Background: Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accum...Background: Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs(lnc RNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. Data sources: We carried out a systematic review on lnc RNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lnc RNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in Pub Med with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lnc RNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. Results: Lnc RNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting mi RNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. Conclusions: The functional lnc RNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.展开更多
Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate(cis-(±)-1)is an attractive route for the synthesis of(S,S)-2,8-diazobicyclo[4.3.0]nonane,an important chir...Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate(cis-(±)-1)is an attractive route for the synthesis of(S,S)-2,8-diazobicyclo[4.3.0]nonane,an important chiral intermediate of the fluoroquinolone antibiotic,moxifloxacin.In our previous study,a lipase from Sporisorium reilianum(SRL)was identified to possess excellent thermostability and pH stability.However,the low enzymatic activity of the SRL is a challenge that must be addressed.A rational design was initially employed for SRL tailoring according to the engineered Candida antarctica lipase B(CALB),resulting in a beneficial variant called SRL-I194N/V195L.Subsequently,two key amino acid residues in loop 6,L145 and L154,which might modulate the lid conformation between open and closed,were identified.A tetra-site variant,SRL-I194N/V195L/L145V/L154G(V13),with a significantly enhanced activity of 87.8 U∙mg^(−1) was obtained;this value was 2195-fold higher than that of wild-type SRL.Variant V13 was used to prepare optically pure(2S,3R)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate((2S,3R)-1),resolving 1 mol∙L^(−1) cis-(±)-1 with a conversion of 49.9%in 2 h and absolute stereoselectivity(E>200).Excellent stability with a half-life of 92.5 h was also observed at 50℃.Overall,the study findings reveal a lipase with high activity toward cis-(±)-1 at an industrial level and may offer a general strategy for enhancing the enzyme activity of other lipases and other classes of enzymes with a lid moiety.展开更多
R2(4hydroxyphenoxy)propionic acid(RHPPA)is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed.The main route for RHPPA biosynthesis is to hydroxylate the substrate R2p...R2(4hydroxyphenoxy)propionic acid(RHPPA)is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed.The main route for RHPPA biosynthesis is to hydroxylate the substrate R2phenoxypropionic acid(RPPA)at C4 position with microbes.In order to provide sufficient RPPA for the industrial production of RHPPA,an effective RPPA synthesis method was established and optimized in this work.The synthesis process mainly consisted of two steps:(1)synthesis of S2chloropropionic acid from Lalanine via diazotization and chlorination reactions;and(2)synthesis of RPPA from S2chloropropionic acid and phenol via etherification reaction.The optimal reaction conditions were as follows:HCl:NaNO_(2):KI:LAla=2.0:1.2:0.7:1.0(in molar),125℃reflux for 1.5 h,with KI as catalyst,and KI:S2chloropropionic acid:phenol=0.075:1.2:1.0(in molar).Under these conditions,an improved molar conversion rate(74.9%,calculated in phenol)was achieved.After extraction using anionic exchange resin Amberlite IRA400(CI),RPPA product with a purity of 95.08%was obtained.The purified RPPA was identified and evaluated in the application of the biotransformative production of RHPPA.The results indicated that the synthesized RPPA supported the RHPPA biosynthesis with a comparable yield as that of the standard RPPA.The RPPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials,less toxicity of reagents,simple manipulations,and low equipment/instrument requirements.展开更多
Catenated cages are generally considered thermodynamically more stable than their constituent monomeric cages.However,the catenation mechanism is yet to be elucidated;it would require systematic investigation into the...Catenated cages are generally considered thermodynamically more stable than their constituent monomeric cages.However,the catenation mechanism is yet to be elucidated;it would require systematic investigation into the structural effects of the building blocks,their enthalpic and entropic contributions,and the effect of solvents.By inspecting these factors,we rationalized some design principles for the efficient construction of catenated cages.展开更多
基金supported by grants from the Scientific Research Fund of National Health Commission of China-Key Health Science and Technology Program of Zhejiang Province (WKJ-ZJ-2201)the Key Project of Social Welfare Program of Zhejiang Science and Technology Department,“Lingyan” Program (2022C03099)。
文摘Background: Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs(lnc RNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. Data sources: We carried out a systematic review on lnc RNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lnc RNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in Pub Med with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lnc RNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. Results: Lnc RNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting mi RNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. Conclusions: The functional lnc RNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.
基金This work was financially supported by the National Key Research and Development Program of China(2021YFC2102100 and 2018YFA0901400)the Fundamental Research Funds for the Provincial Universities of Zhejiang(RF-C2019005)+1 种基金the National Natural Science Foundation of China(32000898)the Natural Science Foundation of Zhejiang Province(LQ21B060006).
文摘Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate(cis-(±)-1)is an attractive route for the synthesis of(S,S)-2,8-diazobicyclo[4.3.0]nonane,an important chiral intermediate of the fluoroquinolone antibiotic,moxifloxacin.In our previous study,a lipase from Sporisorium reilianum(SRL)was identified to possess excellent thermostability and pH stability.However,the low enzymatic activity of the SRL is a challenge that must be addressed.A rational design was initially employed for SRL tailoring according to the engineered Candida antarctica lipase B(CALB),resulting in a beneficial variant called SRL-I194N/V195L.Subsequently,two key amino acid residues in loop 6,L145 and L154,which might modulate the lid conformation between open and closed,were identified.A tetra-site variant,SRL-I194N/V195L/L145V/L154G(V13),with a significantly enhanced activity of 87.8 U∙mg^(−1) was obtained;this value was 2195-fold higher than that of wild-type SRL.Variant V13 was used to prepare optically pure(2S,3R)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate((2S,3R)-1),resolving 1 mol∙L^(−1) cis-(±)-1 with a conversion of 49.9%in 2 h and absolute stereoselectivity(E>200).Excellent stability with a half-life of 92.5 h was also observed at 50℃.Overall,the study findings reveal a lipase with high activity toward cis-(±)-1 at an industrial level and may offer a general strategy for enhancing the enzyme activity of other lipases and other classes of enzymes with a lid moiety.
文摘R2(4hydroxyphenoxy)propionic acid(RHPPA)is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed.The main route for RHPPA biosynthesis is to hydroxylate the substrate R2phenoxypropionic acid(RPPA)at C4 position with microbes.In order to provide sufficient RPPA for the industrial production of RHPPA,an effective RPPA synthesis method was established and optimized in this work.The synthesis process mainly consisted of two steps:(1)synthesis of S2chloropropionic acid from Lalanine via diazotization and chlorination reactions;and(2)synthesis of RPPA from S2chloropropionic acid and phenol via etherification reaction.The optimal reaction conditions were as follows:HCl:NaNO_(2):KI:LAla=2.0:1.2:0.7:1.0(in molar),125℃reflux for 1.5 h,with KI as catalyst,and KI:S2chloropropionic acid:phenol=0.075:1.2:1.0(in molar).Under these conditions,an improved molar conversion rate(74.9%,calculated in phenol)was achieved.After extraction using anionic exchange resin Amberlite IRA400(CI),RPPA product with a purity of 95.08%was obtained.The purified RPPA was identified and evaluated in the application of the biotransformative production of RHPPA.The results indicated that the synthesized RPPA supported the RHPPA biosynthesis with a comparable yield as that of the standard RPPA.The RPPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials,less toxicity of reagents,simple manipulations,and low equipment/instrument requirements.
基金supported by the National Natural Science Foundation of China(key program 21890733)and the Shanghai Natural Science Foundation(no.18ZR1420800).
文摘Catenated cages are generally considered thermodynamically more stable than their constituent monomeric cages.However,the catenation mechanism is yet to be elucidated;it would require systematic investigation into the structural effects of the building blocks,their enthalpic and entropic contributions,and the effect of solvents.By inspecting these factors,we rationalized some design principles for the efficient construction of catenated cages.