By means of mathematical modeling methods, we analyzed the relationship between the resistance to fluoroquinolones and GyrA mutation of Salmonella from animal isolates. We found that considering the influence of the r...By means of mathematical modeling methods, we analyzed the relationship between the resistance to fluoroquinolones and GyrA mutation of Salmonella from animal isolates. We found that considering the influence of the resistance to ciprofloxacin hydrochloride, enrofloxacin, ofloxacin, pefloacin mesylate and norfloxacin nicotinate of the five types of fluoroquinolones to GyrA mutation of animal Salmonella, the resistance of pefloacin mesylate had the most significant effect, while the resistance of ciprofloxacin hydrochloride and enrofloxacin were the least significant factors. Nearly half of the Salmonella supports such a rule that the MIC of norfloxacin nicotinate reaching 64 or 128 might lead to the mutation Ser83→Phe, MIC exceeding 512 might lead to the mutation Ser83→Gly; 60% of the sample supported that the MIC of enrofloxacin reaching 32 or 64 might lead to the mutation Asp87 →Asn. 80% of them agreed to the fact that the MIC of neither ciprofloxacin hydrochloride under 64 nor pefloacin mesylate below 512 might result in the gene mutation in 119 site. All Salmonella isolates supported the conclusion that the mutation Alal19→Val took place, if and only if the MIC of norfloxacin nicotinate exceeded 512.展开更多
Precise assessment of spinal cord cystic lesions is crucial to formulate effective therapeutic strategies,yet histological assessment of the lesion remains the primary method despite numerous studies showing inconsist...Precise assessment of spinal cord cystic lesions is crucial to formulate effective therapeutic strategies,yet histological assessment of the lesion remains the primary method despite numerous studies showing inconsistent results regarding estimation of lesion size via histology.On the other hand,despite numerous advances in micro-computed tomography(micro-CT)imaging and analysis that have allowed precise measurements of lesion size,there is not enough published data on its application to estimate intraspinal lesion size in laboratory animal models.This work attempts to show that micro-CT can be valuable for spinal cord injury research by demonstrating accurate estimation of syrinx size and compares between micro-CT and traditional histological analysis.We used a post-traumatic syringomyelia rat model to compare micro-CT analysis to conventional histological analysis.The study showed that micro-CT can detect lesions within the spinal cord very similar to histology.Importantly,micro-CT appears to provide more accurate estimates of the lesions with more measures(e.g.,surface area),can detect compounds within the cord,and can be done with the tissue of interest(spinal cord)intact.In summary,the experimental work presented here provides one of the first investigations of the use of micro-CT for estimating the size of intraparenchymal cysts and detecting materials within the spinal cord.All animal procedures were approved by the University of Akron Institutional Animal Care and Use Committee(IACUC)(protocol#LRE 16-05-09 approved on May 14,2016).展开更多
Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryo...Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryotic translation initiation factor (eIF)4E, its isoforms, eIF(iso)4E, and the cap-binding protein (CBP) in plants, have been implicated in viral infections aside from their importance in protein synthesis. Full-length cDNA encoding these putative eIF targets from susceptible/resistant and unknown hexaploid sweetpotato (Ipomoea batatas L. Lam) were amplified based on primers designed from the diploid wild-type relative Ipomoea trifida consensus sequences, and designated IbeIF4E, IbeIF(iso)4E and IbCBP. Comparative analyses following direct-sequencing of PCR-amplified cDNAs versus the cloned cDNA sequences identified multiple homeoalleles: one to four IbeIF4E, two to three IbeIF(iso)4E, and two IbCBP within all cultivars tested. Open reading frames were in the length of 696 bp IbeIF4E, 606 bp IbeIF(iso)4E, and 675 bp IbCBP. The encoded single polypeptide lengths were 232, 202, and 225 amino acids for IbeIF4E, IbeIF(iso)4E, and IbCBP, with a calculated protein molecular mass of 26 kDa, 22.8 kDa, and 25.8 kDa, while their theoretical isoelectric points were 5.1, 5.57, and 6.6, respectively. Although the homeoalleles had similar sequence lengths, single nucleotide polymorphisms and multi-allelic variations were detected within the coding sequences. The multi-sequence alignment performed revealed a 66.9% - 96.7% sequence similarity between the predicted amino acid sequences obtained from the homeoalleles and closely related species. Furthermore, phylogenetic analysis revealed ancestral relationships between the eIF4E homeoalleles and other species. The outcome herein on the eIF4E superfamily and its correlation in sequence variations suggest opportunities to decipher the role of eIF4E in hexaploid sweetpotato feathery mottle virus infection.展开更多
Several quinolino-benzoxaborole derivatives have been prepared to start from aminobenzoxaboroles. These derivatives have been evaluated for their anti-cancer activity on human and murine cancer cell lines and based on...Several quinolino-benzoxaborole derivatives have been prepared to start from aminobenzoxaboroles. These derivatives have been evaluated for their anti-cancer activity on human and murine cancer cell lines and based on their relative non-toxicity, these compounds were further evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis. The synthesized compounds were also evaluated for antifungal activity in C. albicans and C. neoformans.展开更多
Human pluripotent stem cells(hPSCs)can in theory give rise to any hematopoietic lineages,thereby offering opportunities for disease modeling,drug screening and cell therapies.However,gaps in our knowledge of the signa...Human pluripotent stem cells(hPSCs)can in theory give rise to any hematopoietic lineages,thereby offering opportunities for disease modeling,drug screening and cell therapies.However,gaps in our knowledge of the signaling requirements for the specification of human hematopoietic stem/progenitor cells(HSPCs),which lie at the apex of all hematopoietic lineages,greatly limit the potential of hPSC in hematological research and application.Transcriptomic analysis reveals aberrant regulation of WNT signaling during maturation of hPSC-derived hematopoietic progenitor cells(hPSC-HPCs),which results in higher mitochondria activity,misregulation of HOX genes,loss of self-renewal and precocious differentiation.These defects are partly due to the activation of the WNT target gene CDX2.Late-stage WNT inhibition improves the yield,self-renewal,multilineage differentiation,and transcriptional and metabolic profiles of hPSC-HPCs.Genome-wide mapping of transcription factor(TF)accessible chromatin reveals a significant overrepresentation of myeloid TF binding motifs in hPSC-HPCs,which could underlie their myeloid-biased lineage potential.Together our findings uncover a previously unappreciated dynamic requirement of the WNT signaling pathway during the specification of human HSPCs.Modulating the WNT pathway with small molecules normalizes the molecular differences between hPSC-HPCs and endogenous hematopoietic stem cells(HSCs),thereby representing a promising approach to improve the differentiation and function of hPSC-HPCs.展开更多
Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characteriza...Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characterization of genes that are critical for normal cell division and differentiation in Arabidopsis early anther development. We review here several recent studies on these genes, including the demonstration that the putative receptor protein kinases BAM1 and BAM2 together play essential roles in the control of early cell division and differentiation. In addition, we discuss the hypothesis that BAM1/2 may form a positive-negative feedback regulatory loop with a previously identified key regulator, SPOROCYTELESS （also called NOZZLE）, to control the balance between sporogenous and somatic cell types in the anther. Furthermore, we summarize the isolation and functional analysis of the DYSFUNCTIONAL TAPETUM1 （DYT1） gene in promoting proper tapetal cell differentiation. Our finding that DYT1 encodes a putative transcription factor of the bHLH family, as well as relevant expression analyses, strongly supports a model that DYT1 serves as a critical link between upstream factors and downstream target genes that are critical for normal tapetum development and function. These studies, together with other recently published works, indicate that cell-cell communication and transcriptional control are key processes essential for cell fate specification in anther development.展开更多
Microalgae are widely used in the pharmaceutical and energy industries,therefore the conditions for their cultivation and extraction methods play an important role in the profiling and acquisition of lipids.The effici...Microalgae are widely used in the pharmaceutical and energy industries,therefore the conditions for their cultivation and extraction methods play an important role in the profiling and acquisition of lipids.The efficiency of lipid extraction from microalgae has attracted great interest from industry because of the wide variety of lipids and amounts that can be obtained.Acutodesmus obliquus(Scenedesmus obliquus UTEX 393)was used in this study.It was cultivated in Bold 3N medium modified with 75%nitrogen at 25℃,pH 6.8,125 r/min and a photoperiod of 18/6 h and illuminated with white light provided by a Light-Emitting Diode Surface Mount Device extensions(LED SMD)with an intensity of 1200μE/(m^(2)·s).The cells were stained with the Red Nile(RN)technique to indicate lipid production.Four extraction methods were compared,classical,microwave(MW),Soxhlet,and ultrasound(US),using the same solvent proportions(hexane:chloroform:methanol=1:2:3).All samples were analyzed with Fourier Transform Infrared Spectroscopy(FTIR)and Gas Chromatography coupled to Mass Spectrometry(GC-MS).The results showed:1)lipid production detected by RN was consistent with microalgal growth;2)the MW technique was the best extraction method,according to the statistical analysis through Randomized Complete Block(RCB)design and performance of 4.6%;and 3)the presence of saturated and unsaturated acids was indicated by FTIR spectra.GC-MS was able to identify palmitic and linoleic acids as the likely major constituents of the sample.展开更多
Aging is characterized by progressive functional decline driven by stem cell exhaustion,chronic inflammation,and cellular senescence.Mesenchymal progenitor cells(MPCs),which play a central role in tissue repair,are pa...Aging is characterized by progressive functional decline driven by stem cell exhaustion,chronic inflammation,and cellular senescence.Mesenchymal progenitor cells(MPCs),which play a central role in tissue repair,are particularly vulnerable to age-associated dysfunction.Lei et al.(Cell 188:1-22,2025)address this limitation by engineering human embryonic stem cell-derived MPCs with enhanced FOXO3 activity(termed SRCs).Intravenous administration of FOXO3-SRCs to aged cynomolgus macaques significantly slowed aging across multiple organs compared to wild-type MPCs.SRC treatment improved cognitive performance,preserved brain structure,protected bone integrity,and rejuvenated immune function.Transcriptomic and DNA methylation aging clocks revealed substantial reductions in biological age,with the most pronounced rejuvenation observed in the reproductive system,skin,lung,muscle,and hippocampus.These effects were partly attributed to SRC-derived exosomes enriched in gero-protective proteins and metabolites.Importantly,SRCs exhibited robust safety,showing no tumorigenicity or immunogenicity.This work positions FOXO3-enhanced MPCs and their exosomes as promising candidates for systemic anti-aging interventions,shifting the therapeutic paradigm from treating individual diseases to targeting the aging process itself.展开更多
基金Supported by the National Natural Science Foundation of China (11171244)
文摘By means of mathematical modeling methods, we analyzed the relationship between the resistance to fluoroquinolones and GyrA mutation of Salmonella from animal isolates. We found that considering the influence of the resistance to ciprofloxacin hydrochloride, enrofloxacin, ofloxacin, pefloacin mesylate and norfloxacin nicotinate of the five types of fluoroquinolones to GyrA mutation of animal Salmonella, the resistance of pefloacin mesylate had the most significant effect, while the resistance of ciprofloxacin hydrochloride and enrofloxacin were the least significant factors. Nearly half of the Salmonella supports such a rule that the MIC of norfloxacin nicotinate reaching 64 or 128 might lead to the mutation Ser83→Phe, MIC exceeding 512 might lead to the mutation Ser83→Gly; 60% of the sample supported that the MIC of enrofloxacin reaching 32 or 64 might lead to the mutation Asp87 →Asn. 80% of them agreed to the fact that the MIC of neither ciprofloxacin hydrochloride under 64 nor pefloacin mesylate below 512 might result in the gene mutation in 119 site. All Salmonella isolates supported the conclusion that the mutation Alal19→Val took place, if and only if the MIC of norfloxacin nicotinate exceeded 512.
基金This study was financially supported by Conquer Chiari.
文摘Precise assessment of spinal cord cystic lesions is crucial to formulate effective therapeutic strategies,yet histological assessment of the lesion remains the primary method despite numerous studies showing inconsistent results regarding estimation of lesion size via histology.On the other hand,despite numerous advances in micro-computed tomography(micro-CT)imaging and analysis that have allowed precise measurements of lesion size,there is not enough published data on its application to estimate intraspinal lesion size in laboratory animal models.This work attempts to show that micro-CT can be valuable for spinal cord injury research by demonstrating accurate estimation of syrinx size and compares between micro-CT and traditional histological analysis.We used a post-traumatic syringomyelia rat model to compare micro-CT analysis to conventional histological analysis.The study showed that micro-CT can detect lesions within the spinal cord very similar to histology.Importantly,micro-CT appears to provide more accurate estimates of the lesions with more measures(e.g.,surface area),can detect compounds within the cord,and can be done with the tissue of interest(spinal cord)intact.In summary,the experimental work presented here provides one of the first investigations of the use of micro-CT for estimating the size of intraparenchymal cysts and detecting materials within the spinal cord.All animal procedures were approved by the University of Akron Institutional Animal Care and Use Committee(IACUC)(protocol#LRE 16-05-09 approved on May 14,2016).
文摘Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryotic translation initiation factor (eIF)4E, its isoforms, eIF(iso)4E, and the cap-binding protein (CBP) in plants, have been implicated in viral infections aside from their importance in protein synthesis. Full-length cDNA encoding these putative eIF targets from susceptible/resistant and unknown hexaploid sweetpotato (Ipomoea batatas L. Lam) were amplified based on primers designed from the diploid wild-type relative Ipomoea trifida consensus sequences, and designated IbeIF4E, IbeIF(iso)4E and IbCBP. Comparative analyses following direct-sequencing of PCR-amplified cDNAs versus the cloned cDNA sequences identified multiple homeoalleles: one to four IbeIF4E, two to three IbeIF(iso)4E, and two IbCBP within all cultivars tested. Open reading frames were in the length of 696 bp IbeIF4E, 606 bp IbeIF(iso)4E, and 675 bp IbCBP. The encoded single polypeptide lengths were 232, 202, and 225 amino acids for IbeIF4E, IbeIF(iso)4E, and IbCBP, with a calculated protein molecular mass of 26 kDa, 22.8 kDa, and 25.8 kDa, while their theoretical isoelectric points were 5.1, 5.57, and 6.6, respectively. Although the homeoalleles had similar sequence lengths, single nucleotide polymorphisms and multi-allelic variations were detected within the coding sequences. The multi-sequence alignment performed revealed a 66.9% - 96.7% sequence similarity between the predicted amino acid sequences obtained from the homeoalleles and closely related species. Furthermore, phylogenetic analysis revealed ancestral relationships between the eIF4E homeoalleles and other species. The outcome herein on the eIF4E superfamily and its correlation in sequence variations suggest opportunities to decipher the role of eIF4E in hexaploid sweetpotato feathery mottle virus infection.
文摘Several quinolino-benzoxaborole derivatives have been prepared to start from aminobenzoxaboroles. These derivatives have been evaluated for their anti-cancer activity on human and murine cancer cell lines and based on their relative non-toxicity, these compounds were further evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis. The synthesized compounds were also evaluated for antifungal activity in C. albicans and C. neoformans.
基金supported by CIRM fellowshipssupported by grants from the G.Harold and Leila Y.Mathers Charitable Foundation,The California Institute of Regenerative Medicine,Ellison Medical Foundation,and The Leona M.and Harry B.Helmsley Charitable Trust grant#2012-PG-MED002supported by the KAUST Office of Sponsored Research(OSR)under Award No.BAS/1/1080-01(ML),URF/1/4716-01(ML)and KAUST Center of Excellence for Smart Health(KCSH)award number 5932.
文摘Human pluripotent stem cells(hPSCs)can in theory give rise to any hematopoietic lineages,thereby offering opportunities for disease modeling,drug screening and cell therapies.However,gaps in our knowledge of the signaling requirements for the specification of human hematopoietic stem/progenitor cells(HSPCs),which lie at the apex of all hematopoietic lineages,greatly limit the potential of hPSC in hematological research and application.Transcriptomic analysis reveals aberrant regulation of WNT signaling during maturation of hPSC-derived hematopoietic progenitor cells(hPSC-HPCs),which results in higher mitochondria activity,misregulation of HOX genes,loss of self-renewal and precocious differentiation.These defects are partly due to the activation of the WNT target gene CDX2.Late-stage WNT inhibition improves the yield,self-renewal,multilineage differentiation,and transcriptional and metabolic profiles of hPSC-HPCs.Genome-wide mapping of transcription factor(TF)accessible chromatin reveals a significant overrepresentation of myeloid TF binding motifs in hPSC-HPCs,which could underlie their myeloid-biased lineage potential.Together our findings uncover a previously unappreciated dynamic requirement of the WNT signaling pathway during the specification of human HSPCs.Modulating the WNT pathway with small molecules normalizes the molecular differences between hPSC-HPCs and endogenous hematopoietic stem cells(HSCs),thereby representing a promising approach to improve the differentiation and function of hPSC-HPCs.
基金Supported by a grant from the US Department of Energy and by funds from the Eberly College of Science, the Department of Biology, and the Huck Institutes of the Life Sciences at the Pennsylvania State University. Publication of this paper is supported by the National Natural Science Foundation of China （30624808） and Science Publication Foundation of the Chinese Academy of Sciences.This manuscript was largely based on a lecture given at Changsha in May 2006 and is not meant to be a comprehensive review of the field of anther and pollen development. We apologize for not including some of the recent works because of time constraints. We thank B. Bliss, B. Feng, Y. Hu, A. Surce and A. Wijeratne for helpful comments on the manuscript.
文摘Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characterization of genes that are critical for normal cell division and differentiation in Arabidopsis early anther development. We review here several recent studies on these genes, including the demonstration that the putative receptor protein kinases BAM1 and BAM2 together play essential roles in the control of early cell division and differentiation. In addition, we discuss the hypothesis that BAM1/2 may form a positive-negative feedback regulatory loop with a previously identified key regulator, SPOROCYTELESS （also called NOZZLE）, to control the balance between sporogenous and somatic cell types in the anther. Furthermore, we summarize the isolation and functional analysis of the DYSFUNCTIONAL TAPETUM1 （DYT1） gene in promoting proper tapetal cell differentiation. Our finding that DYT1 encodes a putative transcription factor of the bHLH family, as well as relevant expression analyses, strongly supports a model that DYT1 serves as a critical link between upstream factors and downstream target genes that are critical for normal tapetum development and function. These studies, together with other recently published works, indicate that cell-cell communication and transcriptional control are key processes essential for cell fate specification in anther development.
文摘Microalgae are widely used in the pharmaceutical and energy industries,therefore the conditions for their cultivation and extraction methods play an important role in the profiling and acquisition of lipids.The efficiency of lipid extraction from microalgae has attracted great interest from industry because of the wide variety of lipids and amounts that can be obtained.Acutodesmus obliquus(Scenedesmus obliquus UTEX 393)was used in this study.It was cultivated in Bold 3N medium modified with 75%nitrogen at 25℃,pH 6.8,125 r/min and a photoperiod of 18/6 h and illuminated with white light provided by a Light-Emitting Diode Surface Mount Device extensions(LED SMD)with an intensity of 1200μE/(m^(2)·s).The cells were stained with the Red Nile(RN)technique to indicate lipid production.Four extraction methods were compared,classical,microwave(MW),Soxhlet,and ultrasound(US),using the same solvent proportions(hexane:chloroform:methanol=1:2:3).All samples were analyzed with Fourier Transform Infrared Spectroscopy(FTIR)and Gas Chromatography coupled to Mass Spectrometry(GC-MS).The results showed:1)lipid production detected by RN was consistent with microalgal growth;2)the MW technique was the best extraction method,according to the statistical analysis through Randomized Complete Block(RCB)design and performance of 4.6%;and 3)the presence of saturated and unsaturated acids was indicated by FTIR spectra.GC-MS was able to identify palmitic and linoleic acids as the likely major constituents of the sample.
基金supported by King Abdullah University of Science and Technology(KAUST)Office of Sponsored Research(OSR),under award number BAS/1/1080-01by KAUST Center of Excellence for Smart Health(KCSH),under award number 5932(ML)supported by the KAUST Center of Excellence for Smart Health(KCSH).
文摘Aging is characterized by progressive functional decline driven by stem cell exhaustion,chronic inflammation,and cellular senescence.Mesenchymal progenitor cells(MPCs),which play a central role in tissue repair,are particularly vulnerable to age-associated dysfunction.Lei et al.(Cell 188:1-22,2025)address this limitation by engineering human embryonic stem cell-derived MPCs with enhanced FOXO3 activity(termed SRCs).Intravenous administration of FOXO3-SRCs to aged cynomolgus macaques significantly slowed aging across multiple organs compared to wild-type MPCs.SRC treatment improved cognitive performance,preserved brain structure,protected bone integrity,and rejuvenated immune function.Transcriptomic and DNA methylation aging clocks revealed substantial reductions in biological age,with the most pronounced rejuvenation observed in the reproductive system,skin,lung,muscle,and hippocampus.These effects were partly attributed to SRC-derived exosomes enriched in gero-protective proteins and metabolites.Importantly,SRCs exhibited robust safety,showing no tumorigenicity or immunogenicity.This work positions FOXO3-enhanced MPCs and their exosomes as promising candidates for systemic anti-aging interventions,shifting the therapeutic paradigm from treating individual diseases to targeting the aging process itself.
