A MADS box gene （GhMADS3） was cloned from cotton （Gossypium hirsutum L.） based on EST sequences. The predicted protein sequence of GhMADS3 showed 85%, 73%, and 62% identity with Theobroma cacao TcAG, Antirrhinum m...A MADS box gene （GhMADS3） was cloned from cotton （Gossypium hirsutum L.） based on EST sequences. The predicted protein sequence of GhMADS3 showed 85%, 73%, and 62% identity with Theobroma cacao TcAG, Antirrhinum majus FAR, and Arabidopsis thaliana AG, respectively, and was grouped with AG homologues when the full length sequences excluding N-extensions were compared. GhMADS3 expressed in the wild type cotton flower primarily in stamens and carpels, which was comparable to AG in Arabidopsis. However, it was not expressed in floral buds of a homeotic cotton variant chvl. Ectopic expression of GhMADS3 in tobacco （Nicotiana tabacum L.） resulted in flowers with sepal-to-carpel and petal-to-stamen transformation. The carpelloid first whorl organs, with stigmatic tissue on their upper edges, had a white appearance when compared with the dark green color of the wild type sepals. At times, long filaments were observed at the fusion site of the first carpelloid oranges. The second whorl organs in staminoid were usually smaller than the wild type and the color was changed from pink to white. These results suggest that GhMADS3 has a homeotic role in flower development.展开更多
Sequences from the mitochondrial cytochrome b gene （Cyt b） were determined for 25 species from the superfamily Acridoidae and the homologous sequences of 19 species of grasshoppers were downloaded from the GenBank d...Sequences from the mitochondrial cytochrome b gene （Cyt b） were determined for 25 species from the superfamily Acridoidae and the homologous sequences of 19 species of grasshoppers were downloaded from the GenBank data library. The purpose was to develop a molecular phylogeny of the Acrypteridae, and to interpret the phylogenetic position of the family within the superfamily Acridoidea. Phylogeny was reconstructed by Maximum-parsimony （MP） and Bayesian criteria using Yunnanites coriacea and Tagasta marginella as outgroups. The alignment length of the fragments was 384 bp after excluding ambiguous sites, including 167 parsimony informative sites. In the fragments, the percentages of A ＋ T and G ＋ C were 70.7% and 29.3%, respectively. The monophyly of Arcypteridae is not supported by phylogenetic trees. Within the Arcypteridae, neither Arcypterinae nor Ceracrinae is supported as a monophyletic group. The current genus Chorthippus is not a monophyletic group, and should be a polyphyletic group. The present results are significantly different from the classification scheme of Arcypteridae, which is based on morphology.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles...BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles in various cancers by influencing cell proliferation,invasion,and metastasis.AIM To analyze PEA3 subfamily gene expression levels in CCA and their correlation with clinical parameters to determine their prognostic value for CCA.METHODS The expression levels of PEA3 subfamily genes in pan-cancer and CCA data in the cancer genome atlas and genotype-tissue expression project databases were analyzed with R language software.Survival curve and receiver operating characteristic analyses were performed using the SurvMiner,Survival,and Procr language packages.The gene expression profiling interactive analysis 2.0 database was used to analyze the expression levels of PEA3 subfamily genes in different subtypes and stages of CCA.Web Gestalt was used to perform the gene ontology/Kyoto encyclopedia of genes and genomes(GO/KEGG)analysis,and STRING database analysis was used to determine the genes and proteins related to PEA3 subfamily genes.RESULTS ETV1,ETV4,and ETV5 expression levels were significantly increased in CCA.There were significant differences in ETV1,ETV4,and ETV5 expression levels among the different subtypes of CCA,and predictive analysis revealed that only high ETV1 and ETV4 expression levels were significantly associated with shorter overall survival in patients with CCA.GO/KEGG analysis revealed that PEA3 subfamily genes were closely related to transcriptional misregulation in cancer.In vitro and in vivo experiments revealed that PEA3 silencing inhibited the invasion and metastasis of CCA cells.CONCLUSION The expression level of ETV4 may be a predictive biomarker of survival in patients with CCA.展开更多
Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracell...Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracellular cholesterol in the foam ceils derived from rat VSMCs （rVSMCs） and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 （ABCA1）, adenosine triphosphate-binding cassette subfamily G member 1 （ABCG1） and peroxisome proliferator-activated receptor gamma （PPARy）. The rVSMCs were co-cultured with oxi- dized low density lipoprotein （LDL, 80 ~tg/mL） to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers （20, 40 and 60 pfu/cell） of recombinant adenovirus containing Mfn2 gene （Adv-Mfn2） were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group （P〈0.05）, and the ex- pression levels significantly increased when the titer of Adv-Mfn2 increased （P〈0.05）. At 24 or 48 h af- ter oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased （P〈0.05）, but it was sig- nificantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）, and it also significantly decreased when the titer of Adv-Mfn2 increased （P〈0.05）. The mRNA and pro- tein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. Though the mRNA and protein 展开更多
The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whe...The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.展开更多
BACKGROUND Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery.However,some patients may develop postope-rative complications,liver failure,and other life-t...BACKGROUND Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery.However,some patients may develop postope-rative complications,liver failure,and other life-threatening situations.Here,we report a patient with mutations in the uridine 5’-diphospho-glucuronosyltrans-ferase 1A1(UGT1A1)and bile salt export pump(adenosine triphosphate-binding cassette subfamily B member 11,ABCB11)genes who presented multiple intrahe-patic bile duct stones and cholestasis,and the jaundice of the patient increased after partial hepatectomy.CASE SUMMARY A 52-year-old male patient admitted to the hospital on October 23,2021,with a progressive exacerbation of jaundice,was found to have multiple intrahepatic bile duct stones with the diagnoses of obstructive jaundice and acute cholecystitis.Subsequently,the patient underwent left hepatectomy with biliary exploration,stone extraction,T-tube drainage,and cholecystectomy without developing any intraoperative complications.The patient had a dark urine color with worsening jaundice postoperatively and did not respond well to plasma exchange and other symptomatic and supportive treatments.Since the progressive increase in postoperative bilirubin could not be clinically explained with any potential reason,including,if not at all,viral infection,cholangitis,autoimmune liver disease,and other causes,the patient underwent whole-exon screening for any genetic diseases,which surprisingly identified UGT1A1 and ABCB11 gene mutations related to glucuronidation of indirect bilirubin as well as bile acid transport in hepatocytes,respectively.Thus,we hypothesized that postoperative refractory cholestasis might result from UGT1A1 and ABCB11 gene mutations and further recommended liver transplantation to the patient,who eventually declined it and died from liver failure six months later.CONCLUSION Surgery may aggravate cholestasis in patients with multiple intrahepatic bile duct stones and cholestasis associated with UGT1A1 and ABCB11 gene mutations展开更多
A total of 321 individuals from six cattle populations of four species in a bovine subfamily in China were studied using 12 pairs of microsatellite markers. The genetic diversities within and between populations were ...A total of 321 individuals from six cattle populations of four species in a bovine subfamily in China were studied using 12 pairs of microsatellite markers. The genetic diversities within and between populations were calculated. The phylogenetic trees were constructed by （δμ）^2 and DA distances, and the divergence times between populations were estimated by （δμ）^2. Altogether, 144 microsatellite alleles were detected including 24 private alleles and nine shared alleles. Chinese Holstein had the largest number of private alleles （10）, whereas Bohai black and Buffalo had the smallest number of private alleles （2）. Chinese Holstein showed the highest genetic variability. Its observed number of alleles （Na）, mean effective number of alleles （MNA）, and mean heterozygosity （He） were 7.7500, 4.9722, and 0.7719, respectively, whereas, the Buffalo and Yak showed low genetic variability. In the phylogenetic trees, Luxi and Holstein grouped first, followed by Bohai and Minnan. Yak branched next and buffalo emerged as the most divergent population from other cattle populations. Luxi and Bohai were estimated to have diverged 0.039-0.105 million years ago （MYA）, however, buffalo and Holstein diverged 0.501-1.337 MYA. The divergence time of Yak versus Minnan, Holstein and buffalo was 0.136-0.363, 0.273-0.729, and 0.326-0.600 MYA, respectively.展开更多
OBJECTIVE:To investigate the antagonistic effect of the extract of Baizhu(Rhizoma Atractylodis Macrocephalae)(RAM)on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica(NUX)and propose the mech...OBJECTIVE:To investigate the antagonistic effect of the extract of Baizhu(Rhizoma Atractylodis Macrocephalae)(RAM)on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica(NUX)and propose the mechanism of these effects.METHODS:The apparent permeability value(Papp)and absorption rate constant(Ka)were chosen as indices.The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine.To confirm the results,the brucine and strychnine concentrations in hepatic portal venous blood were determined.Western blotting was used to study P-glycoprotein(P-gp)expression in the Caco-2 cell line.RESULTS:Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor,but no significant increase was noted in the presence of a tight junction regulator.The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression.CONCLUSION:The primary absorption mechanism for brucine and strychnine is passive transport,which is affected by P-gp.展开更多
The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Au...The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.展开更多
Betulinic acid(BA),a penta-cyclic triterpenoid found as a ubiquitous secondary metabolite throughout the plant kingdom,has aroused tremendous interests due to its different pharmacological properties,which lead to lar...Betulinic acid(BA),a penta-cyclic triterpenoid found as a ubiquitous secondary metabolite throughout the plant kingdom,has aroused tremendous interests due to its different pharmacological properties,which lead to large market demand.However,the content of BA in plant is low for phytoextraction.Although chemical semi-synthesis or biotransformation of BA from betulin with high conversion efficiency is achieved,it still relies on phytoextraction from the bark of medicinal trees.To circumvent this issue,the biotechnological synthesis of BA in engineered yeasts has been developed.In this review,the pharmacological properties of BA are first summarized,including antitumor,anti-HIV,antiprotozoal,anti-inflammatory,apoptosis activator and anti-metabolic syndrome.Then,the traditional phytoextraction,semi-synthesis and biotechnological synthesis of BA are discussed.Particularly,current advances in its biotechnological synthesis and strategies to improve BA production are focused.Moreover,potential strategies for further promotion of BA yield,including the introduction of artificial isopentenol utilization pathway,semi-rational mutagenesis of lupeol synthase and cytochrome P450,and subcellular morphology and compartmentalization,are discussed.展开更多
Objective:Due to the characteristics of insidious onset and early metastasis of pancreatic cancer(PC),patients are often diag-nosed at an advanced stage and often delayed in completing surgical resection timely,result...Objective:Due to the characteristics of insidious onset and early metastasis of pancreatic cancer(PC),patients are often diag-nosed at an advanced stage and often delayed in completing surgical resection timely,resulting in poor prognosis.Therefore,this study aims to explore the expression of potassium voltage-gated channel subfamily H member 2(KCNH2)in PC and its relation-ship with clinicopathological parameters and the related mechanisms.Methods:GEPIA database and immunohistochemical staining were used to analyze the difference in KCNH2 expression be-tween PC and adjacent tissue in RNA and protein levels.Chi-squared test was used to evaluate the relationship between KCNH2 expression and clinicopathological features.The Cox regression model was used for multivariate analysis and univariate analysis.Histological diagnosis was performed according to World Health Organization(WHO)criteria to evaluate the relationship between KCNH2 expression and clinicopathological features.Results:KCNH2 expression was upregulated in PC compared with normal pancreatic tissue.In addition,the knockdown of KCNH2 inhibits PC cell proliferation,migration,invasion,and epithelial-mesenchymal transformation and promotes their apopto-sis.In addition,clinical data showed that the abnormal expression of KCNH2 in PC was related to the tumor stage.Patients with high expression of KCNH2 had a poor prognosis.Conclusions:KCNH2 is expected to be a novel targeted molecule in treating PC.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.30070485)Southwest University InitialResearch Foundation Grant to Doctor(No.D200404).
文摘A MADS box gene （GhMADS3） was cloned from cotton （Gossypium hirsutum L.） based on EST sequences. The predicted protein sequence of GhMADS3 showed 85%, 73%, and 62% identity with Theobroma cacao TcAG, Antirrhinum majus FAR, and Arabidopsis thaliana AG, respectively, and was grouped with AG homologues when the full length sequences excluding N-extensions were compared. GhMADS3 expressed in the wild type cotton flower primarily in stamens and carpels, which was comparable to AG in Arabidopsis. However, it was not expressed in floral buds of a homeotic cotton variant chvl. Ectopic expression of GhMADS3 in tobacco （Nicotiana tabacum L.） resulted in flowers with sepal-to-carpel and petal-to-stamen transformation. The carpelloid first whorl organs, with stigmatic tissue on their upper edges, had a white appearance when compared with the dark green color of the wild type sepals. At times, long filaments were observed at the fusion site of the first carpelloid oranges. The second whorl organs in staminoid were usually smaller than the wild type and the color was changed from pink to white. These results suggest that GhMADS3 has a homeotic role in flower development.
基金This work was supported by National Natural Sciences Foundation of China (No. 30160015).
文摘Sequences from the mitochondrial cytochrome b gene （Cyt b） were determined for 25 species from the superfamily Acridoidae and the homologous sequences of 19 species of grasshoppers were downloaded from the GenBank data library. The purpose was to develop a molecular phylogeny of the Acrypteridae, and to interpret the phylogenetic position of the family within the superfamily Acridoidea. Phylogeny was reconstructed by Maximum-parsimony （MP） and Bayesian criteria using Yunnanites coriacea and Tagasta marginella as outgroups. The alignment length of the fragments was 384 bp after excluding ambiguous sites, including 167 parsimony informative sites. In the fragments, the percentages of A ＋ T and G ＋ C were 70.7% and 29.3%, respectively. The monophyly of Arcypteridae is not supported by phylogenetic trees. Within the Arcypteridae, neither Arcypterinae nor Ceracrinae is supported as a monophyletic group. The current genus Chorthippus is not a monophyletic group, and should be a polyphyletic group. The present results are significantly different from the classification scheme of Arcypteridae, which is based on morphology.
基金Science and Technology Development Plan Project of Hangzhou,No.20201203B56.
文摘BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles in various cancers by influencing cell proliferation,invasion,and metastasis.AIM To analyze PEA3 subfamily gene expression levels in CCA and their correlation with clinical parameters to determine their prognostic value for CCA.METHODS The expression levels of PEA3 subfamily genes in pan-cancer and CCA data in the cancer genome atlas and genotype-tissue expression project databases were analyzed with R language software.Survival curve and receiver operating characteristic analyses were performed using the SurvMiner,Survival,and Procr language packages.The gene expression profiling interactive analysis 2.0 database was used to analyze the expression levels of PEA3 subfamily genes in different subtypes and stages of CCA.Web Gestalt was used to perform the gene ontology/Kyoto encyclopedia of genes and genomes(GO/KEGG)analysis,and STRING database analysis was used to determine the genes and proteins related to PEA3 subfamily genes.RESULTS ETV1,ETV4,and ETV5 expression levels were significantly increased in CCA.There were significant differences in ETV1,ETV4,and ETV5 expression levels among the different subtypes of CCA,and predictive analysis revealed that only high ETV1 and ETV4 expression levels were significantly associated with shorter overall survival in patients with CCA.GO/KEGG analysis revealed that PEA3 subfamily genes were closely related to transcriptional misregulation in cancer.In vitro and in vivo experiments revealed that PEA3 silencing inhibited the invasion and metastasis of CCA cells.CONCLUSION The expression level of ETV4 may be a predictive biomarker of survival in patients with CCA.
基金supported by the National Natural Science Foundation of China(No.30971244)
文摘Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracellular cholesterol in the foam ceils derived from rat VSMCs （rVSMCs） and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 （ABCA1）, adenosine triphosphate-binding cassette subfamily G member 1 （ABCG1） and peroxisome proliferator-activated receptor gamma （PPARy）. The rVSMCs were co-cultured with oxi- dized low density lipoprotein （LDL, 80 ~tg/mL） to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers （20, 40 and 60 pfu/cell） of recombinant adenovirus containing Mfn2 gene （Adv-Mfn2） were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group （P〈0.05）, and the ex- pression levels significantly increased when the titer of Adv-Mfn2 increased （P〈0.05）. At 24 or 48 h af- ter oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased （P〈0.05）, but it was sig- nificantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）, and it also significantly decreased when the titer of Adv-Mfn2 increased （P〈0.05）. The mRNA and pro- tein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. Though the mRNA and protein
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3Scientific Research Foundation of Shanxi Province of China for the Returned Overseas Chinese Scholars,No.2013011054-2
文摘The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.
基金Supported by The Science and Technology Planning Projects of Guizhou Province and Zunyi City,No.QKHJCZK[2022]YB642,No.ZSKH·HZ(2022)344,No.gzwjkj2021-071,ZMC·YZ[2018]38,No.ZSKH·HZ[2021]58,and No.ZSKH·HZ[2021]60The General Project of Hubei Province and Jingmen City,No.2021YFYB074.
文摘BACKGROUND Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery.However,some patients may develop postope-rative complications,liver failure,and other life-threatening situations.Here,we report a patient with mutations in the uridine 5’-diphospho-glucuronosyltrans-ferase 1A1(UGT1A1)and bile salt export pump(adenosine triphosphate-binding cassette subfamily B member 11,ABCB11)genes who presented multiple intrahe-patic bile duct stones and cholestasis,and the jaundice of the patient increased after partial hepatectomy.CASE SUMMARY A 52-year-old male patient admitted to the hospital on October 23,2021,with a progressive exacerbation of jaundice,was found to have multiple intrahepatic bile duct stones with the diagnoses of obstructive jaundice and acute cholecystitis.Subsequently,the patient underwent left hepatectomy with biliary exploration,stone extraction,T-tube drainage,and cholecystectomy without developing any intraoperative complications.The patient had a dark urine color with worsening jaundice postoperatively and did not respond well to plasma exchange and other symptomatic and supportive treatments.Since the progressive increase in postoperative bilirubin could not be clinically explained with any potential reason,including,if not at all,viral infection,cholangitis,autoimmune liver disease,and other causes,the patient underwent whole-exon screening for any genetic diseases,which surprisingly identified UGT1A1 and ABCB11 gene mutations related to glucuronidation of indirect bilirubin as well as bile acid transport in hepatocytes,respectively.Thus,we hypothesized that postoperative refractory cholestasis might result from UGT1A1 and ABCB11 gene mutations and further recommended liver transplantation to the patient,who eventually declined it and died from liver failure six months later.CONCLUSION Surgery may aggravate cholestasis in patients with multiple intrahepatic bile duct stones and cholestasis associated with UGT1A1 and ABCB11 gene mutations
基金This study was supported by Chinese National Programs for High Technology Research and Development （863 Project ） （No 2002AA242011）National Natural Science Foundation of China （No. 30571323）China Scholarship Council and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Yangzhou University.
文摘A total of 321 individuals from six cattle populations of four species in a bovine subfamily in China were studied using 12 pairs of microsatellite markers. The genetic diversities within and between populations were calculated. The phylogenetic trees were constructed by （δμ）^2 and DA distances, and the divergence times between populations were estimated by （δμ）^2. Altogether, 144 microsatellite alleles were detected including 24 private alleles and nine shared alleles. Chinese Holstein had the largest number of private alleles （10）, whereas Bohai black and Buffalo had the smallest number of private alleles （2）. Chinese Holstein showed the highest genetic variability. Its observed number of alleles （Na）, mean effective number of alleles （MNA）, and mean heterozygosity （He） were 7.7500, 4.9722, and 0.7719, respectively, whereas, the Buffalo and Yak showed low genetic variability. In the phylogenetic trees, Luxi and Holstein grouped first, followed by Bohai and Minnan. Yak branched next and buffalo emerged as the most divergent population from other cattle populations. Luxi and Bohai were estimated to have diverged 0.039-0.105 million years ago （MYA）, however, buffalo and Holstein diverged 0.501-1.337 MYA. The divergence time of Yak versus Minnan, Holstein and buffalo was 0.136-0.363, 0.273-0.729, and 0.326-0.600 MYA, respectively.
基金the National Natural Science Foundation of China(No.81660757 and No.81303237)the Academic and Technological Foregoer Funds of Jiangxi Province,China(No.20162BCB22015)+3 种基金the Project on Cultivation of Medical Elite(Gan Po Ying Cai 555)(2013296)the Youth Science Funds of Jiangxi Province,China(No.20153BCB23019)the National Natural Science Foundation of Jiangxi Province(No.20161ACB21020)the Natural Science Research Project of Huaian(No.HAB201716)。
文摘OBJECTIVE:To investigate the antagonistic effect of the extract of Baizhu(Rhizoma Atractylodis Macrocephalae)(RAM)on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica(NUX)and propose the mechanism of these effects.METHODS:The apparent permeability value(Papp)and absorption rate constant(Ka)were chosen as indices.The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine.To confirm the results,the brucine and strychnine concentrations in hepatic portal venous blood were determined.Western blotting was used to study P-glycoprotein(P-gp)expression in the Caco-2 cell line.RESULTS:Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor,but no significant increase was noted in the presence of a tight junction regulator.The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression.CONCLUSION:The primary absorption mechanism for brucine and strychnine is passive transport,which is affected by P-gp.
基金the National Swedish Research Council(grants No.2015-04402,2019-04486)the Carl Trygger Foundation(CTS 20:6)+3 种基金the Jornvall FoundationJulian Francis for financial supportthe National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory,the Knut and Alice Wallenberg Foundationthe Research/Scientific Computing teams at The James Hutton Institute and NIAB for providing computational resources and technical support for the"UK's Crop Diversity Bioinformatics HPC"(BBSRC grant BB/S019669/1)。
文摘The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.
基金supported by the National Key R&D Program of China(2018YFA0901700)the Natural Science Foundation of Jiangsu Province(BK20202002)the Postgraduate Research and Practice Innovation Program of Jiangsu Province(KYCX18_1789).
文摘Betulinic acid(BA),a penta-cyclic triterpenoid found as a ubiquitous secondary metabolite throughout the plant kingdom,has aroused tremendous interests due to its different pharmacological properties,which lead to large market demand.However,the content of BA in plant is low for phytoextraction.Although chemical semi-synthesis or biotransformation of BA from betulin with high conversion efficiency is achieved,it still relies on phytoextraction from the bark of medicinal trees.To circumvent this issue,the biotechnological synthesis of BA in engineered yeasts has been developed.In this review,the pharmacological properties of BA are first summarized,including antitumor,anti-HIV,antiprotozoal,anti-inflammatory,apoptosis activator and anti-metabolic syndrome.Then,the traditional phytoextraction,semi-synthesis and biotechnological synthesis of BA are discussed.Particularly,current advances in its biotechnological synthesis and strategies to improve BA production are focused.Moreover,potential strategies for further promotion of BA yield,including the introduction of artificial isopentenol utilization pathway,semi-rational mutagenesis of lupeol synthase and cytochrome P450,and subcellular morphology and compartmentalization,are discussed.
基金supported by the China Postdoctoral Science Foundation Funded Project(Project No.:2019M662304).
文摘Objective:Due to the characteristics of insidious onset and early metastasis of pancreatic cancer(PC),patients are often diag-nosed at an advanced stage and often delayed in completing surgical resection timely,resulting in poor prognosis.Therefore,this study aims to explore the expression of potassium voltage-gated channel subfamily H member 2(KCNH2)in PC and its relation-ship with clinicopathological parameters and the related mechanisms.Methods:GEPIA database and immunohistochemical staining were used to analyze the difference in KCNH2 expression be-tween PC and adjacent tissue in RNA and protein levels.Chi-squared test was used to evaluate the relationship between KCNH2 expression and clinicopathological features.The Cox regression model was used for multivariate analysis and univariate analysis.Histological diagnosis was performed according to World Health Organization(WHO)criteria to evaluate the relationship between KCNH2 expression and clinicopathological features.Results:KCNH2 expression was upregulated in PC compared with normal pancreatic tissue.In addition,the knockdown of KCNH2 inhibits PC cell proliferation,migration,invasion,and epithelial-mesenchymal transformation and promotes their apopto-sis.In addition,clinical data showed that the abnormal expression of KCNH2 in PC was related to the tumor stage.Patients with high expression of KCNH2 had a poor prognosis.Conclusions:KCNH2 is expected to be a novel targeted molecule in treating PC.
