Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes af...Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.展开更多
Crassostrea nippona is a valuable species for aquaculture with considerable potential for commercial oyster farming.However,it is vulnerable to changes in salinity levels in coastal environments.In this study,we inves...Crassostrea nippona is a valuable species for aquaculture with considerable potential for commercial oyster farming.However,it is vulnerable to changes in salinity levels in coastal environments.In this study,we investigated the impacts of low salinity stress on the physiological responses of C.nippona.The hemolymph osmolality could not reach equilibrium with the surrounding environmental osmolality that was below salinity 15 within 1 week.Cell expansion,cellular valuocation,decrease of gill cilia,increased apoptotic cells under salinity 10 were observed through microscopic techniques.The activities of immunity-related enzymes,including alkaline phosphatase(AKP),acid phosphatase(ACP),superoxide dismutase(SOD),and catalase(CAT),were significantly increased at salinity 10 compared with the control group.These findings highlight the vulnerability of C.nippona to low salinity stress and provide insights into the physiological changes in response to fluctuating salinity levels.Understanding these physiological responses is crucial for effective aquaculture management and developing strategies to mitigate the negative impacts of low salinity stress on C.nippona populations in coastal areas.展开更多
Carotenoids play crucial physiological roles in animals.A comprehensive investigation into the mechanism of carotenoid metabolism in oysters will establish a theoretical foundation for further development of its carot...Carotenoids play crucial physiological roles in animals.A comprehensive investigation into the mechanism of carotenoid metabolism in oysters will establish a theoretical foundation for further development of its carotenoid-rich traits.However,the information on the function of miRNA in β-carotene metabolism in oysters is limited.To elucidate the mechanisms underlying miRNA regulation of carotenoid metabolism in oysters,we compared the expressions of miRNA in digestive gland tissues of Pacific oyster(Crassostrea gigas)fed with aβ-carotene supplemented diet and a normal diet,respectively.A total of 690 candidate miRNAs in the Pacific oyster digestive gland tissues were identified,including 590 known miRNAs and 111 unknown miRNAs.Three differentially expressed miRNAs were obtained in the carotenoid-fed and normal groups,associated to 137 differentially expressed target genes.Moreover,the GO enrichment analysis revealed that the differentially expressed target genes were mainly involved in transmembrane transport activity.KEGG enrichment showed that the differentially expressed target genes were involved in ABC transport.Analysis of the mRNA-miRNA network revealed that novel0025 played a central role in carotenoid metabolism,and it was negatively correlated with the expression of 46 mRNAs.In addition,down-regulated expression of novel0025 upregulated the expression of the lipoprotein gene LOC105342186,suggesting a potential regulatory role in carotenoid metabolism.Our results provide useful information for elucidating the miRNA regulation mechanism during carotenoids metabolism in the Pacific oyster.展开更多
Heterosis has been exploited to enhance the yield and adaptability in various shellfish species;however,the molecular basis of it remains unclear.The Pacific oyster Crassostrea gigas is one of the most economically im...Heterosis has been exploited to enhance the yield and adaptability in various shellfish species;however,the molecular basis of it remains unclear.The Pacific oyster Crassostrea gigas is one of the most economically important aquaculture species,and its productive traits can be improved by hybridization.Here,an intraspecific cross between orange shell(O,10th generation)and‘Haida No.1’(H,13th generation)of C.gigas was performed to assess the heterosis of survival trait.Survival rates of hybrid family(OH)and inbred families(HH and OO)were compared at larval stage,and eyed-pediveliger larvae of three families were subjected to transcriptome analysis.The analysis results of best-parent heterosis and mid-parent heterosis showed that the hybrid family exhi-bited a high heterosis in survival relative to the parental families.The OH-M(OH vs.OO)and OH-P(OH vs.HH)had 425 and 512 dif-ferentially expressed genes(DEGs),respectively.Functional enrichment analysis of these DEGs revealed that the significantly enrich-ed genes function in virion binding,C-type lectin receptor signaling pathway,cellular defense response and other immune-related pro-cesses,which involves perlucin-like protein,CD209 antigen-like protein,ZNFX1,caspase-3 and acan genes.These differentially ex-pressed genes in OH-M and OH-P,together with the immune-related processes mentioned above may play an important role in the larval survival of C.gigas.In addition,three genes(CYP450,fucolectin and perlucin-like)are associated with the orange shell and low survival of maternal oyster OO.These findings provide support for the application of hybrid with superior survival and will facilitate the understanding of heterosis formation in the Pacific oyster.展开更多
Pacific oyster(Crassostrea gigas)is one of the most important mollusks cultured all around the world.Selective breeding programs of Pacific oysters in China is initiated since 2006 and developed the genetically improv...Pacific oyster(Crassostrea gigas)is one of the most important mollusks cultured all around the world.Selective breeding programs of Pacific oysters in China is initiated since 2006 and developed the genetically improved strain with fast-growing trait.However,little is known about the metabolic signatures of the fast-growing trait.In the present study,the non-targeted metabolomics was performed to analyze the metabolic signatures of adductor muscle tissue in one-year old Pacific oysters from fast-growing strain and the wild population.A total of 7767 and 10174 valid peaks were extracted and quantified in ESI^(+)and ESI^(−)modes,resulting in 399 and 381 annotated metabolites,respectively.PCA and OPLS-DA revealed that considerable separation among samples from fastgrowing strain and wild population,suggesting the differences in metabolic signatures.Meanwhile,81 significantly different metabolites(SDMs)were identified in the comparisons between fast-growing strain and wild population,based on the strict thresholds.It was found that there were highly correlation and conserved coordination among these SDMs.KEGG enrichment analysis indicated that the SDMs were tightly related to pantothenate and CoA biosynthesis,steroid hormone biosynthesis,riboflavin metabolism,and arginine and proline metabolism.Of them,the CoA biosynthesis and metabolism,affected by pantetheine and pantothenic acid,might be important for the growth of Pacific oysters under artificial selective breeding.The study provides the comprehensive views of metabolic signatures in response to artificially selective breeding,and is helpful to better understand the molecular mechanism of fastgrowing traits in Pacific oysters.展开更多
Chronic obstructive pulmonary disease(COPD)is one of the most common and important diseases leading to the death of elderly patients in the world at present.It is characterized by continuous airflow restriction and ir...Chronic obstructive pulmonary disease(COPD)is one of the most common and important diseases leading to the death of elderly patients in the world at present.It is characterized by continuous airflow restriction and irreversible chronic airway obstruction,which can easily lead to a variety of complications and accompanying symptoms,greatly affecting the quality of life of individuals and increasing the economic burden of families and society.Pulmonary embolism(PE)is one of the complications of COPD,which can lead to pulmonary blood circulation and respiratory failure,with a high risk of death.However,because its clinical symptoms overlap with the symptoms of acute exacerbation of COPD and lack of specific clinical manifestations and laboratory tests,it is easy to be misdiagnosed and ignored,thus delaying the treatment of patients and affecting the prognosis.This article will elaborate on the clinical diagnosis and treatment of chronic obstructive pulmonary disease combined with pulmonary embolism,providing certain value for early identification of COPD combined with PE patients and the severity of the condition.展开更多
Abstract Four successive mass selection lines of the Pacific oyster, Crassostrea gigas, selected for faster growth in breeding pro- grams in China were examined at ten polymorphic microsatellite loci to assess the lev...Abstract Four successive mass selection lines of the Pacific oyster, Crassostrea gigas, selected for faster growth in breeding pro- grams in China were examined at ten polymorphic microsatellite loci to assess the level of allelic diversity and estimate the effective population size. These data were compared with those of their base population. The results showed that the genetic variation of the four generations were maintained at high levels with an average allelic richness of 18.8-20.6, and a mean expected heterozygosity of 0.902-0.921. They were not reduced compared with those of their base population. Estimated effective population sizes based on temporal variances in microsatellite frequencies were smaller to that of sex ratio-corrected broodstock count estimates. Using a rela- tively large number ofbroodstock and keeping an equal sex ratio in the broodstock each generation may have contributed to retaining the original genetic diversity and maintaining relatively large effective population size. The results obtained in this study showed that the genetic variation was not affected greatly by mass selection progress and high genetic variation still existed in the mass selection lines, suggesting that there is still potential for increasing the gains in future generations of C. gigas. The present study provided im- portant information for future genetic improvement by selective breeding, and for the design of suitable management guidelines for genetic breeding of C. gigas.展开更多
基金supported by NIH grants RF1 AG069466(to JL and LDM),R01 NS099628(to JL),and AG069466(to JL and LDM)the American Heart Association award 20POST35180172(to FB)。
文摘Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.
基金supported by the National Key R&D Program of China(No.2022YFD2400305)the Earmarked Fund for Agriculture Seed Improvement Project of Shandong Province(Nos.2021ZLGX03,2022LZGCQY010 and 2021LZGC027)the China Agriculture Research System Project(No.CARS-49)。
文摘Crassostrea nippona is a valuable species for aquaculture with considerable potential for commercial oyster farming.However,it is vulnerable to changes in salinity levels in coastal environments.In this study,we investigated the impacts of low salinity stress on the physiological responses of C.nippona.The hemolymph osmolality could not reach equilibrium with the surrounding environmental osmolality that was below salinity 15 within 1 week.Cell expansion,cellular valuocation,decrease of gill cilia,increased apoptotic cells under salinity 10 were observed through microscopic techniques.The activities of immunity-related enzymes,including alkaline phosphatase(AKP),acid phosphatase(ACP),superoxide dismutase(SOD),and catalase(CAT),were significantly increased at salinity 10 compared with the control group.These findings highlight the vulnerability of C.nippona to low salinity stress and provide insights into the physiological changes in response to fluctuating salinity levels.Understanding these physiological responses is crucial for effective aquaculture management and developing strategies to mitigate the negative impacts of low salinity stress on C.nippona populations in coastal areas.
基金supported by grants from the Shandong Science and Technology Small and Medium Enterprises Innovation Ability Improvement Project (No.2021TSGC 1240)the Key R&D Program of Shandong Province,China (No.2022TZXD002)the China Agriculture Research System Project (No.CARS-49)。
文摘Carotenoids play crucial physiological roles in animals.A comprehensive investigation into the mechanism of carotenoid metabolism in oysters will establish a theoretical foundation for further development of its carotenoid-rich traits.However,the information on the function of miRNA in β-carotene metabolism in oysters is limited.To elucidate the mechanisms underlying miRNA regulation of carotenoid metabolism in oysters,we compared the expressions of miRNA in digestive gland tissues of Pacific oyster(Crassostrea gigas)fed with aβ-carotene supplemented diet and a normal diet,respectively.A total of 690 candidate miRNAs in the Pacific oyster digestive gland tissues were identified,including 590 known miRNAs and 111 unknown miRNAs.Three differentially expressed miRNAs were obtained in the carotenoid-fed and normal groups,associated to 137 differentially expressed target genes.Moreover,the GO enrichment analysis revealed that the differentially expressed target genes were mainly involved in transmembrane transport activity.KEGG enrichment showed that the differentially expressed target genes were involved in ABC transport.Analysis of the mRNA-miRNA network revealed that novel0025 played a central role in carotenoid metabolism,and it was negatively correlated with the expression of 46 mRNAs.In addition,down-regulated expression of novel0025 upregulated the expression of the lipoprotein gene LOC105342186,suggesting a potential regulatory role in carotenoid metabolism.Our results provide useful information for elucidating the miRNA regulation mechanism during carotenoids metabolism in the Pacific oyster.
基金supported by the grants from the China Agriculture Research System Project(No.CARS-49)the Earmarked Fund for Agriculture Seed Improvement Project of Shandong Province(No.2020LZGC016).
文摘Heterosis has been exploited to enhance the yield and adaptability in various shellfish species;however,the molecular basis of it remains unclear.The Pacific oyster Crassostrea gigas is one of the most economically important aquaculture species,and its productive traits can be improved by hybridization.Here,an intraspecific cross between orange shell(O,10th generation)and‘Haida No.1’(H,13th generation)of C.gigas was performed to assess the heterosis of survival trait.Survival rates of hybrid family(OH)and inbred families(HH and OO)were compared at larval stage,and eyed-pediveliger larvae of three families were subjected to transcriptome analysis.The analysis results of best-parent heterosis and mid-parent heterosis showed that the hybrid family exhi-bited a high heterosis in survival relative to the parental families.The OH-M(OH vs.OO)and OH-P(OH vs.HH)had 425 and 512 dif-ferentially expressed genes(DEGs),respectively.Functional enrichment analysis of these DEGs revealed that the significantly enrich-ed genes function in virion binding,C-type lectin receptor signaling pathway,cellular defense response and other immune-related pro-cesses,which involves perlucin-like protein,CD209 antigen-like protein,ZNFX1,caspase-3 and acan genes.These differentially ex-pressed genes in OH-M and OH-P,together with the immune-related processes mentioned above may play an important role in the larval survival of C.gigas.In addition,three genes(CYP450,fucolectin and perlucin-like)are associated with the orange shell and low survival of maternal oyster OO.These findings provide support for the application of hybrid with superior survival and will facilitate the understanding of heterosis formation in the Pacific oyster.
基金supported by grants from the Earmarked Fund for Agriculture Seed Improvement Project of Shandong Province(Nos.2021ZLGX03 and 2022LZGCQY010)the China Agriculture Research System Project(No.CARS-49).
文摘Pacific oyster(Crassostrea gigas)is one of the most important mollusks cultured all around the world.Selective breeding programs of Pacific oysters in China is initiated since 2006 and developed the genetically improved strain with fast-growing trait.However,little is known about the metabolic signatures of the fast-growing trait.In the present study,the non-targeted metabolomics was performed to analyze the metabolic signatures of adductor muscle tissue in one-year old Pacific oysters from fast-growing strain and the wild population.A total of 7767 and 10174 valid peaks were extracted and quantified in ESI^(+)and ESI^(−)modes,resulting in 399 and 381 annotated metabolites,respectively.PCA and OPLS-DA revealed that considerable separation among samples from fastgrowing strain and wild population,suggesting the differences in metabolic signatures.Meanwhile,81 significantly different metabolites(SDMs)were identified in the comparisons between fast-growing strain and wild population,based on the strict thresholds.It was found that there were highly correlation and conserved coordination among these SDMs.KEGG enrichment analysis indicated that the SDMs were tightly related to pantothenate and CoA biosynthesis,steroid hormone biosynthesis,riboflavin metabolism,and arginine and proline metabolism.Of them,the CoA biosynthesis and metabolism,affected by pantetheine and pantothenic acid,might be important for the growth of Pacific oysters under artificial selective breeding.The study provides the comprehensive views of metabolic signatures in response to artificially selective breeding,and is helpful to better understand the molecular mechanism of fastgrowing traits in Pacific oysters.
基金National Key Research and Development Program(No.2022YFC2305004)Key Research and Development Project of Hainan Province(No.ZDYF2020223)+2 种基金Key Science and Technology Project of Hainan Province(No.ZDKJ2021036)International Science and Technology Cooperation Project of Hainan Provincial Key Research and Development Program(No.GHYF2022011)National Natural Science Foundation of China(No.82260001,82160012)。
文摘Chronic obstructive pulmonary disease(COPD)is one of the most common and important diseases leading to the death of elderly patients in the world at present.It is characterized by continuous airflow restriction and irreversible chronic airway obstruction,which can easily lead to a variety of complications and accompanying symptoms,greatly affecting the quality of life of individuals and increasing the economic burden of families and society.Pulmonary embolism(PE)is one of the complications of COPD,which can lead to pulmonary blood circulation and respiratory failure,with a high risk of death.However,because its clinical symptoms overlap with the symptoms of acute exacerbation of COPD and lack of specific clinical manifestations and laboratory tests,it is easy to be misdiagnosed and ignored,thus delaying the treatment of patients and affecting the prognosis.This article will elaborate on the clinical diagnosis and treatment of chronic obstructive pulmonary disease combined with pulmonary embolism,providing certain value for early identification of COPD combined with PE patients and the severity of the condition.
基金supported by grants from the National High Technology Research and Development Program (2012AA10A405-6)National Natural Science Foundation of China (31372524)Special Fund for Independent Innovation of Shandong Province (2013CX80202)
文摘Abstract Four successive mass selection lines of the Pacific oyster, Crassostrea gigas, selected for faster growth in breeding pro- grams in China were examined at ten polymorphic microsatellite loci to assess the level of allelic diversity and estimate the effective population size. These data were compared with those of their base population. The results showed that the genetic variation of the four generations were maintained at high levels with an average allelic richness of 18.8-20.6, and a mean expected heterozygosity of 0.902-0.921. They were not reduced compared with those of their base population. Estimated effective population sizes based on temporal variances in microsatellite frequencies were smaller to that of sex ratio-corrected broodstock count estimates. Using a rela- tively large number ofbroodstock and keeping an equal sex ratio in the broodstock each generation may have contributed to retaining the original genetic diversity and maintaining relatively large effective population size. The results obtained in this study showed that the genetic variation was not affected greatly by mass selection progress and high genetic variation still existed in the mass selection lines, suggesting that there is still potential for increasing the gains in future generations of C. gigas. The present study provided im- portant information for future genetic improvement by selective breeding, and for the design of suitable management guidelines for genetic breeding of C. gigas.
