivo correlations(IVIVCs)for LBFs is quite challenging,owing to a complex in vivo processing of these formulations.In this paper,we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption;based on the concept of IVIVCs,the current status of in vitro models to establish IVIVCs for LBFs is reviewed,while future perspectives in this field are discussed.In vitro tests,which facilitate the understanding and prediction of the in vivo performance of solid dosage forms,frequently fail to mimic the in vivo processing of LBFs,leading to inconsistent results.In vitro digestion models,which more closely simulate gastrointestinal physiology,are a more promising option.Despite some successes in IVIVC modeling,the accuracy and consistency of these models are yet to be validated,particularly for human data.A reliable IVIVC model can not only reduce the risk,time,and cost of formulation development but can also contribute to the formulation design and optimization,thus promoting the clinical translation of LBFs.展开更多
This study aimed to identify novel ACEI peptides from Larimichthys crocea titin using in silico approaches and to clarify the molecular interaction mechanism.The hydrolyzed peptides of titin were compared with known A...This study aimed to identify novel ACEI peptides from Larimichthys crocea titin using in silico approaches and to clarify the molecular interaction mechanism.The hydrolyzed peptides of titin were compared with known ACEI peptides in the AHTPDB and BIOPEP-UWM database.Furthermore,peptides were evaluated for their solubility,ADMET properties,ΔG(kcal/mol)values,and in vitro ACEI activity.Molecular mechanism of ACE-peptide was performed by molecular interactions and binding orientation study.The results revealed that IC50 values of Trp-Ala-Arg(WAR)and Trp-Gln-Arg(WQR)were(31.2±0.8)and(231.33±0.02)mol/L,respectively.The docking interactions result suggested that ACE-WAR and ACEWQR complexes have same binding site,including the residues LYS511,TYR520,TYR523,HIS353,and HIS513.Molecular docking of two tripeptides WAR and WQR with ACE studies predicted their binding site and clarified the interaction between ACE and its inhibitors.The molecular docking data are consistent with the ACE inhibitory activity of the studied peptides.The results showed that Larimichthys crocea titin may be a valuable source for developing nutraceutical food.展开更多
Human fibrinogen-related protein-1/liver fibrinogen-related protein-1 (HFREP-l/LFIRE-1), a liver-specific protein, is a member of fibrinogen superfamily that exerts various biological activities. However, the function...Human fibrinogen-related protein-1/liver fibrinogen-related protein-1 (HFREP-l/LFIRE-1), a liver-specific protein, is a member of fibrinogen superfamily that exerts various biological activities. However, the function of HFREP-l/LFIRE-1 in liver remains unknown. Here we isolated its mouse ortholog gene-mouse fibrinogen-related protein-1 (mfrep-1), which encoded 314 amino acids, exhibiting 80.4% similarity to HFREP-l/LFIRE-1. Northern blot analysis revealed that 1.2-kb mfrep-1 mRNA was detected selectively in mouse liver. To explore the function of MFREP-1, we examined the levels of mfrep-1 mRNA during regeneration after 70% partial hepatectomy (PHx) in mice, mfrep-1 mRNA increased in the regenerating liver and reached the first shoulder peak at 2-4 h after PHx. Cycloheximide pretreatment could suppress the induction of mfrep-1, indicating the up-regulation of this gene need de novo protein synthesis. Its mRNA continued to elevate at 6 h thereafter and reached the second peak at 24 h. The enhanced expression of mfrep-1 maintained high until 72 h and then declined slowly to the basal level. Immunohistochemistry assessment confirmed the up-regulated expression of MFREP-1 protein in parenchymal cells during liver regeneration. These data suggested that MFREP-1 might play an important role in liver regeneration and be involved in the regulation of cell growth.展开更多
Objective： To elucidate the action mechanism of Xingnaojing Injection （醒脑静注射液, XNJI） for sepsis, and to target screen the potential bioactive ingredients. Methods： An integrated protocol that combines in sil...Objective： To elucidate the action mechanism of Xingnaojing Injection （醒脑静注射液, XNJI） for sepsis, and to target screen the potential bioactive ingredients. Methods： An integrated protocol that combines in silico target screen （molecular docking） and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target （C-T） interaction network. The XNJI＇s bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-1ipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction. Results： Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment. Conclusions： The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.展开更多
Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency mo...Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.展开更多
Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, H...Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, HMPREF3221_01179, derived from F. nucleatum strain MJR7757B, employing various computational methods to anticipate both its structure and functional characteristics. NCBI conserved domain analysis, NCBI BLASTp and MEGA Phylogenetic tree study characterize the target protein as an outer membrane efflux protein (ToIC family) which facilitate the bacterial transmembrane transport. With a molecular weight of 52120.02 Da, an isoelectric point (pI) of 8.33, and an instability index of 29.47, the protein is anticipated to exhibit good solubility in the extracellular space and crucial stability for pharmaceutical applications. The protein’s structure meets quality standards during the construction and refinement of its 3D model. The efflux inhibitor Arginine beta-naphthylamide exhibits a significant binding affinity (-7.1 kcal/mol) to the binding site of the target protein. The in-silico analysis improves the understanding of the protein and facilitates future investigations into therapeutic medication.展开更多
Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study lever...Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study leverages computational tools to dissect the differential gene expression profiles in retinoblastoma. Methods: Employing an in silico approach, we analyzed gene expression data from public repositories by applying rigorous statistical models, including limma and de seq 2, for identifying differentially expressed genes DEGs. Our findings were validated through cross-referencing with independent datasets and existing literature. We further employed functional annotation and pathway analysis to elucidate the biological significance of these DEGs. Results: Our computational analysis confirmed the dysregulation of key retinoblastoma-associated genes. In comparison to normal retinal tissue, RB1 exhibited a 2.5-fold increase in expression (adjusted p Conclusions: Our analysis reinforces the critical genetic alterations known in retinoblastoma and unveils new avenues for research into the disease’s molecular basis. The discovery of chemoresistance markers and immune-related genes opens potential pathways for personalized treatment strategies. The study’s outcomes emphasize the power of in silico analyses in unraveling complex cancer genomics.展开更多
Background： The increase in global population, climate change and stagnancy in crop yield on unit land area basis in recent decades urgently call for a new approach to support contemporary crop improvements, ePlant i...Background： The increase in global population, climate change and stagnancy in crop yield on unit land area basis in recent decades urgently call for a new approach to support contemporary crop improvements, ePlant is a mathematical model of plant growth and development with a high level of mechanistic details to meet this challenge. Results： ePlant integrates modules developed for processes occurring at drastically different temporal （10-8-106 seconds） and spatial （10-10-10 meters） scales, incorporating diverse physical, biophysical and biochemical processes including gene regulation, metabolic reaction, substrate transport and diffusion, energy absorption, transfer and conversion, organ morphogenesis, plant environment interaction, etc. Individual modules are developed using a divide-and-conquer approach; modules at different temporal and spatial scales are integrated through transfer variables. We further propose a supervised learning procedure based on information geometry to combine model and data for both knowledge discovery and model extension or advances. We finally discuss the recent formation of a global consortium, which includes experts in plant biology, computer science, statistics, agronomy, phenomics, etc. aiming to expedite the development and application of ePlant or its equivalents by promoting a new model development paradigm where models are developed as a community effort instead of driven mainly by individual labs＇ effort. Conclusions： ePlant, as a major research tool to support quantitative and predictive plant science research, will play a crucial role in the future model guided crop engineering, breeding and agronomy.展开更多
The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was establishe...The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR and mass spectroscopy. These new compounds were tested for their antiproliferative activities on seven representative human tumoral cell lines (Huh7 D12, Caco2, MDA-MB231, MDA-MB468, HCT116, PC3 and MCF7) and also on fibroblasts. Among them, only the compounds 6c showed micromolar cytotoxic activity on tumor cell lines (1.8 50 50 > 25 μM). Finally, in silico ADMET studies ware performed to investigate the possibility of using of the identified compound 6c as potential anti-tumor compound.展开更多
Background: Cosmetic formulations, and particularly solar products which contain mineral and chemical UV-filters, are often suspected of causing harmful effects on marine fauna and flora. After the publication of our ...Background: Cosmetic formulations, and particularly solar products which contain mineral and chemical UV-filters, are often suspected of causing harmful effects on marine fauna and flora. After the publication of our work in 2019 concerning the ecotoxicological effects of such formulations on corals (Seriatopora hystrix), we here provide some new information about the biodegradability and the ecotoxicological effects of these products on marine zoo- and phytoplankton. Therefore, we choose to realize in silico and in vitro studies of the biodegradability of several solar products but also to evaluate the ecotoxicological effects of these products on one phytoplankton, i.e. Phaeodactylum tricornutum, and one zooplankton, i.e. Acartia tonsa, of a great importance for sea species survival (notably as sources of food). Materials and methods: Two different approaches were used to study the biodegradability of the tested products: One in silico method and an in vitro one. 2 solar products were involved in the in silico study which consisted in the determination of the degradation factor (DF) of each ingredient of the tested formulas in order to finally obtain their estimated biodegradability percentage. Already available data concerning each ingredient coupled to a computer model developed with one of our partners were used to achieve this study. The in vitro study involved 8 formulas containing UV-filters and was led by following the OECD 301 F guidelines. Ecotoxicological studies of 7 of the formulas containing UV-filters were for their part realized by following the ISO 10253 guidelines for the experiments led with Phaeodactylum tricornutum, and the ISO 14669 guidelines for the experiments led with Acartia tonsa. In these studies, the effect of each tested product on crustaceans’ mortality and algal growth inhibition was assessed. Results: The in silico study predicted that formulas containing chemical UV-filters display a high biodegradability (superior to the threshold value of 60% given by the OECD 301 F guideli展开更多
基金supported by the National Basic Research Program of China (Grant No. 2010CB534004)an intramural grant from the Chinese Academy of Sciences (Grant No. KSCX2-YW-R-158)
文摘The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization.In order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza viruses.We analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other subtypes.We compared their differences and similarities systematically.Based on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,6-receptor.The D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported work.This HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion function.The 2009 S-OIV HA also has an extra glycosylation site at position 276.Four of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation site.The previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were defined.These results are critical for understanding the pathogenicity of the virus and host immune response against the virus.
文摘目的比较3种沙门菌分子血清分型方法,获得一种准确度较高的方法用来替代传统的血清凝集技术用于沙门菌血清型判定。方法对覆盖50个血清型的509株沙门菌提取核酸进行全基因组测序,根据全基因组序列分别利用多位点序列分型(MLST)、SalmonSeroPredicition以及SISTR(Salmonella in silico typing resource)3种方法在线预测获得每株菌的血清型,然后与传统血清凝集获得的血清型进行一致性比较分析,评估每种方法血清型预测的准确度。结果SISTR、MLST以及SalmonSeroPredicition预测血清型的准确率分别为96.67%、93.52%、69.16%。常见沙门菌血清型印第安纳沙门菌和鼠伤寒沙门菌血清型预测正确率最高,为100%,德尔卑沙门菌、肠炎沙门菌血清型预测正确率分别为99.17%、95.74%。3种方法均预测错误的血清型有肠炎沙门菌、德尔卑沙门菌和沙门菌的萨拉姆亚种、亚利桑那亚种和双相亚利桑那亚种等;预测错误原因主要是基因序列丢失和鞭毛抗原基因未表达。结论基于基因组序列的SISTR血清型预测方法具有较高的血清型预测准确度,在传统血清凝集难以开展或沙门菌鞭毛基因不表达的情况下,可以替代血清凝集试验进行沙门菌血清型判定。
基金This work was supported by the Young Clinical Scientist Award from the Flight Attendant Medical Research Institute(FAMRI-123253_YCSA_Faculty)
文摘Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologies due to excessive inflammation.Professional phagocytes such as neutrophils(PMNs),eosinophils,monocytes,and macrophages use superoxide-generating NADPH oxidase(NOX)as part of their arsenal of antimicrobial mechanisms to produce high levels of ROS.NOX is a multisubunit enzyme complex composed of five essential subunits,two of which are localized in the membrane,while three are localized in the cytosol.In resting phagocytes,the oxidase complex is unassembled and inactive;however,it becomes activated after cytosolic components translocate to the membrane and are assembled into a functional oxidase.The NOX isoforms play a variety of roles in cellular differentiation,development,proliferation,apoptosis,cytoskeletal control,migration,and contraction.Recent studies have identified NOX as a major contributor to disease pathologies,resulting in a shift in focus on inhibiting the formation of potentially harmful free radicals.Therefore,a better understanding of the molecular mechanisms and the transduction pathways involved in NOX-mediated signaling is essential for the development of new therapeutic agents that minimize the hyperproduction of ROS.The current review provides a thorough overview of the various NOX enzymes and their roles in disease pathophysiology,highlights pharmacological strategies,and discusses the importance of computational modeling for future NOX-related studies.
基金Supported by the State Key Basic Research and Development Plan ofChina(2007CB10920203)the National Natural Science Foundation of China(30771160,30571136)+1 种基金the Open Fund of State Key Laboratory of RiceBiology(080104)the Research Program of Zhejiang Province.
文摘A doubled haploid （DH） population, which consists of 120 lines derived from anther culture of a typical indica and japonica hybrid‘CJ06＇/‘TNI＇, was used in this study. Ligule lengths of flag leaf were investigated for quantitative trait loci （QTL） mapping using the DH population. Five QTLs （qLL-2, qLL.4, qLL-6, qLL-IO and qLL-12） controlling the ligule length （LL） were detected on chromosomes 2, 4, 6, 10 and 12, with the variances explained 11.4%, 13.6%, 27.8%, 22.1% and 11.0%, respectively. Using four known genes of ZmGL1, ZmGL2, ZmGL3 and ZmGL4 in maize from the MaizeGDB, their homologs in rice were aligned and integrated into the existing simple sequence repeats linkage map by in silico mapping. A ZmLG1 homolog gene, OsLG1 encoding a squamosa promoter binding protein, was located between the markers RM255 and RM280, which is just identical to the interval of qLL.4 on the long arm of chromosome 4. The results are beneficial to dissection of the ligule molecular mechanism and the study of cereal evolution.
基金Supported by Department of Biotechnology,Ministry of Science and Technology,New Delhi,Government of India vide BT/PR8348/MED/30/1023/2013 to Paul JPURSE grant from the Department of Science and Technology,New Delhi India vide 6(54)SLS/JP/DST PURSE/2015-2016
文摘To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients. METHODSColonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted. RESULTSThe miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC. CONCLUSIONThe present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.
文摘There are many studies on enzymatic pathways of anthocyanin biosynthesis, but little is known about the anthocyanins transport in Oryze sativa. In silico analysis, the OsMRP15 (LOC_Os06g06440), an orthologous gene of mazie anthocyanin transporter ZmMRP3, has been identified in rice. The OsMRP15 contained a 4425bp open reading frame (ORF) encoding a 1475 amino acid protein, belonging to a MRP subfamily of ABC transporters, and has a high sequence identity, very similar protein structure, and the same arrangement of domains to ZmMRP3, but the genomic structure of OsMRP15 was significant difference with ZmMRP3. The prediction promoter of OsMRP15 has many presumed anthocyanin regulatory sites. The phylogenetic analysis of MRPs in rice, mazie and Arabidopsis showed that OsMRP15 and ZmMRP3 belonged to the same subbranch. The expression pattern indicated that OsMRP15 was co-expression with two anthocyanin transcription factors. These analysis results implied that as an ortholog of ZmMRP3, the function of OsMRP15 was possibly as a membrane-bound transporter required for vacuolar uptake of anthocyanins in rice.
基金supported by grants from the National Basic Research Program of China (2006CB708208,2006CB101901)the Program for Changjiang Scholars and Innovative Research Team in University, Ministry of Education of China (IRT0558)+1 种基金the National Natural Science Foundation of China (30930064)the 111Project from the Ministry of Education of China(B07049)
文摘Pathogenesis-related proteins （PRs） play many important roles in plant defense response against pathogen attack. To better understand the molecular mechanism of PR genes involved in wheat adult plant resistance （APR） to stripe rust, based on a differentially expressed transcribed derived fragment （TDF）, a novel PR gene from wheat cv. Xingzi 9104 infected by the Puccinia striiformis Westend f. sp. tritici Erikss. pathotype CY32, which was highly similar to the maize ZmPRIO gene and designated as TaPRIO, was identified using in silico cloning and RT-PCR method. This novel TaPRIO gene was predicted to encode a 160-amino acid protein with a deduced molecular weight of 17.06 kDa and an isoelectronic point （pI） of 5.19. An amino acid sequence analysis of TaPR10 demonstrated the presence of a typical conserved domain of pathogenesis related protein Bet v I family. Multiple alignment analysis based on the amino acids encoded by 10 different PRIO genes from maize （Zea mays）, rice （Oryza sativa）, broomcorn （Sorghum bicolor）, and wheat （Triticum aestivum） indicated that PR proteins of class 10 was conserved among the 4 plant species with about 80% similarity. DNA sequence of TaPRIO suggested the presence of one 84-bp intron with the splicing sites of GT-AT bi-nucleotide sequence between 188 and 271 bp. Using a real-time quantitative RT-PCR （qRT-PCR）, expression profiles of TaPRIO revealed that at the adult-plant stage, TaPRIO transcript was up-regulated as early as 12 h post-inoculation （hpi）, with the occurrence of maximum induction at 24 hpi. At the seedling stage, TaPRIO was also slightly induced 18 hpi. However, the transcript amount was relatively lower than that of the adult-plant stage. Taken together, these results suggest that TaPRIO may participate in wheat defense response of APR to stripe rust.
基金supported by Science and Technology Commission of Shanghai Municipality(Nos.19430741400 and 19410761200,China)National Natural Science Foundation of China(Nos.81973247 and 81703434)
文摘Lipid-based formulations(LBFs)have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.However,construction of in vitro and in vivo correlations(IVIVCs)for LBFs is quite challenging,owing to a complex in vivo processing of these formulations.In this paper,we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption;based on the concept of IVIVCs,the current status of in vitro models to establish IVIVCs for LBFs is reviewed,while future perspectives in this field are discussed.In vitro tests,which facilitate the understanding and prediction of the in vivo performance of solid dosage forms,frequently fail to mimic the in vivo processing of LBFs,leading to inconsistent results.In vitro digestion models,which more closely simulate gastrointestinal physiology,are a more promising option.Despite some successes in IVIVC modeling,the accuracy and consistency of these models are yet to be validated,particularly for human data.A reliable IVIVC model can not only reduce the risk,time,and cost of formulation development but can also contribute to the formulation design and optimization,thus promoting the clinical translation of LBFs.
基金supported by The National Natural Science Funds of China(No.31901635).
文摘This study aimed to identify novel ACEI peptides from Larimichthys crocea titin using in silico approaches and to clarify the molecular interaction mechanism.The hydrolyzed peptides of titin were compared with known ACEI peptides in the AHTPDB and BIOPEP-UWM database.Furthermore,peptides were evaluated for their solubility,ADMET properties,ΔG(kcal/mol)values,and in vitro ACEI activity.Molecular mechanism of ACE-peptide was performed by molecular interactions and binding orientation study.The results revealed that IC50 values of Trp-Ala-Arg(WAR)and Trp-Gln-Arg(WQR)were(31.2±0.8)and(231.33±0.02)mol/L,respectively.The docking interactions result suggested that ACE-WAR and ACEWQR complexes have same binding site,including the residues LYS511,TYR520,TYR523,HIS353,and HIS513.Molecular docking of two tripeptides WAR and WQR with ACE studies predicted their binding site and clarified the interaction between ACE and its inhibitors.The molecular docking data are consistent with the ACE inhibitory activity of the studied peptides.The results showed that Larimichthys crocea titin may be a valuable source for developing nutraceutical food.
基金supported by research grants from the Special Funds for Major State Basic Research of China(Grant G1999053905)
文摘Human fibrinogen-related protein-1/liver fibrinogen-related protein-1 (HFREP-l/LFIRE-1), a liver-specific protein, is a member of fibrinogen superfamily that exerts various biological activities. However, the function of HFREP-l/LFIRE-1 in liver remains unknown. Here we isolated its mouse ortholog gene-mouse fibrinogen-related protein-1 (mfrep-1), which encoded 314 amino acids, exhibiting 80.4% similarity to HFREP-l/LFIRE-1. Northern blot analysis revealed that 1.2-kb mfrep-1 mRNA was detected selectively in mouse liver. To explore the function of MFREP-1, we examined the levels of mfrep-1 mRNA during regeneration after 70% partial hepatectomy (PHx) in mice, mfrep-1 mRNA increased in the regenerating liver and reached the first shoulder peak at 2-4 h after PHx. Cycloheximide pretreatment could suppress the induction of mfrep-1, indicating the up-regulation of this gene need de novo protein synthesis. Its mRNA continued to elevate at 6 h thereafter and reached the second peak at 24 h. The enhanced expression of mfrep-1 maintained high until 72 h and then declined slowly to the basal level. Immunohistochemistry assessment confirmed the up-regulated expression of MFREP-1 protein in parenchymal cells during liver regeneration. These data suggested that MFREP-1 might play an important role in liver regeneration and be involved in the regulation of cell growth.
基金Supported by the National Natural Science Foundation of China(No.81403268 and No.81403114)the Public Welfare Technology Application Research Linkage Project of Anhui Province(No.1704f0704062)+1 种基金the Talent Fund of Anhui Science and Technology University(No.SPWD201602)Education Department of Anhui Province(No.gxfx2017076)
文摘Objective： To elucidate the action mechanism of Xingnaojing Injection （醒脑静注射液, XNJI） for sepsis, and to target screen the potential bioactive ingredients. Methods： An integrated protocol that combines in silico target screen （molecular docking） and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target （C-T） interaction network. The XNJI＇s bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-1ipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction. Results： Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment. Conclusions： The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.
文摘Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.
文摘Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, HMPREF3221_01179, derived from F. nucleatum strain MJR7757B, employing various computational methods to anticipate both its structure and functional characteristics. NCBI conserved domain analysis, NCBI BLASTp and MEGA Phylogenetic tree study characterize the target protein as an outer membrane efflux protein (ToIC family) which facilitate the bacterial transmembrane transport. With a molecular weight of 52120.02 Da, an isoelectric point (pI) of 8.33, and an instability index of 29.47, the protein is anticipated to exhibit good solubility in the extracellular space and crucial stability for pharmaceutical applications. The protein’s structure meets quality standards during the construction and refinement of its 3D model. The efflux inhibitor Arginine beta-naphthylamide exhibits a significant binding affinity (-7.1 kcal/mol) to the binding site of the target protein. The in-silico analysis improves the understanding of the protein and facilitates future investigations into therapeutic medication.
文摘Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study leverages computational tools to dissect the differential gene expression profiles in retinoblastoma. Methods: Employing an in silico approach, we analyzed gene expression data from public repositories by applying rigorous statistical models, including limma and de seq 2, for identifying differentially expressed genes DEGs. Our findings were validated through cross-referencing with independent datasets and existing literature. We further employed functional annotation and pathway analysis to elucidate the biological significance of these DEGs. Results: Our computational analysis confirmed the dysregulation of key retinoblastoma-associated genes. In comparison to normal retinal tissue, RB1 exhibited a 2.5-fold increase in expression (adjusted p Conclusions: Our analysis reinforces the critical genetic alterations known in retinoblastoma and unveils new avenues for research into the disease’s molecular basis. The discovery of chemoresistance markers and immune-related genes opens potential pathways for personalized treatment strategies. The study’s outcomes emphasize the power of in silico analyses in unraveling complex cancer genomics.
基金The work in XGZ＇s lab is supported by CAS strategic leading project on designer breeding by molecular module （No. XDA08020301）, the National High Technology Development Plan of the Ministry of Science and Technology of China （2014AA101601）, the National Natural Science Foundation of China （No. C020401）, the National Key Basic Research Program of China （No. 2015CB150104）, Bill and Melinda Gates Foundation （No. OPP1060461）, CAS-CSIRO Cooperative Research Program （No. GJHZ1501）.
文摘Background： The increase in global population, climate change and stagnancy in crop yield on unit land area basis in recent decades urgently call for a new approach to support contemporary crop improvements, ePlant is a mathematical model of plant growth and development with a high level of mechanistic details to meet this challenge. Results： ePlant integrates modules developed for processes occurring at drastically different temporal （10-8-106 seconds） and spatial （10-10-10 meters） scales, incorporating diverse physical, biophysical and biochemical processes including gene regulation, metabolic reaction, substrate transport and diffusion, energy absorption, transfer and conversion, organ morphogenesis, plant environment interaction, etc. Individual modules are developed using a divide-and-conquer approach; modules at different temporal and spatial scales are integrated through transfer variables. We further propose a supervised learning procedure based on information geometry to combine model and data for both knowledge discovery and model extension or advances. We finally discuss the recent formation of a global consortium, which includes experts in plant biology, computer science, statistics, agronomy, phenomics, etc. aiming to expedite the development and application of ePlant or its equivalents by promoting a new model development paradigm where models are developed as a community effort instead of driven mainly by individual labs＇ effort. Conclusions： ePlant, as a major research tool to support quantitative and predictive plant science research, will play a crucial role in the future model guided crop engineering, breeding and agronomy.
文摘The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR and mass spectroscopy. These new compounds were tested for their antiproliferative activities on seven representative human tumoral cell lines (Huh7 D12, Caco2, MDA-MB231, MDA-MB468, HCT116, PC3 and MCF7) and also on fibroblasts. Among them, only the compounds 6c showed micromolar cytotoxic activity on tumor cell lines (1.8 50 50 > 25 μM). Finally, in silico ADMET studies ware performed to investigate the possibility of using of the identified compound 6c as potential anti-tumor compound.
文摘Background: Cosmetic formulations, and particularly solar products which contain mineral and chemical UV-filters, are often suspected of causing harmful effects on marine fauna and flora. After the publication of our work in 2019 concerning the ecotoxicological effects of such formulations on corals (Seriatopora hystrix), we here provide some new information about the biodegradability and the ecotoxicological effects of these products on marine zoo- and phytoplankton. Therefore, we choose to realize in silico and in vitro studies of the biodegradability of several solar products but also to evaluate the ecotoxicological effects of these products on one phytoplankton, i.e. Phaeodactylum tricornutum, and one zooplankton, i.e. Acartia tonsa, of a great importance for sea species survival (notably as sources of food). Materials and methods: Two different approaches were used to study the biodegradability of the tested products: One in silico method and an in vitro one. 2 solar products were involved in the in silico study which consisted in the determination of the degradation factor (DF) of each ingredient of the tested formulas in order to finally obtain their estimated biodegradability percentage. Already available data concerning each ingredient coupled to a computer model developed with one of our partners were used to achieve this study. The in vitro study involved 8 formulas containing UV-filters and was led by following the OECD 301 F guidelines. Ecotoxicological studies of 7 of the formulas containing UV-filters were for their part realized by following the ISO 10253 guidelines for the experiments led with Phaeodactylum tricornutum, and the ISO 14669 guidelines for the experiments led with Acartia tonsa. In these studies, the effect of each tested product on crustaceans’ mortality and algal growth inhibition was assessed. Results: The in silico study predicted that formulas containing chemical UV-filters display a high biodegradability (superior to the threshold value of 60% given by the OECD 301 F guideli
