Skipped dienes are of great importance but remain challenging to synthesize because of the presence of a sp hybrid carbon between the two alkenes.Herein,we have developed the first nickel-catalyzed regio-,(E)-stereo-a...Skipped dienes are of great importance but remain challenging to synthesize because of the presence of a sp hybrid carbon between the two alkenes.Herein,we have developed the first nickel-catalyzed regio-,(E)-stereo-and linear-selective ring-opening/cross-coupling reaction of vinylaziridines with organoboronic acids under mild conditions to construct various skipped aminodienes.The reaction exhibits wide functional-group compatibility,and could be adapted for the introduction of skipped aminodiene functionality into bioactive molecules.展开更多
CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozy...CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozygous mutants of the insulin receptor gene 2(NlInR2)in the brown planthopper(Nilaparvata lugens)using CRISPR/Cas9 genome editing.Both frameshift mutants,E5_D17 and E6_I7,differentiated towards long wings,but there were differences in wing morphology,with E5_D17 showing wing deformities.Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants,as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17.Additionally,the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein.RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%,suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions.Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.展开更多
Colorectal cancer(CRC)is a prevalent malignant tumor,with the global new cases reaching 1.9316 million and deaths reaching 935,200 in 2022.In China,therewere 555,500 new cases of CRC,with an age-standardized incidence...Colorectal cancer(CRC)is a prevalent malignant tumor,with the global new cases reaching 1.9316 million and deaths reaching 935,200 in 2022.In China,therewere 555,500 new cases of CRC,with an age-standardized incidence rate of 24.07 per 10million,and 286,200 deaths.China accounts for approximately 30%of new cases and deaths from CRC worldwide,with East Asia accounting for over 75%.Initially,CRC presents as local tumor growth,but it has the potential to spread to other body parts over time.Perineural infiltration(PNI)is a relatively less discussed route of diffusion,yet it plays a crucial role in the progression and prognosis of CRC.PNI often occurs alongside local lymph nodes and distant metastases,posing challenges for treatment and management.Clinical symptoms,radiographic findings,and histopathological examination can be used to diagnose PNI with skipmetastasis.Symptoms commonly include local pain,paresthesia,andmotor impairment.Imaging helps identify the mass’s location and relationship to nerves,whereas histopathological examination confirms the diagnosis.Treatment of PNI skipmetastases is similar to other CRC metastases,including surgical resection,chemotherapy,radiotherapy,and targeted therapy.Surgical resection is the primary therapeutic approach,but the wider range of metastasis in PNI skip transfer may limit its feasibility.In cases where surgical resection is not possible,chemotherapy,radiotherapy,and targeted therapy are used to control tumor metastasis.In conclusion,PNI skip metastases increase the risk of poor prognosis for CRC,requiring a comprehensive approach with multiple treatments to prevent disease progression.Early detection and treatment are vital to improving prognosis.展开更多
Skipped polyol is a common motif in numerous biologically significant polyketides and has been the focus of the development of novel synthetic methods and strategies. In this work, we devised a highly diastereoselecti...Skipped polyol is a common motif in numerous biologically significant polyketides and has been the focus of the development of novel synthetic methods and strategies. In this work, we devised a highly diastereoselective approach to access skipped triol(anti,syn-isomer) from a chiral α-allenic alcohol which was derived from kinetic resolution in our previous studies. An iodolactonization and subsequent radical deiodonation efficiently introduced the hydroxyl group at C3 in a highly diastereoselective manner and exemplified in enantioselective total synthesis of (+)-yashabushitriol.展开更多
Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora...Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237(MLN)and/or p21 depletion by small interfering RNA(si RNA).Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator(FUCCI)system combined with histone H3 phosphorylation at Ser10(p S10 H3)detection.Senescence was assessed using senescence-associated-β-galactosidase(SA-β-Gal),Ki67,andγH2AX staining.Protein expression levels were determined using western blotting.Results Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment.The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells,ultimately leading to senescence in G1.During this process,the p53/p21 pathway is hyperactivated.Accompanying p21 accumulation,Aurora A kinase levels declined sharply.MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.Conclusion Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation,leading to senescence via mitotic skipping.展开更多
Circuit design of 32 bit logarithmic skip adder (LSA) is introduced to implement high performance,low power addition.ELM carry lookahead adder is included into groups of carry skip adder and the hybrid structure cost...Circuit design of 32 bit logarithmic skip adder (LSA) is introduced to implement high performance,low power addition.ELM carry lookahead adder is included into groups of carry skip adder and the hybrid structure costs 30% less hardware than ELM.At circuit level,a carry incorporating structure to include the primary carry input in carry chain and an 'and xor' structure to implement final sum logic in 32 bit LSA are designed for better optimization.For 5V,1μm process,32 bit LSA has a critical delay of 5 9ns and costs an area of 0 62mm 2,power consumption of 23mW at 100MHz.For 2 5V,0 25μm process,critical delay of 0 8ns,power dissipation of 5 2mW at 100MHz is simulated.展开更多
基金the funding support of this work by the National Natural Science Foundation of China(Nos.21831005 and 21991112)National Key R&D Program of China(No.2018YFE0126800).
文摘Skipped dienes are of great importance but remain challenging to synthesize because of the presence of a sp hybrid carbon between the two alkenes.Herein,we have developed the first nickel-catalyzed regio-,(E)-stereo-and linear-selective ring-opening/cross-coupling reaction of vinylaziridines with organoboronic acids under mild conditions to construct various skipped aminodienes.The reaction exhibits wide functional-group compatibility,and could be adapted for the introduction of skipped aminodiene functionality into bioactive molecules.
基金the National Natural Science Foundation of China(31730073).
文摘CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozygous mutants of the insulin receptor gene 2(NlInR2)in the brown planthopper(Nilaparvata lugens)using CRISPR/Cas9 genome editing.Both frameshift mutants,E5_D17 and E6_I7,differentiated towards long wings,but there were differences in wing morphology,with E5_D17 showing wing deformities.Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants,as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17.Additionally,the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein.RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%,suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions.Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.
文摘Colorectal cancer(CRC)is a prevalent malignant tumor,with the global new cases reaching 1.9316 million and deaths reaching 935,200 in 2022.In China,therewere 555,500 new cases of CRC,with an age-standardized incidence rate of 24.07 per 10million,and 286,200 deaths.China accounts for approximately 30%of new cases and deaths from CRC worldwide,with East Asia accounting for over 75%.Initially,CRC presents as local tumor growth,but it has the potential to spread to other body parts over time.Perineural infiltration(PNI)is a relatively less discussed route of diffusion,yet it plays a crucial role in the progression and prognosis of CRC.PNI often occurs alongside local lymph nodes and distant metastases,posing challenges for treatment and management.Clinical symptoms,radiographic findings,and histopathological examination can be used to diagnose PNI with skipmetastasis.Symptoms commonly include local pain,paresthesia,andmotor impairment.Imaging helps identify the mass’s location and relationship to nerves,whereas histopathological examination confirms the diagnosis.Treatment of PNI skipmetastases is similar to other CRC metastases,including surgical resection,chemotherapy,radiotherapy,and targeted therapy.Surgical resection is the primary therapeutic approach,but the wider range of metastasis in PNI skip transfer may limit its feasibility.In cases where surgical resection is not possible,chemotherapy,radiotherapy,and targeted therapy are used to control tumor metastasis.In conclusion,PNI skip metastases increase the risk of poor prognosis for CRC,requiring a comprehensive approach with multiple treatments to prevent disease progression.Early detection and treatment are vital to improving prognosis.
基金This work was supported by the National Natural Science Foundation of China (21472186)the Shanghai Science and Technology Commission (15JC1400400)+1 种基金partially supported by the Ministry of Science and Technology (2011CB710800)Calvine Lai thanks the internship from ENSCL to conduct the summer research (June–August of 2013) in the Hong laboratory
文摘Skipped polyol is a common motif in numerous biologically significant polyketides and has been the focus of the development of novel synthetic methods and strategies. In this work, we devised a highly diastereoselective approach to access skipped triol(anti,syn-isomer) from a chiral α-allenic alcohol which was derived from kinetic resolution in our previous studies. An iodolactonization and subsequent radical deiodonation efficiently introduced the hydroxyl group at C3 in a highly diastereoselective manner and exemplified in enantioselective total synthesis of (+)-yashabushitriol.
基金supported by the Science and Technology Research Project of Gansu Province[20JR5RA555 and145RTSA012]the Natural Science Foundation of Shaanxi Province[2020JQ-541]+1 种基金the National Natural Science Foundation of China[31870851 and 12175289]the Youth Innovation Promotion Association CAS[2021415]
文摘Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237(MLN)and/or p21 depletion by small interfering RNA(si RNA).Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator(FUCCI)system combined with histone H3 phosphorylation at Ser10(p S10 H3)detection.Senescence was assessed using senescence-associated-β-galactosidase(SA-β-Gal),Ki67,andγH2AX staining.Protein expression levels were determined using western blotting.Results Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment.The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells,ultimately leading to senescence in G1.During this process,the p53/p21 pathway is hyperactivated.Accompanying p21 accumulation,Aurora A kinase levels declined sharply.MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.Conclusion Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation,leading to senescence via mitotic skipping.
文摘Circuit design of 32 bit logarithmic skip adder (LSA) is introduced to implement high performance,low power addition.ELM carry lookahead adder is included into groups of carry skip adder and the hybrid structure costs 30% less hardware than ELM.At circuit level,a carry incorporating structure to include the primary carry input in carry chain and an 'and xor' structure to implement final sum logic in 32 bit LSA are designed for better optimization.For 5V,1μm process,32 bit LSA has a critical delay of 5 9ns and costs an area of 0 62mm 2,power consumption of 23mW at 100MHz.For 2 5V,0 25μm process,critical delay of 0 8ns,power dissipation of 5 2mW at 100MHz is simulated.
