This article examines an early 2nd century BC decree of an association worshipping Zeus Hyetios,“the provider of rain,”in the Koan deme of Antimacheia.Focusing on the prosopographical information of the five individ...This article examines an early 2nd century BC decree of an association worshipping Zeus Hyetios,“the provider of rain,”in the Koan deme of Antimacheia.Focusing on the prosopographical information of the five individuals mentioned in the decree,this article contextualizes the association’s activities within the broader framework of Hellenistic Kos,highlighting issues such as landownership,migration,and social structures,whilst exploring the association’s agricultural focus,its integration with local deme structures,and its strategies for managing the challenges of absentee landownership.This study also argues that the unusual name of the association reflects the frequent absence of its members from the central cult place,who therefore needed to travel a considerable distance in order to attend the cult’s rituals in Antimacheia.This case underscores the interplay between religious,social,and economic dynamics in rural communities.展开更多
Background Konjac oligosaccharide(KOS),which is produced through the degradation of konjac glucomannan via enzymatic,chemical,or physical treatments,has been found to have laxative effects.The current study aimed to e...Background Konjac oligosaccharide(KOS),which is produced through the degradation of konjac glucomannan via enzymatic,chemical,or physical treatments,has been found to have laxative effects.The current study aimed to elucidate the mechanisms underlying the laxative effect of KOS.Methods KOS was administered by gavage to wild-type and 5-hydroxytryptamine 4 receptor(5-HT4R)-knockout C57BL/6 mice subjected to loperamide-induced constipation for four weeks.Following treatment,feces,blood,small intestine,colonic tissue,and intestinal contents were collected.Constipation-related parameters,gastrointestinal hormones,and Ca2+concentrations were evaluated.Histopathological changes were examined via hematoxylin and eosin staining.Immunofluorescence staining,Western blotting,and immunohistochemical staining were performed to detect the 5-HT4R/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway.Isolated smooth muscle cells(SMCs)were treated with KOS and GR113808(a 5-HT4R antagonist),morphologically observed under an inverted microscope,and identified byα-SMA immunofluorescence staining.Cell viability was assessed via CCK-8 assays.5-HT4R/cAMP/PKA/p-CREB pathway activity in SMCs was detected via Western blotting.Results KOS alleviated loperamide-induced constipation in mice.KOS activated the 5-HT4R/cAMP/PKA/p-CREB pathway in loperamide-induced constipated mice.The protective effect of KOS was significantly diminished in 5-HT4R−/−mice.KOS promoted the proliferation of SMCs by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.Conclusion KOS improves loperamide-induced constipation by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.展开更多
Dear Editors,The term“developmental disconnection syndromes”(DDSs)was first coined by Geshwind and Levitt in 2007[1]to describe the weakening of already formed connections or an absence of certain connections to est...Dear Editors,The term“developmental disconnection syndromes”(DDSs)was first coined by Geshwind and Levitt in 2007[1]to describe the weakening of already formed connections or an absence of certain connections to establish correct organization de novo in early developmental stages.DDSs include a number of neuropsychiatric diseases,such as autistic spectrum disorder(ASD)[1,2],which is characterized by impaired social communication and repetitive and stereotyped behaviors.Nevertheless,the exact etiology underlying these“disconnections”and their abnormal developmental trajectory remains largely unclear.Even less known is whether developmental disconnections relevant to autism can be rescued by early intervention thereby preventing neuropsychiatric and repetitive symptoms in later stages.This study addresses these important questions.展开更多
Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult hom...Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.展开更多
Reactive oxygen species(ROS)are believed to be inevitable and toxic by-products produced during cellular respiration.However,several lines of evidence show that diverse extracellular signals can activate ROS productio...Reactive oxygen species(ROS)are believed to be inevitable and toxic by-products produced during cellular respiration.However,several lines of evidence show that diverse extracellular signals can activate ROS production and provide important function for various biological processes.展开更多
7α-Hydroxy-8β,9β-H- cis- bicyclo[4,3,0]non-4-ene-4-aldehyde, a nonane compound with novel skeleton, named tsaokoin, was isolated from the fruits of Amomum tsao-ko. Its structure was established on the basis of spec...7α-Hydroxy-8β,9β-H- cis- bicyclo[4,3,0]non-4-ene-4-aldehyde, a nonane compound with novel skeleton, named tsaokoin, was isolated from the fruits of Amomum tsao-ko. Its structure was established on the basis of spectral analysis.展开更多
The classic method for gene knockout (KO) is based on homologous recombination (HR) and embryonic stem cell technique (Gerlai,1996).Actually,the procedure of homologous replacement is complicated and time consuming,al...The classic method for gene knockout (KO) is based on homologous recombination (HR) and embryonic stem cell technique (Gerlai,1996).Actually,the procedure of homologous replacement is complicated and time consuming,although it has been popular during the past decades.Recent years,genome editing which can cause DNA sequence-specific mutations in the genomes of cellular展开更多
文摘This article examines an early 2nd century BC decree of an association worshipping Zeus Hyetios,“the provider of rain,”in the Koan deme of Antimacheia.Focusing on the prosopographical information of the five individuals mentioned in the decree,this article contextualizes the association’s activities within the broader framework of Hellenistic Kos,highlighting issues such as landownership,migration,and social structures,whilst exploring the association’s agricultural focus,its integration with local deme structures,and its strategies for managing the challenges of absentee landownership.This study also argues that the unusual name of the association reflects the frequent absence of its members from the central cult place,who therefore needed to travel a considerable distance in order to attend the cult’s rituals in Antimacheia.This case underscores the interplay between religious,social,and economic dynamics in rural communities.
文摘Background Konjac oligosaccharide(KOS),which is produced through the degradation of konjac glucomannan via enzymatic,chemical,or physical treatments,has been found to have laxative effects.The current study aimed to elucidate the mechanisms underlying the laxative effect of KOS.Methods KOS was administered by gavage to wild-type and 5-hydroxytryptamine 4 receptor(5-HT4R)-knockout C57BL/6 mice subjected to loperamide-induced constipation for four weeks.Following treatment,feces,blood,small intestine,colonic tissue,and intestinal contents were collected.Constipation-related parameters,gastrointestinal hormones,and Ca2+concentrations were evaluated.Histopathological changes were examined via hematoxylin and eosin staining.Immunofluorescence staining,Western blotting,and immunohistochemical staining were performed to detect the 5-HT4R/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway.Isolated smooth muscle cells(SMCs)were treated with KOS and GR113808(a 5-HT4R antagonist),morphologically observed under an inverted microscope,and identified byα-SMA immunofluorescence staining.Cell viability was assessed via CCK-8 assays.5-HT4R/cAMP/PKA/p-CREB pathway activity in SMCs was detected via Western blotting.Results KOS alleviated loperamide-induced constipation in mice.KOS activated the 5-HT4R/cAMP/PKA/p-CREB pathway in loperamide-induced constipated mice.The protective effect of KOS was significantly diminished in 5-HT4R−/−mice.KOS promoted the proliferation of SMCs by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.Conclusion KOS improves loperamide-induced constipation by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.
基金support JCS,QX,and BQ,as well as covering all experimental and material costs for this project,NIH/NIMH R01 MH094360-06(HWD)grant to support HX,MZ,Lei Gao,Lin Gou,HH and HWD.
文摘Dear Editors,The term“developmental disconnection syndromes”(DDSs)was first coined by Geshwind and Levitt in 2007[1]to describe the weakening of already formed connections or an absence of certain connections to establish correct organization de novo in early developmental stages.DDSs include a number of neuropsychiatric diseases,such as autistic spectrum disorder(ASD)[1,2],which is characterized by impaired social communication and repetitive and stereotyped behaviors.Nevertheless,the exact etiology underlying these“disconnections”and their abnormal developmental trajectory remains largely unclear.Even less known is whether developmental disconnections relevant to autism can be rescued by early intervention thereby preventing neuropsychiatric and repetitive symptoms in later stages.This study addresses these important questions.
文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.
基金supported by grants from the Korean Ministry of Trade,Industry and Energy(10063396)the National Research Foundation(NRF)of Korea(2018M3A9B8021980)
文摘Reactive oxygen species(ROS)are believed to be inevitable and toxic by-products produced during cellular respiration.However,several lines of evidence show that diverse extracellular signals can activate ROS production and provide important function for various biological processes.
文摘7α-Hydroxy-8β,9β-H- cis- bicyclo[4,3,0]non-4-ene-4-aldehyde, a nonane compound with novel skeleton, named tsaokoin, was isolated from the fruits of Amomum tsao-ko. Its structure was established on the basis of spectral analysis.
基金supported by the National Key Research and Development Plan of China(2017YFD0501602)the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five Plan(IDHT20170516)
文摘The classic method for gene knockout (KO) is based on homologous recombination (HR) and embryonic stem cell technique (Gerlai,1996).Actually,the procedure of homologous replacement is complicated and time consuming,although it has been popular during the past decades.Recent years,genome editing which can cause DNA sequence-specific mutations in the genomes of cellular
