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Yingying Lin,1,* Xiaoyan Xiu,2,* Juan Lin,3 Zhiwei Chen,3 Cui Xian Zheng,3 Xuehong Pan,2 Lihua Lin,1 Jianying Yan3 1Department of Healthcare, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Health Education, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianying Yan, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China, Tel +86591-86329270, Email fjsfyyan@126.comBackground: The goal is to evaluate the effects of a flipped class strategy on knowledge, self-directed learning ability, learning satisfaction and pregnancy outcomes in primiparas undergoing antenatal education.Methods: A random sampling method was adopted. A total of 600 primiparas who were diagnosed with early pregnancy in a first-class hospital in southeast China and received continuous prenatal health education from May to July 2020 were selected as the research subjects. In order to make the baseline of the two groups of primipara comparable, we divided the two groups in the antenatal education centre according to the odd-even number of the lesson card number. The odd-numbered group was the experimental group, who used the prenatal health education model based on blended learning; the even-numbered group was the control group, who used the traditional mode of prenatal

The rapid development of biogas plants in China has generated large quantities of digestate. The disparity between the continuity of biogas plant operation and the seasonality of digestate utilization has led to the need to store digestate. Therefore, untargeted profiling of bioactive compounds in the digestate stored under aerobic and anaerobic conditions was performed. The antioxidant and antifungal activity of digestate stored under varying conditions was likewise assessed. The results delineated that digestate storage under varying conditions brought about the degradation of organic acids, alkenes, aldehydes, alcohols, ketones, ethers, amino acids and their derivatives, and esters, leading to the stabilization of digestate components. Together, these new data revealed that digestate storage for up to 20 days under aerobic conditions promotes glycine, serine, and threonine degradation pathways and enhances biotin and vitamins production. In contrast, anaerobic storage enhances the taurine and hypotaurine metabolic pathways and increases the derivation of antimicrobial substances, such as indole alkaloids. Moreover, digestate storage under anaerobic conditions promotes antioxidant and antifungal activity more than storage under aerobic conditions. These findings can contribute to the future development of high-value agricultural products from digestate and the sustainability of biogas plants. Further studies are required for the untargeted metabolomic of digestate under storage to explore the underlying mechanisms of promoting disease resistance by the digestate upon land application.

Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

One new imidazole derivative alkaloid pelopuradazole (1), together with three known alkaloids as in 3H-imidazole-4-carboxylic acid (2), 1H-pyrrole-2-carboxylic acid (3) and 2-methyl-3H-imidazole-4-carboxylic acid (4) and two known cyclo-dipeptides pelopurin A (5) and pelopurin B (6), has been isolated from the marine bacterium Pelomonas puraquae sp. nov. Pelopuradazole (1) was a new imidazole derivative alkaloid, while compounds 2, 3, 5 and 6 were firstly obtained as natural products. Compounds 1–6 were isolated from P. puraquae sp. nov. for the first time.

One new imidazole derivative alkaloid pelopuradazole (1), together with three known alkaloids as in 3H-imidazole-4-carboxylic acid (2), 1H-pyrrole-2-carboxylic acid (3) and 2-methyl-3H-imidazole-4-carboxylic acid (4) and two known cyclo-dipeptides pelopurin A (5) and pelopurin B (6), has been isolated from the marine bacterium Pelomonas puraquae sp. nov. Pelopuradazole (1) was a new imidazole derivative alkaloid, while compounds 2, 3, 5 and 6 were firstly obtained as natural products. Compounds 1–6 were isolated from P. puraquae sp. nov. for the first time.

A number of carcinogens or their electrophilic intermediates are able to bind covalently to DNA, forming DNA adducts. DNA adducts may cause gene mutations if they are misrepaired or remain unrepaired before DNA replication occurs. DNA adduct formation is believed to be the initial step of chemical carcinogenesis. 2-Nitrofluorene (NF) is an air pollutant and a carcinogen. Metabolism of NF is generally via nitro-reductive and oxidative pathways. Nitro-reductive metabolism of NF results in formation of 2-aminofluorene and 2-acetylaminofluorene, two well known carcinogens. The present study focused on investigating DNA adducts and carcinogenesis using NF and some of its derivatives as model substances. The nitro function is supposed to be crucial for the genotoxic effects of nitroarenes. However, the great difference between NF and 2,7-dinitrofluorene (2,7-dNF) in the Salmonella mutagenicity test was not seen in the in vivo genotoxic assays. After intraperitoneal or oral administration, 2,7-dNF induced a lower amount of DNA adducts and a similar or higher amount of preneoplastic lesions in the liver compared to NF. Oral administration of NF or 2,7-dNF induced a higher amount of DNA adducts and preneoplastic liver lesions than intraperitoneal injection. The genotoxicity of oxidized metabolites of NF, 5-, 7- and 9-OH-NF, was studied in vitro and in vivo. Generally, capacity of these substances to initiate preneoplastic liver lesions was associated with their potential to form DNA adducts. 5-OH-NF showed low or no potential to induce DNA adduct formation and preneoplastic liver lesions. 7- and 9-OH-NF induced less DNA adducts and preneoplastic liver lesions than NF. The long-term tumor study showed that NF was a potent carcinogen, primarily targeting the liver, forestomach and kidney. NF induced tumor development and DNA adduct formation in a dose-dependent manner. The levels of DNA adducts in different organs during NF administration were associated with the location of t

A number of carcinogens or their electrophilic intermediates are able to bind covalently to DNA, forming DNA adducts. DNA adducts may cause gene mutations if they are misrepaired or remain unrepaired before DNA replication occurs. DNA adduct formation is believed to be the initial step of chemical carcinogenesis. 2-Nitrofluorene (NF) is an air pollutant and a carcinogen. Metabolism of NF is generally via nitro-reductive and oxidative pathways. Nitro-reductive metabolism of NF results in formation of 2-aminofluorene and 2-acetylaminofluorene, two well known carcinogens. The present study focused on investigating DNA adducts and carcinogenesis using NF and some of its derivatives as model substances. The nitro function is supposed to be crucial for the genotoxic effects of nitroarenes. However, the great difference between NF and 2,7-dinitrofluorene (2,7-dNF) in the Salmonella mutagenicity test was not seen in the in vivo genotoxic assays. After intraperitoneal or oral administration, 2,7-dNF induced a lower amount of DNA adducts and a similar or higher amount of preneoplastic lesions in the liver compared to NF. Oral administration of NF or 2,7-dNF induced a higher amount of DNA adducts and preneoplastic liver lesions than intraperitoneal injection. The genotoxicity of oxidized metabolites of NF, 5-, 7- and 9-OH-NF, was studied in vitro and in vivo. Generally, capacity of these substances to initiate preneoplastic liver lesions was associated with their potential to form DNA adducts. 5-OH-NF showed low or no potential to induce DNA adduct formation and preneoplastic liver lesions. 7- and 9-OH-NF induced less DNA adducts and preneoplastic liver lesions than NF. The long-term tumor study showed that NF was a potent carcinogen, primarily targeting the liver, forestomach and kidney. NF induced tumor development and DNA adduct formation in a dose-dependent manner. The levels of DNA adducts in different organs during NF administration were associated with the location of t

A number of carcinogens or their electrophilic intermediates are able to bind covalently to DNA, forming DNA adducts. DNA adducts may cause gene mutations if they are misrepaired or remain unrepaired before DNA replication occurs. DNA adduct formation is believed to be the initial step of chemical carcinogenesis. 2-Nitrofluorene (NF) is an air pollutant and a carcinogen. Metabolism of NF is generally via nitro-reductive and oxidative pathways. Nitro-reductive metabolism of NF results in formation of 2-aminofluorene and 2-acetylaminofluorene, two well known carcinogens. The present study focused on investigating DNA adducts and carcinogenesis using NF and some of its derivatives as model substances. The nitro function is supposed to be crucial for the genotoxic effects of nitroarenes. However, the great difference between NF and 2,7-dinitrofluorene (2,7-dNF) in the Salmonella mutagenicity test was not seen in the in vivo genotoxic assays. After intraperitoneal or oral administration, 2,7-dNF induced a lower amount of DNA adducts and a similar or higher amount of preneoplastic lesions in the liver compared to NF. Oral administration of NF or 2,7-dNF induced a higher amount of DNA adducts and preneoplastic liver lesions than intraperitoneal injection. The genotoxicity of oxidized metabolites of NF, 5-, 7- and 9-OH-NF, was studied in vitro and in vivo. Generally, capacity of these substances to initiate preneoplastic liver lesions was associated with their potential to form DNA adducts. 5-OH-NF showed low or no potential to induce DNA adduct formation and preneoplastic liver lesions. 7- and 9-OH-NF induced less DNA adducts and preneoplastic liver lesions than NF. The long-term tumor study showed that NF was a potent carcinogen, primarily targeting the liver, forestomach and kidney. NF induced tumor development and DNA adduct formation in a dose-dependent manner. The levels of DNA adducts in different organs during NF administration were associated with the location of t

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