ABSTRACT
Organocatalyzed diastereo- and enantioselective [3 + 2] cycloaddition reactions of donor-acceptor (D-A) cyclopropanes with isatin-derived ketimines are presented. Different from well-developed Lewis acid activation protocols which promote the reactivity of D-A cyclopropanes through coordinating to the acceptor group, in this reaction, dicyanocyclopropylmethyl ketones can be activated through nucleophilic activation of the donor group by using dihydroquinine-derived squaramide as Brønsted base catalyst. The reaction affords functionalized spiro[oxindole-3,2'-pyrrolidines] with two nonadjacent tetra- and tri-substituted stereocenters in 83-99% yields, moderate to excellent diastereoselectivities (up to >20:1 diastereomeric ratio (dr)), and excellent enantioselectivities (up to >99% enantiomeric excess (ee)) under mild conditions.
ABSTRACT
Polyradical cages are of great interest because they show very fascinating physical and chemical properties, but many challenges remain, especially for their synthesis and characterization. Herein, we present the synthesis of a polyradical cation cage 14â + through post-synthetic oxidation of a redox-active phenothiazine-based Pd2L4-type coordination cage 1. It's worth noting that 1 exhibits excellent reversible electrochemical and chemical redox activity due to the introduction of a bulky 3,5-di-tert-butyl-4-methoxyphenyl substituent. The generation of 14â + through reversible electrochemical oxidation is investigated by in situ UV/Vis-NIR and EPR spectroelectrochemistry. Meanwhile, chemical oxidation of 1 can also produce 14â + which can be reversibly reduced back to the original cage 1, and the process is monitored by EPR and NMR spectroscopies. Eventually, we succeed in the isolation and single crystal X-ray diffraction analysis of 14â +, whose electronic structure and conformation are distinct to original 1. The magnetic susceptibility measurements indicate the predominantly antiferromagnetic interactions between the four phenothiazine radical cations in 14â +. We believe that our study including the facile synthesis methodology and in situ spectroelectrochemistry will shed some light on the synthesis and characterization of novel polyradical systems, opening more perspectives for developing functional supramolecular cages.
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Iron porphyrin carbenes (IPCs) have been extensively recognized as the reactive intermediates in various iron porphyrin-catalyzed carbene transfer reactions. While donor-acceptor diazo compounds have been frequently used for such transformations, the structures and reactivities of donor-acceptor IPCs are less explored. To date, no crystal structures of donor-acceptor IPC complexes have been reported, and therefore, the involvement of IPC intermediacy for such transformations lacks direct evidence. Here we report the synthesis and NMR characterization of several donor-acceptor IPC complexes from iron porphyrin and corresponding donor-acceptor diazo compounds. The X-ray crystal structure of an IPC complex derived from a morpholine-substituted diazo amide was obtained. The carbene transfer reactivities of those IPCs were tested by the N-H insertion reactions with aniline or morpholine as well as the three-component reaction with aniline and γ,δ-unsaturated α-keto ester based on electrophilic trapping of an ammonium ylide intermediate. Based on these results, IPCs were identified as the real intermediates for iron porphyrin-catalyzed carbene transfer reactions from donor-acceptor diazo compounds.
ABSTRACT
This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1ß, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1ß, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.
Subject(s)
Acute Lung Injury , Drugs, Chinese Herbal , Ginsenosides , Humans , Tumor Necrosis Factor-alpha , Caspase 3 , Matrix Metalloproteinase 9 , Interleukin-6 , Molecular Docking Simulation , Network Pharmacology , Reactive Oxygen Species , Tandem Mass Spectrometry , Acute Lung Injury/drug therapy , Acute Lung Injury/genetics , Capsules , RNA, Messenger , Drugs, Chinese Herbal/pharmacologyABSTRACT
In this work, a facile and versatile strategy for the synthesis of contorted polycyclic aromatic hydrocarbons (PAHs) starting from the functionalized pentacene was established. A series of novel PAHs 1-4 and their derivatives were synthesized through a simple two-step synthesis procedure involving an intramolecular reductive Friedel-Crafts cyclization of four newly synthesized pentacene aldehydes 5-8 as a key step. All the molecules were confirmed by single-crystal X-ray diffraction and their photophysical and electrochemical properties were studied in detail. Interestingly, the most striking feature of 1-4 is their highly contorted carbon structures and the accompanying helical chirality. In particular, the optical resolution of 2 was successfully achieved by chiral-phase HPLC, and the enantiomers were characterized by circular dichroism and circularly polarized luminescence spectroscopy. Despite the highly nonplanar conformations, these contorted PAHs exhibited emissive properties with moderate-to-good fluorescence quantum yields, implying the potential utility of this series PAHs as high-quality organic laser dyes. By using a self-assembly method with the help of epoxy resin, a bottle microlaser based on 3 a was successfully illustrated with a lasing wavelength of 567.8â nm at a threshold of 0.3â mJ/cm2 . We believe that this work will shed light on the chemical versatility of pentacene and its derivatives in the construction of novel functionalized PAHs.
ABSTRACT
OBJECTIVES: To investigate the levels of physical growth and neurodevelopment in preterm infants at the corrected age of 18-24 months. METHODS: The physical growth data and neurodevelopment data of 484 preterm infants at corrected age of 18-24 months were prospectively collected by a post-discharge follow-up system for preterm infants. The infants were regularly followed up in Shenzhen Bao'an Maternal and Child Health Hospital Affiliated to Jinan University from April 2018 to December 2021. The neurodevelopment was evaluated by the Children Neuropsychological and Behavioral Scale-Revision 2016. A total of 219 full-term infants served as controls. The infants were divided into groups (extremely preterm, very preterm, moderate late preterm, and full-term) based on gestational age, and the groups were compared in the levels of physical growth and neurodevelopment. RESULTS: Except that the moderate preterm group had a higher length-for-age Z-score than the full-term group (P=0.038), there was no significant difference in physical growth indicators between the preterm groups and the full-term group (P>0.05). Each preterm group had a significantly lower total developmental quotient (DQ) than the full-term group (P<0.05). Except for the social behavior domain, the DQ of other domains in the extremely preterm and very preterm groups was significantly lower than that in the full-term group (P<0.05). The <32 weeks preterm group had a significantly higher incidence rate of global developmental delay than the full-term group (16.7% vs 6.4%, P=0.012), and the incidence rate of global developmental delay tended to increase with the reduction in gestational age (P=0.026). CONCLUSIONS: Preterm infants can catch up with full-term infants in terms of physical growth at the corrected age of 18-24 months, but with a lower neurodevelopmental level than full-term infants. Neurodevelopment monitoring and early intervention should be taken seriously for preterm infants with a gestational age of <32 weeks.
Subject(s)
Aftercare , Infant, Premature , Infant , Child , Infant, Newborn , Humans , Child, Preschool , Patient Discharge , Gestational AgeABSTRACT
This study analyzed the main chemical components of Zhuru Decoction via ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS), and then predicted the mechanism of Zhuru Decoction in clearing heat, resolving phlegm, detoxifying, and treating vomiting and alcohol-related vomiting caused by heat in stomach based on network pharmacology. The gradient elution was conducted in Agilent ZORBAX extend-C_(18) column(2.1 mm×100 mm, 1.8 µm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 â. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the data were collected in the scanning range of m/z 100-1 500. A total of 98 compounds in Zhuru Decoction were identified via BATMAN, SYMMAP, TCMSP, and relevant literature, including 36 flavonoids, 7 triterpenoids, 8 gingerols, 20 organic acids, 5 amino acids, and 22 other compounds. On the basis of the available studies, 9 components were selected as index components, and the protein-protein interaction(PPI) network of the common targets was established with STRING 11.0. Finally, 10 core targets associated with the pharmacodynamic effect were screened out. This study established the UPLC-Q-TOF-MS/MS method for identifying the chemical components in the classic prescription Zhuru Decoction, and employed network pharmacology to explore the core targets of its efficacy, which provided a refe-rence for the quality control and the research of the pharmacodynamic substances of Zhuru Decoction.
Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Humans , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Network Pharmacology , VomitingABSTRACT
A total of 18 batches of Zhuru Decoction samples were prepared. Chromatographic fingerprints were established for Zhuru Decoction and single decoction pieces, the content of which was then determined. The extraction rate ranges, content, and transfer rate ranges of puerarin, liquiritin, and glycyrrhizic acid, together with the common peaks and the similarity range of the fingerprints, were determined to clarify key quality attributes of Zhuru Decoction. The 18 batches of Zhuru Decoction samples had 25 common peaks and the fingerprint similarity higher than 0.95. Puerariae Lobatae Radix, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens had 21, 3, and 1 characteristic peaks, respectively. The 18 batches of samples showed the extraction rates within the range of 18.45%-25.29%. Puerarin had the content of 2.20%-3.07% and the transfer rate of 38.5%-45.9%; liquiritin had the content of 0.24%-0.85% and the transfer rate of 15.9%-37.5%; glycyrrhizic acid had the content of 0.39%-1.87% and the transfer rate of 16.2%-32.8%. In this paper, the quality value transmitting of substance benchmarks of Zhuru Decoction was analyzed based on chromatographic fingerprints, extraction rate, and the content of index components. A scientific and stable method was preliminarily established, which provided a scientific basis for the quality control and formulation development of Zhuru Decoction.
Subject(s)
Drugs, Chinese Herbal , Quality Control , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/standards , Glycyrrhizic Acid/analysis , Rhizome/chemistryABSTRACT
Following the preparation of substance benchmarks in Huanglian Decoction from 18 batches, the method for detecting their characteristic spectra was established to identify the similarity range and peak attribution. The content and transfer rate ranges of the index components coptisine, palmatine, berberine, liquiritin, glycyrrhizic acid, 6-gingerol, and cinnamaldehyde and the extraction amount were combined for analyzing the quality value transfer from the Chinese medicinal pieces to substance benchmarks and clarifying the key quality attributes of substance benchmarks in Huanglian Decoction. The results showed that the substance benchmarks in Huang-lian Decoction of 18 batches exhibited good similarity in characteristic spectra(all greater than 0.98). There were 17 characteristic peaks identified in the substance benchmarks of Huanglian Decoction, including 10 from Coptidis Rhizoma, 3 from Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle(processed with water), 1 from Zingiberis Rhizoma, and 3 from Cinnamomi Ramulus. The contents and average transfer rates of the index components were listed as follows: coptisine 2.20-6.46 mg·g~(-1) and 18.50%±2.93%; palmatine 3.03-8.13 mg·g~(-1) and 26.56%±4.69%; berberine 7.71-22.29 mg·g~(-1) and 17.34%±3.00%; liquiritin 0.88-2.18 mg·g~(-1) and 9.88%±4.88%; glycyrrhizic acid 1.83-4.44 mg·g~(-1) and 8.50%±3.72%; 6-gingerol 0.56-1.43 mg·g~(-1) and 11.36%±2.37%; cinnamaldehyde 1.55-3.48 mg·g~(-1) and 19.02%±4.36%. The extraction amount of the substance benchmarks from the 18 batches was controlled at 10.65%-13.88%. In this paper, the quality value transfer of substance benchmarks in Huanglian Decoction was analyzed based on the characteristic spectra, the index component contents and the extraction amount, which has provided a basis for the subsequent development of Huanglian Decoction and the quality control of its related preparations.
Subject(s)
Drugs, Chinese Herbal , Quality Control , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/standardsABSTRACT
OBJECTIVES: To study the value of Silverman-Anderson score versus Downes score in predicting respiratory failure in full-term neonates. METHODS: The convenience sampling method was used to select the full-term neonates with lung diseases who were hospitalized in the neonatal intensive care unit from July 2020 to July 2021. According to the diagnostic criteria for neonatal respiratory failure, they were divided into a respiratory failure group (65 neonates) and a non-respiratory failure group (363 neonates). Silverman-Anderson score and Downes score were used for evaluation. The receiver operating characteristic analysis was used to compare the value of the two noninvasive scores in predicting respiratory failure in full-term neonates. RESULTS: Among the 428 full-term neonates, 65 (15.2%) had respiratory failure. The Silverman-Anderson score had a significantly shorter average time spent on evaluation than the Downes score [(90±8) seconds vs (150±13) seconds; P<0.001]. The respiratory failure group had significantly higher points in both the Silverman-Anderson and Downes scores than the non-respiratory failure group (P<0.001). The Silverman-Anderson score had an AUC of 0.876 for predicting respiratory failure, with a sensitivity of 0.908, a specificity of 0.694, and a Youden index of 0.602 at the optimal cut-off value of 4.50 points. The Downes score had an AUC of 0.918 for predicting respiratory failure, with a sensitivity of 0.723, a specificity of 0.953, and a Youden index of 0.676 at the optimal cut-off value of 6.00 points. The Downes score had significantly higher AUC for predicting respiratory failure than the Silverman-Anderson score (P=0.026). CONCLUSIONS: Both Silverman-Anderson and Downes scores can predict the risk of respiratory failure in full-term neonates. The Silverman-Anderson score requires a shorter time for evaluation, while the Downes score has higher prediction efficiency. It is recommended to use Downes score with higher prediction efficiency in general evaluation, and the Silverman-Anderson score requiring a shorter time for evaluation can be used in emergency.
Subject(s)
Intensive Care Units, Neonatal , Respiratory Insufficiency , Humans , Infant, Newborn , Prognosis , ROC Curve , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Risk FactorsABSTRACT
The topic of noncovalent spin-spin interactions is of increasing general interest in supramolecular radical chemistry. In this report, a series of exo- and endo-TEMPO radical-functionalized metallacycles 1-4 and metallacages 5 and 6 were constructed via coordination-driven self-assembly, wherein the number, location, and distance of the spins were precisely controlled. Their intriguing spin-spin interactions were systematically investigated by electron paramagnetic resonance (EPR) and were well interpreted at the molecular level assisted by X-ray crystallography analysis. The results revealed their distinct spin-spin interactions in the solution state, wherein the spin-spin interaction of metallacycle 3 was much stronger than that of the other five assemblies mainly due to its shorter intramolecular spin-spin distance. In the solid state, 1-6 exhibited obvious spin-spin (dipole-dipole) interactions because of the close arrangement of TEMPO units as indicated in their single crystals. Specifically, a large zero-field splitting (ZFS; D = 17.5 mT) was observed in the crystalline form of metallacycle 4, which arose from the strong intermolecular spin-spin coupling. Interestingly, when the counterion of PF6- in 4 was changed to BF4-, the BF4- counterion analog 4a also exhibited a large ZFS, but the ZFS originated from the intramolecular spin-spin interaction due to a small variation in its crystal conformation. Moreover, the reversible on-off switching of the ZFS in 4 and 4a via the crystal-to-amorphous transformation induced by mechanical grinding and solvent vapor stimuli was also successfully realized. The unique and controllable inter- and intramolecular spin-spin interactions in this work reveal new insights for the understanding and manipulation of spin-spin interactions and may open up a new way to develop organic spin materials in the future.
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TANK-binding kinase 1 (TBK1) belongs to the noncanonical IκB kinase (IKK) family. The ubiquitously expressed protein is well known to play a pivotal role in innate immune response and inflammation. Although excessive inflammatory activities have been shown to affect osteoclast (OC) differentiation and function, direct relevance of TBK1 in bone turnover is not known. In this work, we specifically altered the TBK1 protein level by knocking down or overexpressing it without affecting its homologous protein IKKε expression, and demonstrated the effect of TBK1 on OC differentiation in bone marrow macrophages (BMMs) and RAW264.7 cells upon induction by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). TBK1 knockdown was found to markedly inhibit the OC differentiation and function, while TBK1 overexpression enhanced OC formation. Downregulation of TBK1 greatly suppressed RANKL-induced gene expression of Mmp9, Atp6v0d2, Acp5, Ctsk andNfatc1 involved in the regulation of OC formation and function in both BMM and RAW264.7 cells. Mechanistic studies indicated that TBK1 affected the NF-κB signaling pathway as well as mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) activation during OC differentiation. Moreover, the protein level of TNF receptor-associated factor 6 (TRAF6) was increased, and the interaction of TRAF6 with TBK1 was potentiated, by RANKL. Collectively, we provide direct evidence showing that TBK1 effectively mediates OC differentiation and function by regulating NF-κB, MAPKs and Akt signals. A TBK1-targeted therapeutic strategy may be useful for the treatment of bone-related disorders.
Subject(s)
NF-kappa B , Osteoclasts , Cell Differentiation , NF-kappa B/metabolism , Osteoclasts/metabolism , Proto-Oncogene Proteins c-akt , Signal TransductionABSTRACT
Artificial tubular molecular pockets bearing polar functionalities on their inner surface are useful model systems for understanding the mechanisms of protein-ligand interactions in living systems. We herein report a pillar[5]arene-derived molecular tube, [P4-(OH)BPO], whose endo conformational isomer endo-[P4-(OH)BPO] possesses an inwardly pointing hydrogen-bond (H-bond) donor (OH) in its deep cavity and a strong H-bond acceptor (CâO) on its predominantly hydrophobic inner surface, rendering it a perfect protein binding pocket mimetic. A fragment-based drug design model was established using endo-[P4-(OH)BPO] and a library of various shape-complementary fragment ligands (1-38). On the basis of the binding affinity data for "fragment-pocket" complexes Gâendo-[P4-(OH)BPO] (G = 1-38), two rationally designed "lead molecules" (39 and 40) were identified as being able to enhance binding affinity significantly by forming H-bonds with both the donor and acceptor of endo-[P4-(OH)BPO]. The described work opens new avenues for developing pillar[n]arene-derived protein binding pocket-mimetic systems for studies of protein-ligand interactions and mechanisms of enzymatic reactions.
Subject(s)
Calixarenes , Hydrogen Bonding , Ligands , Protein BindingABSTRACT
An efficient organocatalytic diastereo- and enantioselective formal [3 + 2] cycloaddition reaction of α-isocyanoacetates with saccharin-derived 1-azadienes catalyzed by a dihydroquinine derived squaramide catalyst has been investigated, and it furnished the corresponding directly linked benzo[d]isothiazole 1,1-dioxide-dihydropyrroles with two adjacent tertiary-quaternary stereocenters in high yields (up to 98%), with moderate to excellent stereoselectivities (up to >20 : 1 dr and 97% ee) under mild conditions.
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Processing of Chinese medicinals with vinegar is one of the characteristic processing techniques. Vinegar is vital for the quality of vinegar-processed decoction pieces. However, there have been no specified standards for adjuvants. Through consulting relevant literature and monographs, we comprehensively reviewed the historical evolution of processing with vinegar in records, selection and application of vinegar, and summarized the relevant standards and current status of vinegar as an adjuvant in China. According to the records in literature, vinegar is effective in activating blood, moving qi, dispersing blood stasis, removing toxin, promoting appetite, and nourishing the liver. Traditionally, rice vinegar is chosen in processing. Nowadays, the vinegar made from rice under solid-state fermentation should be chosen. At present, only food standards can be taken for reference for vinegar in the processing. Integrative and specific inspection indicators are lacking, so the standards for adjuvants need to be improved urgently. In addition, the inadequacy in quality control and management is also a major problem to be solved. Through literature research, we reviewed the historical evolution and research advance in vinegar to provide a reference for the standardization and further research of vinegar used in the Chinese medicinal processing.
Subject(s)
Drugs, Chinese Herbal , Oryza , Acetic Acid , Adjuvants, Pharmaceutic , Quality ControlABSTRACT
To establish the HPLC fingerprint and multi-component determination method of fried Glycyrrhizae Radix et Rhizoma pieces. HPLC analysis was performed on Thermo Acclaim ~(TM)120 C_(18) column(4.6 mm×250 mm, 5 µm). Acetonitrile-0.1% phosphoric acid aqueous solution was taken as the mobile phase for gradient elution. The flow rate was 1 mL·min~(-1),the column temperature was maintained at 30 â, and the detection wavelength was 237 nm and 360 nm. The similarity of 15 batches of fried Glycyrrhizae Radix et Rhizoma pieces was higher than 0.849, and 17 common peaks were identified. Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizic acid were identified; among them, the mass fractions of Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, glycyrrhizic acid were were 0.519%-3.058%, 0.227%-0.389%, 0.070%-0.439%, 0.038%-0.173%, 1.381%-4.252%, respectively. According to the cluster analysis, the 15 batches of decoction pieces were classified into three categories; principal component analysis screened out four principal components, with the cumulative variance contribution rate of 86.630%, indicating that the principal components contained most information of original data. Partial least squares discriminant ana-lysis marked 6 differential components in the decoction pieces. The established fingerprint and multicomponent determination are stable and reliable, and can provide a reference for the quality control of Radix Glycyrrhizae Radix et Rhizomae and fried Glycyrrhizae Radix et Rhizoma pieces.
Subject(s)
Drugs, Chinese Herbal , Chromatography, High Pressure Liquid , Glycyrrhiza , Plant Extracts , Quality ControlABSTRACT
OBJECTIVES: To assess the growth of preterm infants up to a corrected age of 24 months, and to understand the growth trend and pattern of preterm infants. METHODS: A preterm infant follow-up database was established based on the Internet Plus follow-up system. A total of 3 188 preterm infants who were born from April 2018 to April 2021 were enrolled. Their length, weight, and head circumference were recorded at birth and at the corrected ages of 1, 3, 6, 12, 18, and 24 months. The preterm infants were grouped by perinatal factors. The growth curves of these infants were plotted and compared with the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) standard and World Health Organization (WHO) standard. RESULTS: The weight, length, and head circumference curves of each group of preterm infants grouped by various perinatal factors all rose rapidly within the corrected age of 6 months, but the growth rate slowed down after the corrected age of 6 months. Based on the actual age for the groups of preterm infants with different gestational ages (<28 weeks, 28-31+6 weeks, 32-33+6 weeks, and 34-36+6 weeks), the length curve gradually coincided with the WHO curve after the actual age of 9 months (P=0.082), while for the preterm infants with a gestational age of <32 weeks, the weight and head circumference curves were significantly lower than the WHO curves (P<0.001). Based on the corrected age, the physical growth curve of preterm infants with different gestational ages (<28 weeks, 28-31+6 weeks, 32-33+6 weeks, and 34-36+6 weeks) basically coincided with each other (P>0.05). For the infants with extremely low birth weight and the small-for-gestational-age infants, the length, weight, and head circumference curves were significantly lower than those of the INTERGROWTH-21st standard and the WHO standard (P<0.05). CONCLUSIONS: The physical growth rate of preterm infants is faster within the corrected age of 6 months, and the growth rate slows down after the corrected age of 6 months. Preterm infants with a smaller gestational age need longer time to catch up in weight and head circumference. More attention should be paid to the physical growth of extremely preterm infants, extremely low birth weight infants, and small-for-gestational-age infants.
Subject(s)
Infant, Premature , Infant, Small for Gestational Age , Cephalometry , Child, Preschool , Female , Gestational Age , Humans , Infant , Infant, Extremely Low Birth Weight , Infant, Newborn , PregnancyABSTRACT
Visible-light driven photoreactions using metal-organic frameworks (MOFs) as catalysts are promising with regard to their environmental friendly features such as the use of renewable and sustainable energy of visible light and potential catalyst recyclability. To develop potential heterogeneous photocatalysts, a family of three copper(II) coordination polymers bearing different Cu-O assemblies have been synthesized with the ligand 4,4'-disulfo-[1,1'-biphenyl]-2,2'-dicarboxylate acid (H4DSDC), namely, {[Cu7(DSDC)2(OH)6(H2O)10]·xH2O}n (1), {[Cu4(DSDC)(4,4'-bpy)2(OH)4]·2H2O}n (2), and {Cu2(DSDC)(phen)2(H2O)2}n (3) (4,4'-bpy = 4,4'-bipyridine and phen = 1,10-phenanthroline). Complex 1 represents a metal-organic framework featuring a NbO type topology constructed from the infinite linkage of heptanuclear [Cu7(µ3-OH)6(H2O)10]8+ clusters by deprotonated DSDC4- ligands, comprising one-dimensional hexagonal channels of a diameter around 11 Å that are filled with water molecules. The infinite waving {[Cu2(OH)2]2+}n ladderlike chains in complex 2 are bridged by DSDC4- and 4,4'-bpy ligands into a three-dimensional framework. A two-dimensional layered structure is formed in complex 3 due to the existence of terminal phenanthroline ligands. All of the coordination polymers 1-3 are able to catalyze the visible-light driven oxidation of alcohols at mild conditions using hydrogen peroxide as an oxidant, in which complex 1 demonstrates satisfactory efficiency. Significantly for this photoreaction catalyzed by 1, the extent of oxidation over aryl primary alcohols is fully controllable with time-resolved product selectivity, giving either corresponding aldehydes or carboxylate acids in good yields. It is also remarkable that the photocatalyst could be recovered almost quantitatively on completion of the catalytic cycle without any structure change, and could be recycled for catalytic use for at least five cycles with constant efficiency. This photocatalyst with time-resolved selectivity for different products may provide new insight into the design and development of novel catalytic systems.
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A catalytic asymmetric synthesis of 3,4-dihydrocoumarins with adjacent tertiary-quaternary stereocenters by 1,6-addition/transesterification cascade reaction of α-isocyanoacetates with ortho-hydroxyphenyl-substituted para-quinone methides (p-QMs) has been developed. Using a combination of dihydroquinidine-derived aminophosphine and silver nitrate as a binary catalytic system, moderate to good yields, excellent diastereoselectivities (>20 : 1 dr) and good to excellent enantioselectivities (up to 94% ee) were achieved for a wide range of isocyanoacetates and p-QMs.
ABSTRACT
Since Takahashi and Yamanaka reported the generation of induced pluripotent stem cells (iPSCs) in 2006, the field of pluripotent stem cells has entered an unprecedented state of development. It plays an important role in disease modeling, drug discovery and cell therapy, and promotes the development of cell biology and regenerative medicine. At present, iPSC technology has become an important tool for studying of pathological mechanisms. New drugs screened by iPSC technology are being developed, and the number of clinical trials using iPSC-derived cells is gradually increasing. The latest research progress of iPSCs, combined with gene editing technology and 3D organoid methodology, promotes the further applications of iPSCs in disease research. In this review, we introduce the innovation of reprogramming methods in recent years, analyze the advantages and disadvantages of four reprogramming methods: integrated virus vector system, integrated non-viral vector system, non-integrated virus vector system and non-integrated non virus vector system. At the same time, we summarize the latest research progress on iPSCs in disease modeling and clinical treatment strategies, so as to provide a reference for further in-depth research in various fields of iPSCs.