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Meiosis is essential for gamete production in all sexually reproducing organisms. It entails two successive cell divisions without DNA replication, producing haploid cells from diploid ones. This process involves complex morphological and molecular differentiation that varies across species and between sexes. Specialized genomic events like meiotic recombination and chromosome segregation are tightly regulated, including preparation for post-meiotic development. Research in model organisms, notably yeast, has shed light on the genetic and molecular aspects of meiosis and its regulation. Although mammalian meiosis research faces challenges, particularly in replicating gametogenesis in vitro, advances in genetic and genomic technologies are providing mechanistic insights. Here we review the genetics and molecular biology of meiotic gene expression control, focusing on mammals.
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Meiose , Saccharomyces cerevisiae , Animais , Meiose/genética , Saccharomyces cerevisiae/genética , Gametogênese/genética , Segregação de Cromossomos/genética , Replicação do DNA , MamíferosRESUMO
A conceptual shift toward next-generation wearable electronics is driving research into self-powered electronics technologies that can be independently operated without plugging into the grid for external power feeding. Triboelectric nanogenerators (TENGs) are emerging as a key component of self-powered electronics, but a power type mismatch between supply and demand limits their direct implementation into wearable self-powered electronics. Here, a TENG with switchable power mode capability is reported where the charge flow direction is modulated over the course of slow and random mechanical stimuli, with exceptional rectification capabilities as high as ≈133, stable outputs over the cycles, and design flexibility in different platforms. Importantly, the remarkable switchable power generation with fabric counter materials illuminates a new path for the smooth integration of flexible TENGs into wearable self-powered electronics.
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Short-chain fatty acids (SCFAs) are the primary energy source of colonic epithelial cells, but oral SCFAs are digested, absorbed, or degraded before reaching the colon. The acylated starch with SCFAs can be fermented and release specific SCFAs under the action of colonic intestinal microbiota. This review first introduces the preparation method, reaction mechanism, and substitution factors. Second, the structure, physical and chemical properties, in vitro function, and mechanism of acylated starch were expounded. Finally, the application of acylated starch in foods is introduced, and its safety is evaluated, providing a basis for the further development of acylated starch-based foods. The acylated starch obtained by different acylation types and preparation methods is different in particle, molecular, and crystal structures, leading to changes in the function and physicochemical properties. Meanwhile, acylated starch has the functional potential of targeted delivery of SCFAs to the colon, which can increase SCFAs in feces and intestine, selectively regulate the intestinal microbiota, and produce a prebiotic effect conducive to host health. The safety of acetylated starch has been supported by relevant studies, which have been widely used in various food fields and have great potential in the food industry.
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BACKGROUND: To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. METHOD: The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. RESULTS: At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665-7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324-3.631) and the long term (OR = 1.926, 95%CI 1.021-3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250-3.166), slowness (OR = 1.395, 95%CI 1.044-1.865), and exhaustion (OR = 2.827, 95%CI 2.150-3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004-4.109) onset during the long-term. CONCLUSION: Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.
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Depressão , Fragilidade , Humanos , Estudos Longitudinais , Masculino , Feminino , Depressão/epidemiologia , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Fragilidade/epidemiologia , Fragilidade/psicologia , Estudos Transversais , Prevalência , Idoso Fragilizado/estatística & dados numéricos , Idoso Fragilizado/psicologia , Idoso de 80 Anos ou mais , Inquéritos e QuestionáriosRESUMO
Understanding the developmental characteristics of microbial communities in biofilms is crucial for designing targeted functional microbial enhancements for the remediation of complex contamination scenarios. The strong prioritization effect of microorganisms confers the ability to colonize strains that arrive first dominantly. In this study, the auto-aggregating denitrifying bacterial Pseudomonas stutzeri strain YC-34, which has both nitrogen and chromium removal characteristics, was used as a biological material to form a stable biofilm system based on the principle of dominant colonization and biofortification. The effect of the biofilm system on nitrogen and chromium removal was characterized by measuring the changes in the quality of influent and effluent water. The pattern of biofilm changes was analyzed by measuring biofilm content and thickness and characterizing extracellular polymer substances (EPS). Further analysis of the biofilm microbiota characteristics and potential functions revealed the mechanism of strain YC-34 biofortified biofilm. The results revealed that the biofilm system formed could achieve 90.56% nitrate-nitrogen removal with an average initial nitrate-nitrogen concentration of 51.9â¯mg/L and 40% chromium removal with an average initial hexavalent chromium Cr(VI) concentration of 7.12â¯mg/L. The biofilm properties of the system were comparatively analyzed during the biofilm formation period, the fluctuation period of Cr(VI)-stressed water quality, and the stabilization period of Cr(VI)-stressed water quality. The biofilm system may be able to increase the structure of hydrogen bonds, the type of protein secondary structure, and the abundance of amino acid-like components in the EPS, which may confer biofilm tolerance to Cr(VI) stress and allow the system to maintain a stable biofilm structure. Furthermore, microbial characterization indicated an increase in microbial diversity in the face of chromium stress, with an increase in the abundance of nitrogen removal-associated functional microbiota and an increasing trend in the abundance of nitrogen transfer pathways. These results demonstrate that the biofilm system is stable in nitrogen and chromium removal. This bioaugmentation method may provide a new way for the remediation of heavy metal-polluted water bodies and also provides theoretical and application parameters for the popularization and application of biofilm systems.
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Desnitrificação , Nitratos , Nitratos/metabolismo , Nitrogênio/metabolismo , Cromo/metabolismo , Biofilmes , Bactérias/metabolismoRESUMO
BACKGROUND: Nurses play an important role in healthcare development. The increasing demands for nurses mean that nursing schools at the undergraduate level have the responsibility to ensure patient safety and quality care through a well-designed curriculum. This research aimed to evaluate the effect of the teaching method combined with situational awareness and case-based seminars in a comprehensive nursing skills practice course on the level of self-directed learning, professional identity, academic self-efficacy, theoretical scores, practical scores, teaching satisfaction, and student competence among nursing students. METHODS: The research population comprised was of the grades of 2019 and 2020 at Wannan Medical College in Anhui Province, China (n = 169, response rate 77.88%). The observation group from grade 2020 used the teaching method combined with situational awareness and case-based seminars, whereas the control group from grade 2019 used the traditional teaching mode. General information, self-directed learning, a professional identity, and academic self-efficacy were compared between the two groups. This research used means and standard deviations, chi-square, the Shapiro-Wilk test, and an independent sample t-test for statistical analyses. RESULTS: Compared with the control group, the total scores for self-directed learning, professional identity, and academic self-efficacy were higher in the observation group (78.80 ± 7.89 vs 60.21 ± 7.44, 63.39 ± 7.87 vs 52.35 ± 7.68, and 22.31 ± 3.30 vs 21.28 ± 2.31, respectively, with P < 0.05 for all scores). More significant improvements were made in the observation group on the level of theoretical scores (81.39 ± 3.32 vs 76.28 ± 5.90) and practical scores (93.32 ± 4.70 vs 90.67 ± 5.09) (P < 0.05). Meanwhile, teaching satisfaction, which includes teaching method (66/18 vs 32/53) and teacher-student interaction (72/12 vs 34/51), and student competence, which includes team cooperation (67/17 vs 39/46), critical thinking (60/24 vs 31/54), and communication skills (67/17 vs 38/47) after the intervention (P < 0.05). There was no significant difference in social persuasion (P > 0.05). CONCLUSION: The teaching method combined with situational awareness and case-based seminars in a comprehensive nursing skills practice course has the potential to improve the level of self-directed learning, professional identity, and academic self-efficacy, and it increases theoretical scores, practical scores, teaching satisfaction, and student competence.
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Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Conscientização , Bacharelado em Enfermagem/métodos , Aprendizagem , CurrículoRESUMO
Bound states in the continuum (BICs) with infinite quality factor (Q-factor) and significant field enhancement pave the way for realizing highly sensitive optical sensors with enhanced light-matter interactions on the nanoscale. However, current optical sensing methods are difficult to discriminate between isotropic and anisotropic media from resonance spectral lines, resulting in optical sensing methods still being limited to isotropic media. In this work, we demonstrate that BICs can be realized by modulating the period of structural units to convert BICs to QBICs without changing their space group symmetry, and propose a polarization-independent metasurfaces-based realization of highly sensitive refractive index sensors for isotropic and anisotropic media as well as discrimination. We propose a metasurface of tetrameric silicon nanoboxes with C4 symmetry as structural units to achieve the conversion of BICs to QBICs by modulating the period of structural units without changing the geometry of the structure. Two QBICs modes dominated by electric toroidal dipole and magnetic toroidal dipole are identified by multipolar decomposition and electromagnetic distribution calculations. Meanwhile, we realize the refractive index detection and resolution of isotropic and anisotropic media based on polarization-independent metasurfaces combined with isotropic and anisotropic media layers. Our work provides what we believe to be a new method for realizing the fast resolution and refractive index optical sensing of isotropic and anisotropic media, and offers new ideas for the design and application of polarization-independent metasurfaces.
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Aniridia is a panocular condition characterized by impaired eye development and vision, which is mainly due to the haploinsufficiency of the paired-box-6 (PAX6) gene. Like what is seen in aniridia patients, Pax6-deficient mice Pax6Sey-Neu/+ exhibit a varied degree of ocular damage and impaired vision. Our previous studies showed that these phenotypes were partially rescued by PD0325901, a mitogen-activated protein kinase kinase (MEK or MAP2K) inhibitor. In this study, we assessed the long-term efficacy of PD0325901 treatment in retinal health and visual behavior. At about one year after the postnatal treatment with PD0325901, Pax6Sey-Neu/+ mice showed robust improvements in retina size and visual acuity, and the elevated intraocular pressure (IOP) was also alleviated, compared to age-matched mice treated with vehicles only. Moreover, the Pax6Sey-Neu/+ eyes showed disorganized retinal ganglion cell (RGC) axon bundles and retinal layers, which we termed as hotspots. We found that the PD treatment reduced the number and size of hotspots in the Pax6Sey-Neu/+ retinas. Taken together, our results suggest that PD0325901 may serve as an efficacious intervention in protecting retina and visual function in aniridia-afflicted subjects.
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Aniridia , Fatores de Transcrição Box Pareados , Animais , Aniridia/genética , Modelos Animais de Doenças , Proteínas do Olho/genética , Haploinsuficiência , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Fator de Transcrição PAX6/genética , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , RetinaRESUMO
The destruction of alveolar bone is a crucial manifestation of severe chronic periodontitis, which stem cell-based bioengineered therapies are expected to cure. Therefore, a cost-effective, reproducible, quantifiability and easier to administrate animal model that mimics human periodontitis is of great importance for further endeavor. In this study, we created periodontitis rat models in silk ligation group, bone defect group and bone defect/silk ligation group, respectively. Obvious periodontal inflammation but slight alveolar bone resorption was observed in the ligation group, while surgical trauma was not robust enough to continually worsen the constructed bone defect area in the bone defect group. In the bone defect/ligature group, significant and stable periodontal inflammation was the most enduring with similar evolving pathological patterns of human periodontitis. It also exhibited enhanced clinical similarity and confirmed its superiority in quantitativeness. The present rat model is the first study to reproduce a pathological process similar to human periodontitis with reliable stability and repeatability, manifesting a priority to previous methods. Day 9-12 is the best time for reproducing severe periodontitis syndromes with vertical bone resorption in this model.
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Perda do Osso Alveolar , Modelos Animais de Doenças , Periodontite , Ratos , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/patologia , Animais , Humanos , Ligadura , Periodontite/complicações , Periodontite/patologia , SedaRESUMO
A novel, low-cost and effective in-needle solid-phase microextraction device was developed for the enrichment of trace polycyclic aromatic hydrocarbons in water samples. The in-needle solid-phase microextraction device could be easily assembled by inserting hydrofluoric acid-etched wires, which were used as adsorbent, into a 22-gauge needle tube within spring supporters. Compared with the commercial solid-phase microextraction fiber, the developed device has higher efficiency for the extraction of polycyclic aromatic hydrocarbons with four to six rings from water samples using the optimized extraction conditions. With gas chromatography equipped with a flame ionization detector, the limits of detection for the polycyclic aromatic hydrocarbons with four to six rings ranged from 0.0020 to 0.0067 ng/mL. The relative standard deviations for one needle and needle-to-needle extractions were in the range of 5.2-9.9% (n = 5) and 3.4-12.3% (n = 5), respectively. The spiked recoveries of the polycyclic aromatic hydrocarbons in tap water samples ranged from 73.2 to 95.4%. This in-needle solid-phase microextraction device could be a good field sampler because of the low sample loss over a long storage time.
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An ideal gene carrier requires an excellent gating system to efficiently load, protect, deliver, and release environmentally sensitive nucleic acids on demand. Presented in this communication is a polymersome with a "boarding gate" and a "debarkation gate" in the membrane to complete the above important missions. This dually gated polymersome is self-assembled from a block copolymer, poly(ethylene oxide)- block-poly[ N-isopropylacrylamide- stat-7-(2-methacryloyloxyethoxy)-4-methylcoumarin- stat-2-(diethylamino)ethyl methacrylate] [PEO- b-P(NIPAM- stat-CMA- stat-DEA)]. The hydrophilic PEO chains form the coronas of the polymersome, whereas the temperature and pH-sensitive P(NIPAM- stat-CMA- stat-DEA) block forms the dually gated heterogeneous membrane. The temperature-controlled "boarding gate" can be opened at room temperature for facile encapsulation of siRNA and plasmid DNA into polymersomes directly in aqueous solution. The "debarkation gate" can be triggered by proton sponge effect for intracellular release. Biological studies confirmed the successful encapsulation of siRNA and plasmid DNA, efficient in vitro and in vivo gene transfection, and the expression of green fluorescent protein (GFP) from GFP-encoding plasmid, suggesting that this kind of polymersome with a dual gating system can serve as an excellent biomacromolecular shuttle for gene delivery and other biological applications.
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Acrilamidas/química , DNA/administração & dosagem , Técnicas de Transferência de Genes , Metacrilatos/química , Plasmídeos/administração & dosagem , Polietilenoglicóis/química , RNA Interferente Pequeno/administração & dosagem , Animais , Linhagem Celular , Cumarínicos/química , DNA/genética , Proteínas de Fluorescência Verde/genética , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos Nus , Plasmídeos/genética , RNA Interferente Pequeno/genética , Temperatura , Transfecção/métodosRESUMO
The human Y-chromosome has proven to be a powerful tool for tracing the paternal history of human populations and genealogical ancestors. The human Y-chromosome haplogroup Q is the most frequent haplogroup in the Americas. Previous studies have traced the origin of haplogroup Q to the region around Central Asia and Southern Siberia. Although the diversity of haplogroup Q in the Americas has been studied in detail, investigations on the diffusion of haplogroup Q in Eurasia and Africa are still limited. In this study, we collected 39 samples from China and Russia, investigated 432 samples from previous studies of haplogroup Q, and analyzed the single nucleotide polymorphism (SNP) subclades Q1a1a1-M120, Q1a2a1-L54, Q1a1b-M25, Q1a2-M346, Q1a2a1a2-L804, Q1a2b2-F1161, Q1b1a-M378, and Q1b1a1-L245. Through NETWORK and BATWING analyses, we found that the subclades of haplogroup Q continued to disperse from Central Asia and Southern Siberia during the past 10,000 years. Apart from its migration through the Beringia to the Americas, haplogroup Q also moved from Asia to the south and to the west during the Neolithic period, and subsequently to the whole of Eurasia and part of Africa.
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Cromossomos Humanos Y/genética , Genética Populacional , Haplótipos/genética , Migração Humana , Ásia , China , Humanos , Repetições de Microssatélites/genética , Filogenia , Polimorfismo de Nucleotídeo Único , SibériaRESUMO
Antimicrobial peptides (AMPs) have been attracting much attention due to their excellent antimicrobial efficiency and low rate in driving antimicrobial resistance (AMR), which has been increasing globally to alarming levels. Conjugation of AMPs into functional polymers not only preserves excellent antimicrobial activities but reduces the toxicity and offers more functionalities, which brings new insight toward developing multifunctional biomedical materials such as hydrogels, polymer vesicles, polymer micelles, and so forth. These nanomaterials have been exhibiting excellent antimicrobial activity against a broad spectrum of bacteria including multidrug-resistant (MDR) ones, high selectivity, and low cytotoxicity, suggesting promising potentials in wound dressing, implant coating, antibiofilm, tissue engineering, and so forth. This Perspective seeks to highlight the state-of-the-art strategy for the synthesis, self-assembly, and biomedical applications of AMP-polymer conjugates and explore the promising directions for future research ranging from synthetic strategies, multistage and stimuli-responsive antibacterial activities, antifungi applications, and potentials in elimination of inflammation during medical treatment. It also will provide perspectives on how to stem the remaining challenges and unresolved problems in combating bacteria, including MDR ones.
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Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Nanoestruturas/química , Polímeros/química , Anti-Infecciosos/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bandagens , Resistência Microbiana a Medicamentos , Humanos , Micelas , Testes de Sensibilidade Microbiana , Polimerização , Polímeros/síntese química , Próteses e Implantes , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos , CicatrizaçãoRESUMO
Natural extracellular matrices (ECMs) have been widely used as a support for the adhesion, migration, differentiation, and proliferation of adipose-derived stem cells (ADSCs). However, poor mechanical behavior and unpredictable biodegradation properties of natural ECMs considerably limit their potential for bioapplications and raise the need for different, synthetic scaffolds. Hydrogels are regarded as the most promising alternative materials as a consequence of their excellent swelling properties and their resemblance to soft tissues. A variety of strategies have been applied to create synthetic biomimetic hydrogels, and their biophysical and biochemical properties have been modulated to be suitable for cell differentiation. In this review, we first give an overview of common methods for hydrogel preparation with a focus on those strategies that provide potential advantages for ADSC encapsulation, before summarizing the physical properties of hydrogel scaffolds that can act as biological cues. Finally, the challenges in the preparation and application of hydrogels with ADSCs are explored and the perspectives are proposed for the next generation of scaffolds.
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Tecido Adiposo/citologia , Diferenciação Celular , Hidrogéis/farmacologia , Células-Tronco/citologia , Tecido Adiposo/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Humanos , Hidrogéis/síntese química , Hidrogéis/química , Hidrogéis/metabolismo , Células-Tronco/efeitos dos fármacosRESUMO
Antimicrobial resistance is an increasingly problematic issue in the world and there is a present and urgent need to develop new antimicrobial therapies without drug resistance. Antibacterial polymers are less susceptible to drug resistance but they are prone to inducing serious side effects due to high positive charge. Herein we report a peptide-grafted hyperbranched polymer which can self-assemble into unusual nanosheets with highly effective intrinsically antibacterial activity but weak positive charges (+ 6.1 mV). The hyperbranched polymer was synthesized by sequential Michael addition-based thiol-ene and free radical mediated thiol-ene reactions, and followed by ring-opening polymerization of N-carboxyanhydrides (NCAs). The nanosheet structure was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) studies. Furthermore, a novel "wrapping and penetrating" antibacterial mechanism of the nanosheets was revealed by TEM and it is the key to significantly decrease the positive charges but have a very low minimum inhibitory concentration (MIC) of 16 µg mL(-1) against typical Gram-positive and Gram-negative bacteria. Overall, our synthetic strategy demonstrates a new insight for synthesizing antibacterial nanomaterials with weak positive charges. Moreover, the unique antibacterial mechanism of our nanosheets may be extended for designing next-generation antibacterial agents without drug resistance.
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Antibacterianos/síntese química , Nanoestruturas/química , Peptídeos/química , Polímeros/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Sobrevivência Celular , Células Cultivadas , Capacitância Elétrica , Eritrócitos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Polímeros/química , Polímeros/farmacologia , Polímeros/toxicidade , Propriedades de SuperfícieRESUMO
Lobaplatin, consisting of two diastereoisomers, is a third-generation platinum antineoplastic agent that has shown encouraging anticancer activity in a variety of tumor types. To investigate any stereospecificity in the pharmacokinetics of lobaplatin, a novel, simple, rapid and sensitive supercritical fluid chromatography with tandem mass spectrometry method was developed for the simultaneous quantitation of lobaplatin diastereoisomers in rat plasma. After a simple protein precipitation with methanol, the analytes and dexpantoprazole (internal standard) were chromatographed on an Acquity UPC(2) system with a Chiralcel OZ-RH column using a mobile phase consisting of carbon dioxide and methanol (65:35, v/v) at 40°C over 6 min. The assay was linear over a concentration range of 25-15,000 ng/mL for both diastereoisomers using 100 µL of rat plasma for sample preparation. The lower limit of quantification was 25 ng/mL for both compounds, which was sufficient to detect the diastereoisomers in the incurred samples within this study. Intra- and inter-day precisions were below 11.8% and the accuracies were below 4.5%. The validated method was successfully applied to a pharmacokinetic study after an intravenous administration of 7.6 mg/kg lobaplatin to rats. There was no apparent stereospecificity in the pharmacokinetics between the two diastereoisomers of lobaplatin.
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Cromatografia com Fluido Supercrítico/métodos , Ciclobutanos/sangue , Compostos Organoplatínicos/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Área Sob a Curva , Ciclobutanos/farmacocinética , Meia-Vida , Limite de Detecção , Compostos Organoplatínicos/farmacocinética , Ratos , Reprodutibilidade dos Testes , EstereoisomerismoRESUMO
2-phenylethanol (2-PE), an aromatic alcohol with a rose fragrance, is the second most widely used flavoring substance in the world. It is widely used in the cosmetic, food, and pharmaceutical industries. This paper introduces the chemical synthesis methods of 2-PE and the synthetic pathways in plants and microorganisms, summarizes the strategies to improve the microbial synthesis of 2-PE, reviews the research progress in de novo synthesis of 2-PE in microorganisms, and makes an outlook on the research prospects, aiming to provide a theoretical basis for the industrial production of 2-PE.
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Álcool Feniletílico , Álcool Feniletílico/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/síntese química , Microbiologia Industrial , Aromatizantes/síntese química , Aromatizantes/metabolismo , Bactérias/metabolismo , Plantas/metabolismoRESUMO
Primordial germ cells (PGCs) are the founder cells of the germline. The ability to generate PGC-like cells (PGCLCs) from pluripotent stem cells has advanced our knowledge of gametogenesis and holds promise for developing infertility treatments. However, generating an ample supply of PGCLCs for demanding applications such as high-throughput genetic screens has been a limitation. Here, we demonstrated that simultaneous overexpressing 4 transcriptional factors - Nanog and three PGC master regulators Prdm1, Prdm14 and Tfap2c - in suspended mouse epiblast like cells (EpiLCs) and formative embryonic stem cells (ESCs) results in efficient and cost-effective production of PGCLCs. The overexpression of Nanog enhances the PGC regulatory network and suppresses differentiation of somatic lineages, enabling a significant improvement in the efficiency of PGCLC production. Transcriptomic analysis reveals that differentiated PGCLCs exhibit similarities to in vivo PGCs and are more advanced compared to cytokine-induced PGCLCs. These differentiated PGCLCs could be sustained over prolonged periods of culture and could differentiate into spermatogonia-like cells in vitro. Importantly, the ability to produce PGCLCs at scale, without using costly cytokines, enables biochemical and functional genomic screens to dissect mechanisms of germ cell development and infertility.