Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).Ho...Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).展开更多
Prevalence and importance of polymorphism occurring in pharmaceutical compounds are well recognized.It is of great importance to prepare and select the right form from the beginning during drug discovery and developme...Prevalence and importance of polymorphism occurring in pharmaceutical compounds are well recognized.It is of great importance to prepare and select the right form from the beginning during drug discovery and development.This review introduces the basic concepts of“What is polymorphism?”,addresses a fundamental question of“Why do polymorphs form?”,and provides practical guidelines of“How to prepare polymorphs?”“How to evaluate the relative thermodynamic stability between polymorphs?”,and“How to analyze polymorphs?”.Moreover,case studies of pharmaceutically important polymorphs are provided.展开更多
The rapidly evolving environment of assisted reproductive technology(ART)requires consideration of how new innovations are reshaping clinical practice as much as research.In particular,there are three key areas that,w...The rapidly evolving environment of assisted reproductive technology(ART)requires consideration of how new innovations are reshaping clinical practice as much as research.In particular,there are three key areas that,while full of promise,also present significant challenges:the use of artificial intelligence(AI)in embryo selection,the impact of personalized medicine on ART success rates,and the ethical considerations of genetic screening of embryos[1].This letter is meant to provoke further discussion and highlight the need for harmonized global guidelines as these advances continue to reshape the reproductive medicine environment.展开更多
There are two fundamental goals in statistical learning： identifying relevant predictors and ensuring high prediction accuracy. The first goal, by means of variable selection, is of particular importance when the tru...There are two fundamental goals in statistical learning： identifying relevant predictors and ensuring high prediction accuracy. The first goal, by means of variable selection, is of particular importance when the true underlying model has a sparse representation. Discovering relevant predictors can enhance the performance of the prediction for the fitted model. Usually an estimate is considered desirable if it is consistent in terms of both coefficient estimate and variable selection. Hence, before we try to estimate the regression coefficients β , it is preferable that we have a set of useful predictors m hand. The emphasis of our task in this paper is to propose a method, in the aim of identifying relevant predictors to ensure screening consistency in variable selection. The primary interest is on Orthogonal Matching Pursuit（OMP）.展开更多
The aim of this experimental work is to select wheat progenies tolerant high levels of salinity. Studies were conducted to determine the realized response in salt tolerance of some selected progeny （F3） through one ...The aim of this experimental work is to select wheat progenies tolerant high levels of salinity. Studies were conducted to determine the realized response in salt tolerance of some selected progeny （F3） through one cycle of screening and selection and the extent of variability for salt tolerance among selected progeny （F3） of wheat. All the selected progeny （F3） derived from （F2） populations after exposure are to high salinity level, were tested for salt tolerance during all growth stages in sand cultures salinized with 0, 100, 175 mM NaCI as compared with the unselected progeny （F2）. Results showed that the selected progeny （F3） were in all cases except one, superior in yield at maturity and in most cases significantly so, both at 100 and 175 mM NaCl, to the yield of the unselected progeny （F2） controls. In this study, some selected progeny exhibited more than twice the seed yield compared with that obtained from unselected progeny at 175 mM NaCl, and their seed yield was also significantly higher than that at 0 mM NaCl. Results also indicated that the highest value percentage of realized response in salt tolerance was in （F3AS1） and （F3AS2） at 175 mM NaCI. It is important to bear in mind that the significant improvement in selected progeny was achieved just in a single cycle of selection. There is then a strong possibility that further increases in tolerance may be obtained through further cycles of selection till reaching F6 or F7 where would show genetics stability.展开更多
Wolman disease is a rare autosomal recessive disorder caused by mutations in the LIPA gene (10q23.31). The LIPA gene encodes lysosomal acid lipase (LAL), which plays a key role in hydrolysis of the cholesteryl esters ...Wolman disease is a rare autosomal recessive disorder caused by mutations in the LIPA gene (10q23.31). The LIPA gene encodes lysosomal acid lipase (LAL), which plays a key role in hydrolysis of the cholesteryl esters and triglycerides. Two unrelated families from Bulgaria were referred for genetic testing with clinical diagnosis Wolman disease. Sanger sequencing of all coding exons and exon-intron boundaries of the LIPA gene was performed. The index patients were found to be homozygous for two different mutations in the LIPA gene: a missense mutation, c.260G > T, p.Gly87Val, which affects the enzyme active site and a splice-site change, c.822+1G > A, which most probably destroys the enzyme polypeptide chain. These two completely different types of mutations along the LIPA gene resulted in a very similar phenotype involving liver, kidney, gastrointestinal, muscle and blood disturbances. As consanguinity is not typical for the Bulgarian population, a possible explanation of the homozygosity could be presence of endemic regions for given mutations. To check this hypothesis, selective screening for these mutations was performed in two presumable endemic regions in Bulgaria. Altogether, 100 newborns were screened for p.Gly87Val mutation and the detected carrier frequency was about 1% (1/100), while in the group of 100 newborns screened for the c.822 + 1G > A mutation the detected carrier frequency was 2% (2/100). The results indicate a high recurrence risk of Wolman disease in these particular Bulgarian regions of about 1:10000. These findings are from crucial importance for the inhabitants of the corresponding parts of Bulgaria. They may benefit from early genetic testing and adequate genetic counselling during family planning.展开更多
Background: Colonization with methicillin-resistant Staphylococcus aureus(MRSA) poses a hygiene risk that does not spare field hospitals or military medical field camps during military deployments. Diagnostic options ...Background: Colonization with methicillin-resistant Staphylococcus aureus(MRSA) poses a hygiene risk that does not spare field hospitals or military medical field camps during military deployments. Diagnostic options for unambiguously identifying MRSA isolates are usually scarce in military environments. In this study, we assessed the stepwise application of two different selective agars for the specific identification of MRSA in screening analyses.Methods: Nasal swabs from 1,541 volunteers were subjected to thioglycollate broth enrichment and subsequently screened on CHROMagar MRSA selective agar for the identification of MRSA. The MRSA identity of suspiciouslooking colonies was confirmed afterwards or excluded by another selective agar, chrom ID MRSA. All isolates from the selective agars with MRSA-specific colony morphology were identified by biochemical methods and mass spectrometry.Results: The initial CHROMagar MRSA screening identified suspicious colonies in 36 out of 1541 samples. A total of 25 of these 36 isolates showed MRSA-like growth on chrom ID agar. Out of these 25 isolates, 24 were confirmed as MRSA, while one isolate was identified as Staphylococcus kloosii. From the 11 strains that did not show suspicious growth on chrom ID agar, 3 were methicillin-sensitive Staphylococcus aureus(MSSA, with one instance of cocolonization with Corynebacterium spp.), 2 were confirmed as MRSA(with 1 instance of co-colonization with MSSA), 2 were lost during passaging and could not be re-cultured, one could not be identified by the applied approaches, and the remaining 3 strains were identified as Staphylococcus saprophyticus, Staphylococcus hominis(co-colonized with Macrococcus caseolyticus) and Staphylococcus cohnii, respectively.Conclusion: The application of the selective agar CHROMagar MRSA alone proved to be too non-specific to allow for a reliable diagnosis of the presence of MRSA. The combined use of two selective agars in a stepwise approach reduced this non-specificity with an acceptably low loss of sensitivity. Accordingly, such a stepwise screening approach might be an option for resource-restricted military medical field camps.展开更多
Understanding the performance of new crop genotypes for traits of relevance is important in selecting potential cultivars to satisfy end-users. The objective of this study was to determine the performance of new banan...Understanding the performance of new crop genotypes for traits of relevance is important in selecting potential cultivars to satisfy end-users. The objective of this study was to determine the performance of new banana genotypes for bunch mass (BMS) and BMS-related traits, resistance to black Sigatoka and sensory attributes. Eight cooking banana genotypes consisting of six new hybrid genotypes selected from advanced breeding trials and two control cultivars were evaluated in a randomized complete block design for three crop cycles at three locations in Uganda. Genotype, location, crop cycle and their interaction effects were significantly different for most traits assessed. The overall top two genotypes (“9058K-2” and “8099K-16”) combining high BMS, resistance to black Sigatoka and acceptable sensory attributes were identified. These genotypes are suggested as potential commercial cultivars for release to farmers in Uganda and/or other East African countries with similar environmental conditions to those where the genotypes were tested. It should be noted that high BMS/yield and resistance to diseases are not the only factors to consider when selecting banana genotypes that meet end-user needs. A combination of high BMS/yield, acceptable sensory attributes and resistance to diseases essentially influence the selection process of banana cultivars.展开更多
Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor ...Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC_(50)=5.41 nM)than that of tubastatin A(TubA)(IC_(50)=15.11 nM),along with a favorable subtype selectivity profile(selectivity index z 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC_(50)=2.59 mM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.展开更多
A thick-screen frequency selective surface （FSS） has not only a broad bandwidth but also the advantages of overcoming the multilayer FSS shortcoming of complex structure and low transmittance of centre frequency due...A thick-screen frequency selective surface （FSS） has not only a broad bandwidth but also the advantages of overcoming the multilayer FSS shortcoming of complex structure and low transmittance of centre frequency due to the cascade of FSSs, and this means it could potentially be applied in a stealth curved streamlined radome. However, there is an unsteadiness of centre frequency in a wide range of incident angles and another unsteadiness of polarization in a big incident angle. In order to solve these problems, in this paper we provide a novel four-legged loaded element thick-screen FSS. The structure is analysed and simulated using the mode matching method and moment method. The centre frequency, the transmittance of centre frequency, and bandwidth of the structure are investigated when some parameters including the polarization at a big incident angle and the incident angles of TE ＆： TM waves are changed. The novel four-legged loaded element thick-screen FSS has better transmission properties with a better steadiness of polarization and incident angle independence. The novel structure of the four-legged loaded element thick-screen FSS provides a valuable reference for their application in a stealth curved streamlined radome.展开更多
Directed evolution is a powerful engineering technique that mimics natural selection in the laboratory to create biomolecules with enhanced or novel properties.A typical directed evolution system involves the generati...Directed evolution is a powerful engineering technique that mimics natural selection in the laboratory to create biomolecules with enhanced or novel properties.A typical directed evolution system involves the generation of a large library of diversified variants through mutagenesis of an initial sequence,screening or selection of variants with improved or desirable properties,and repeat of the cycle with the best hits to accumulate beneficial mutations(Zeymer and Hilvert,2018).展开更多
目的评估双源CT Sn 100kVp能谱纯化用于低剂量肺结节筛查的诊断效能。方法纳入2020年4月至2023年12月期间在南京医科大学附二院接受至少两次低剂量CT检查的100名肺结节患者,将初检患者纳入常规电压组[(以110 kVp、52 mAs行常规电压低剂...目的评估双源CT Sn 100kVp能谱纯化用于低剂量肺结节筛查的诊断效能。方法纳入2020年4月至2023年12月期间在南京医科大学附二院接受至少两次低剂量CT检查的100名肺结节患者,将初检患者纳入常规电压组[(以110 kVp、52 mAs行常规电压低剂量螺旋CT(LDCT)扫描)],复检患者纳入低电压组(以Sn 100kVp、70 mAs行低电压能谱纯化低剂量双源CT扫描),比较两组辐射剂量、客观图像质量评价、主观图像质量评分及诊断效能。结果低电压组的容积CT剂量指数(CTDIvol)、剂量长度乘积(DLP)和有效辐射剂量(ED)均显著低于常规电压组(P均<0.05)。低电压组肺窗标准差(SD)低于常规电压组,肺窗对比噪声比(CNR)高于常规电压组(P均<0.05)。低电压组肺窗、纵隔窗主观图像质量评分低于常规电压组(P均<0.05)。与病理结果相比,常规电压LDCT检测肺结节的Kappa指数为0.944,双源CT Sn 100kVp检测肺结节的Kappa指数为0.917,均与病理结果一致性良好。结论本研究表明,双源CT Sn 100kVp能谱纯化技术在低剂量肺结节筛查中展现出良好的诊断效能,同时显著降低了辐射剂量,为临床提供了一种更为安全有效的筛查方法。展开更多
Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via trans...Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompt-ing increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.展开更多
Waterlogging strongly affects agronomic performance of maize(Zea mays L.).In order to investigate the suitable selection criteria of waterflooding tolerant genotypes,and identify the most susceptible stage and the bes...Waterlogging strongly affects agronomic performance of maize(Zea mays L.).In order to investigate the suitable selection criteria of waterflooding tolerant genotypes,and identify the most susceptible stage and the best continuous treatment time to waterlogging,20 common maize inbred lines were subjected to successive artificial waterflooding at seedling stage,and waterlogging tolerance coefficient(WTC)was used to screen waterflooding tolerant genotypes.In addition,peroxidase(POD)activities and malondialdehyde(MDA)contents were measured for 6 of 20 lines.The results showed that the second leaf stage(V2)was the most susceptible stage,and 6 d after waterflooding was the best continuous treatment time.Dry weight(DW)of both shoots and roots of all lines were significantly reduced at 6 d time-point of waterlogging,compared to control.POD activities and MDA contents were negatively and significantly correlated,and the correlation coefficient was-0.9686(P〈0.0001).According to the results,WTC of shoot DW can be used for practical screening as a suitable index,which is significantly different from control and waterlogged plants happened 6 d earlier.Furthermore,leaf chlorosis,MDA content and POD activities could also be used as reference index for material screening.The implications of the results for waterlogging-tolerant material screening and waterlogging-tolerant breeding have been discussed in maize.展开更多
Frequency selective surfaces (FSSs) have been successfully used in constructing microwave absorbers which demonstrate the ability of modifying and improving its absorbing performances. In this paper, microwave absorbe...Frequency selective surfaces (FSSs) have been successfully used in constructing microwave absorbers which demonstrate the ability of modifying and improving its absorbing performances. In this paper, microwave absorber based on ferromagnetic nano-films has been proposed and investigated with a structure similar to that of the Salisbury screen except that the resistive sheet is replaced by FSS of square patch array of the nano-film. We have explored the FSS absorber from three aspects: equivalent circuit model, electromagnetic full-wave simulation and the actual sample measurement. By carefully tuning the patch size, the thickness of the dielectric spacer and the specification of the ferromagnetic nano-film, we obtain the optimized performance of broadband microwave absorbing. Due to the light weight of the nano-films, the proposed absorbers can achieve an ultra-low surface density less than 0.25 kg/m2.展开更多
OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric disorders.Currently available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncerta...OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric disorders.Currently available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncertainty as to the roles each DR subtype plays physiologically.Our lab employed high throughput screening paradigms to discover highly selective modulators for the DRD3.METHODS The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove Rx Path Hunter?β-arrestin assay for compounds that activate the DRD3 without effects on the DRD2.Confirmation and counter-screens assessed selectivity and mechanisms of action.We identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAR) study to increase potency while maintaining selectivity.The lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BRET)-based β-arrestin recruitment and G-protein activation assays as well as p-ERK assays.Potential neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell model.RESULTS ML417 displays potent,DRD3-selective agonist activity in multiple functional assays.Binding and functional GPCR screens(>165 receptors) show ML417 has limited cross-reactivity with other GPCRs.ML417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell model.CONCLUSION We have discovered and characterized ML417,a potent and highly selective DRD3 agonist.This compound will be useful as a research tool,and may prove useful as a therapeutic drug lead.展开更多
基金supported by the Jilin Science and Technology Development Program,China (20240602032RC)the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZD001)+1 种基金the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZY012)the Jilin Province Development and Reform Commission-Project for Improving the Independent Innovation Capacity of Major Grain Crops,China (2024C002)。
文摘Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).
基金This research was supported by a grant(14172MFDS189)from Ministry of Food and Drug Safety in 2014Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(2014R1A1A1006429).
文摘Prevalence and importance of polymorphism occurring in pharmaceutical compounds are well recognized.It is of great importance to prepare and select the right form from the beginning during drug discovery and development.This review introduces the basic concepts of“What is polymorphism?”,addresses a fundamental question of“Why do polymorphs form?”,and provides practical guidelines of“How to prepare polymorphs?”“How to evaluate the relative thermodynamic stability between polymorphs?”,and“How to analyze polymorphs?”.Moreover,case studies of pharmaceutically important polymorphs are provided.
文摘The rapidly evolving environment of assisted reproductive technology(ART)requires consideration of how new innovations are reshaping clinical practice as much as research.In particular,there are three key areas that,while full of promise,also present significant challenges:the use of artificial intelligence(AI)in embryo selection,the impact of personalized medicine on ART success rates,and the ethical considerations of genetic screening of embryos[1].This letter is meant to provoke further discussion and highlight the need for harmonized global guidelines as these advances continue to reshape the reproductive medicine environment.
文摘There are two fundamental goals in statistical learning： identifying relevant predictors and ensuring high prediction accuracy. The first goal, by means of variable selection, is of particular importance when the true underlying model has a sparse representation. Discovering relevant predictors can enhance the performance of the prediction for the fitted model. Usually an estimate is considered desirable if it is consistent in terms of both coefficient estimate and variable selection. Hence, before we try to estimate the regression coefficients β , it is preferable that we have a set of useful predictors m hand. The emphasis of our task in this paper is to propose a method, in the aim of identifying relevant predictors to ensure screening consistency in variable selection. The primary interest is on Orthogonal Matching Pursuit（OMP）.
文摘The aim of this experimental work is to select wheat progenies tolerant high levels of salinity. Studies were conducted to determine the realized response in salt tolerance of some selected progeny （F3） through one cycle of screening and selection and the extent of variability for salt tolerance among selected progeny （F3） of wheat. All the selected progeny （F3） derived from （F2） populations after exposure are to high salinity level, were tested for salt tolerance during all growth stages in sand cultures salinized with 0, 100, 175 mM NaCI as compared with the unselected progeny （F2）. Results showed that the selected progeny （F3） were in all cases except one, superior in yield at maturity and in most cases significantly so, both at 100 and 175 mM NaCl, to the yield of the unselected progeny （F2） controls. In this study, some selected progeny exhibited more than twice the seed yield compared with that obtained from unselected progeny at 175 mM NaCl, and their seed yield was also significantly higher than that at 0 mM NaCl. Results also indicated that the highest value percentage of realized response in salt tolerance was in （F3AS1） and （F3AS2） at 175 mM NaCI. It is important to bear in mind that the significant improvement in selected progeny was achieved just in a single cycle of selection. There is then a strong possibility that further increases in tolerance may be obtained through further cycles of selection till reaching F6 or F7 where would show genetics stability.
文摘Wolman disease is a rare autosomal recessive disorder caused by mutations in the LIPA gene (10q23.31). The LIPA gene encodes lysosomal acid lipase (LAL), which plays a key role in hydrolysis of the cholesteryl esters and triglycerides. Two unrelated families from Bulgaria were referred for genetic testing with clinical diagnosis Wolman disease. Sanger sequencing of all coding exons and exon-intron boundaries of the LIPA gene was performed. The index patients were found to be homozygous for two different mutations in the LIPA gene: a missense mutation, c.260G > T, p.Gly87Val, which affects the enzyme active site and a splice-site change, c.822+1G > A, which most probably destroys the enzyme polypeptide chain. These two completely different types of mutations along the LIPA gene resulted in a very similar phenotype involving liver, kidney, gastrointestinal, muscle and blood disturbances. As consanguinity is not typical for the Bulgarian population, a possible explanation of the homozygosity could be presence of endemic regions for given mutations. To check this hypothesis, selective screening for these mutations was performed in two presumable endemic regions in Bulgaria. Altogether, 100 newborns were screened for p.Gly87Val mutation and the detected carrier frequency was about 1% (1/100), while in the group of 100 newborns screened for the c.822 + 1G > A mutation the detected carrier frequency was 2% (2/100). The results indicate a high recurrence risk of Wolman disease in these particular Bulgarian regions of about 1:10000. These findings are from crucial importance for the inhabitants of the corresponding parts of Bulgaria. They may benefit from early genetic testing and adequate genetic counselling during family planning.
文摘Background: Colonization with methicillin-resistant Staphylococcus aureus(MRSA) poses a hygiene risk that does not spare field hospitals or military medical field camps during military deployments. Diagnostic options for unambiguously identifying MRSA isolates are usually scarce in military environments. In this study, we assessed the stepwise application of two different selective agars for the specific identification of MRSA in screening analyses.Methods: Nasal swabs from 1,541 volunteers were subjected to thioglycollate broth enrichment and subsequently screened on CHROMagar MRSA selective agar for the identification of MRSA. The MRSA identity of suspiciouslooking colonies was confirmed afterwards or excluded by another selective agar, chrom ID MRSA. All isolates from the selective agars with MRSA-specific colony morphology were identified by biochemical methods and mass spectrometry.Results: The initial CHROMagar MRSA screening identified suspicious colonies in 36 out of 1541 samples. A total of 25 of these 36 isolates showed MRSA-like growth on chrom ID agar. Out of these 25 isolates, 24 were confirmed as MRSA, while one isolate was identified as Staphylococcus kloosii. From the 11 strains that did not show suspicious growth on chrom ID agar, 3 were methicillin-sensitive Staphylococcus aureus(MSSA, with one instance of cocolonization with Corynebacterium spp.), 2 were confirmed as MRSA(with 1 instance of co-colonization with MSSA), 2 were lost during passaging and could not be re-cultured, one could not be identified by the applied approaches, and the remaining 3 strains were identified as Staphylococcus saprophyticus, Staphylococcus hominis(co-colonized with Macrococcus caseolyticus) and Staphylococcus cohnii, respectively.Conclusion: The application of the selective agar CHROMagar MRSA alone proved to be too non-specific to allow for a reliable diagnosis of the presence of MRSA. The combined use of two selective agars in a stepwise approach reduced this non-specificity with an acceptably low loss of sensitivity. Accordingly, such a stepwise screening approach might be an option for resource-restricted military medical field camps.
文摘Understanding the performance of new crop genotypes for traits of relevance is important in selecting potential cultivars to satisfy end-users. The objective of this study was to determine the performance of new banana genotypes for bunch mass (BMS) and BMS-related traits, resistance to black Sigatoka and sensory attributes. Eight cooking banana genotypes consisting of six new hybrid genotypes selected from advanced breeding trials and two control cultivars were evaluated in a randomized complete block design for three crop cycles at three locations in Uganda. Genotype, location, crop cycle and their interaction effects were significantly different for most traits assessed. The overall top two genotypes (“9058K-2” and “8099K-16”) combining high BMS, resistance to black Sigatoka and acceptable sensory attributes were identified. These genotypes are suggested as potential commercial cultivars for release to farmers in Uganda and/or other East African countries with similar environmental conditions to those where the genotypes were tested. It should be noted that high BMS/yield and resistance to diseases are not the only factors to consider when selecting banana genotypes that meet end-user needs. A combination of high BMS/yield, acceptable sensory attributes and resistance to diseases essentially influence the selection process of banana cultivars.
基金funded by Central Guidance on Local Science and Technology Development Fund of Hebei Province,China(Grant No.:226Z2605G)the Key Project from Hebei Provincial Department of Science and Technology,China(Grant No.:21372601D)+6 种基金Graduate Student Innovation Grant Program of Hebei Medical University,China(Grant No.:XCXZZB202303)Science Research Project of Hebei Education Department,China(Grant Nos.:BJ2025046,and CYZD202501)Program for Young Scientists in the Field of Natural Science of Hebei Medical University,China(Program Nos.:CYCZ2023010,CYCZ2023011,CYQD2021011,CYQD2021015 and CYQD2023012)Traditional Chinese Medicine Administration Project of Hebei Province,China(Project No.:2025427)National Natural Science Foundation of China(Grant No.:32100771)the Hebei Provincial Medical Science Research Project Plan,China(Project Nos.:20240241 and 20220200)Shijiazhuang Science and Technology Bureau,China(Grant Nos.:241200487A,and 07202204).
文摘Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC_(50)=5.41 nM)than that of tubastatin A(TubA)(IC_(50)=15.11 nM),along with a favorable subtype selectivity profile(selectivity index z 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC_(50)=2.59 mM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.
文摘A thick-screen frequency selective surface （FSS） has not only a broad bandwidth but also the advantages of overcoming the multilayer FSS shortcoming of complex structure and low transmittance of centre frequency due to the cascade of FSSs, and this means it could potentially be applied in a stealth curved streamlined radome. However, there is an unsteadiness of centre frequency in a wide range of incident angles and another unsteadiness of polarization in a big incident angle. In order to solve these problems, in this paper we provide a novel four-legged loaded element thick-screen FSS. The structure is analysed and simulated using the mode matching method and moment method. The centre frequency, the transmittance of centre frequency, and bandwidth of the structure are investigated when some parameters including the polarization at a big incident angle and the incident angles of TE ＆： TM waves are changed. The novel four-legged loaded element thick-screen FSS has better transmission properties with a better steadiness of polarization and incident angle independence. The novel structure of the four-legged loaded element thick-screen FSS provides a valuable reference for their application in a stealth curved streamlined radome.
基金supported by grants from the National Key Research&Development Program(2023YFD1400300)the National Science Foundation of China(32272518)the Central Public-Interest Scientific Institution Basal Research Fund of Chinese Academy of Agricultural Sciences(Y2025YC25).
文摘Directed evolution is a powerful engineering technique that mimics natural selection in the laboratory to create biomolecules with enhanced or novel properties.A typical directed evolution system involves the generation of a large library of diversified variants through mutagenesis of an initial sequence,screening or selection of variants with improved or desirable properties,and repeat of the cycle with the best hits to accumulate beneficial mutations(Zeymer and Hilvert,2018).
文摘目的评估双源CT Sn 100kVp能谱纯化用于低剂量肺结节筛查的诊断效能。方法纳入2020年4月至2023年12月期间在南京医科大学附二院接受至少两次低剂量CT检查的100名肺结节患者,将初检患者纳入常规电压组[(以110 kVp、52 mAs行常规电压低剂量螺旋CT(LDCT)扫描)],复检患者纳入低电压组(以Sn 100kVp、70 mAs行低电压能谱纯化低剂量双源CT扫描),比较两组辐射剂量、客观图像质量评价、主观图像质量评分及诊断效能。结果低电压组的容积CT剂量指数(CTDIvol)、剂量长度乘积(DLP)和有效辐射剂量(ED)均显著低于常规电压组(P均<0.05)。低电压组肺窗标准差(SD)低于常规电压组,肺窗对比噪声比(CNR)高于常规电压组(P均<0.05)。低电压组肺窗、纵隔窗主观图像质量评分低于常规电压组(P均<0.05)。与病理结果相比,常规电压LDCT检测肺结节的Kappa指数为0.944,双源CT Sn 100kVp检测肺结节的Kappa指数为0.917,均与病理结果一致性良好。结论本研究表明,双源CT Sn 100kVp能谱纯化技术在低剂量肺结节筛查中展现出良好的诊断效能,同时显著降低了辐射剂量,为临床提供了一种更为安全有效的筛查方法。
文摘Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompt-ing increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.
基金supported by the Natural Science Foundation of Hubei Province,China(2008CDB079)the National High Technology Research and Development Program of China(863 Program,2006AA100103)
文摘Waterlogging strongly affects agronomic performance of maize(Zea mays L.).In order to investigate the suitable selection criteria of waterflooding tolerant genotypes,and identify the most susceptible stage and the best continuous treatment time to waterlogging,20 common maize inbred lines were subjected to successive artificial waterflooding at seedling stage,and waterlogging tolerance coefficient(WTC)was used to screen waterflooding tolerant genotypes.In addition,peroxidase(POD)activities and malondialdehyde(MDA)contents were measured for 6 of 20 lines.The results showed that the second leaf stage(V2)was the most susceptible stage,and 6 d after waterflooding was the best continuous treatment time.Dry weight(DW)of both shoots and roots of all lines were significantly reduced at 6 d time-point of waterlogging,compared to control.POD activities and MDA contents were negatively and significantly correlated,and the correlation coefficient was-0.9686(P〈0.0001).According to the results,WTC of shoot DW can be used for practical screening as a suitable index,which is significantly different from control and waterlogged plants happened 6 d earlier.Furthermore,leaf chlorosis,MDA content and POD activities could also be used as reference index for material screening.The implications of the results for waterlogging-tolerant material screening and waterlogging-tolerant breeding have been discussed in maize.
文摘Frequency selective surfaces (FSSs) have been successfully used in constructing microwave absorbers which demonstrate the ability of modifying and improving its absorbing performances. In this paper, microwave absorber based on ferromagnetic nano-films has been proposed and investigated with a structure similar to that of the Salisbury screen except that the resistive sheet is replaced by FSS of square patch array of the nano-film. We have explored the FSS absorber from three aspects: equivalent circuit model, electromagnetic full-wave simulation and the actual sample measurement. By carefully tuning the patch size, the thickness of the dielectric spacer and the specification of the ferromagnetic nano-film, we obtain the optimized performance of broadband microwave absorbing. Due to the light weight of the nano-films, the proposed absorbers can achieve an ultra-low surface density less than 0.25 kg/m2.
基金supported by National Institute of Neurological Disorders and Stroke Intramural Research Program
文摘OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric disorders.Currently available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncertainty as to the roles each DR subtype plays physiologically.Our lab employed high throughput screening paradigms to discover highly selective modulators for the DRD3.METHODS The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove Rx Path Hunter?β-arrestin assay for compounds that activate the DRD3 without effects on the DRD2.Confirmation and counter-screens assessed selectivity and mechanisms of action.We identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAR) study to increase potency while maintaining selectivity.The lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BRET)-based β-arrestin recruitment and G-protein activation assays as well as p-ERK assays.Potential neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell model.RESULTS ML417 displays potent,DRD3-selective agonist activity in multiple functional assays.Binding and functional GPCR screens(>165 receptors) show ML417 has limited cross-reactivity with other GPCRs.ML417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell model.CONCLUSION We have discovered and characterized ML417,a potent and highly selective DRD3 agonist.This compound will be useful as a research tool,and may prove useful as a therapeutic drug lead.
