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Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systematically searched to evaluate the preclinical evidence of Tanshinone IIA (Tan IIA) on PF. The quality of the included studies was assessed using a 10-item risk of bias tool, and data were analyzed using RevMan 5.3 software. 22 experiments from 12 studies on a total of 248 animals were included. The results showed that PF phenotype, such as fibrotic score, collagen I (Col-I), collagen III (Col-III), hydroxyproline (Hyp), in the group treated with Tan IIA were significantly lower than those in the model group (p < 0.00001). The potential mechanisms of Tan IIA improvement of PF involve reducing inflammation, antioxidation, and suppressing activation of transforming growth factor beta 1 (TGF-ß1). The subgroup analysis of different models, different rat species, and different dosage time showed significant reduction in fibrotic scores and Hyp levels with Tan IIA. The preclinical evidence indicated that Tan IIA might be a potent and promising agent for PF, but this conclusion should be further confirmed with more research.
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To research the emotional interaction between customers and service staff, single-modal stimuli are being used to activate subjects' emotions while multimodal emotion stimuli with better efficiency are often neglected. This study aims to construct a multimodal emotion stimuli database (CCSIAS) with video records of real work status of 29 service staff and audio clips of interactions between customers and service staff by setting up wide-angle cameras and searching in company's Ocean Engine for 15 consecutive days. First, we developed a tool to assess the emotional statuses of customers and service staff in Study 1. Second, 40 Masters and PhD students were invited to assess the audio and video data to evaluate the emotional states of customers and service staff in Study 2, using the tools developed in Study 1. Third, 118 participants were recruited to test the results from Study 2 to ensure the stability of the derived data. The results showed that 139 sets of stable emotional audio & video data were constructed (26 sets were high, 59 sets were medium and 54 sets were low). The amount of emotional information is important for the effective activation of participants' emotional states, and the degree of emotional activation of video data is significantly higher than that of the audio data. Overall, it was shown that the study of emotional interaction phenomena requires a multimodal dataset. The CCSIAS (https://osf.io/muc86/) can extend the depth and breadth of emotional interaction research and can be applied to different emotional states between customers and service staff activation in the fields of organizational behavior and psychology.
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Achieving single-step syntheses of a set of related compounds divergently and selectively from a common starting material affords substantial efficiency gains when compared with preparing those same compounds by multiple individual syntheses. In order for this approach to be realized, complementary reagent systems must be available; here, a panel of engineered P450BM3 enzymes is shown to fulfill this remit in the selective C-H hydroxylation of cyclobutylamine derivatives at chemically unactivated sites. The oxidations can proceed with high regioselectivity and stereoselectivity, producing valuable bifunctional intermediates for synthesis and applications in fragment-based drug discovery. The process also applies to bicyclo[1.1.1]pentyl (BCP) amine derivatives to achieve the first direct enantioselective functionalization of the bridging methylenes and open a short and efficient route to chiral BCP bioisosteres for medicinal chemistry. The combination of substrate, enzyme, and reaction engineering provides a powerful general platform for small-molecule elaboration and diversification.
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Aminas , Sistema Enzimático del Citocromo P-450 , Hidroxilación , Sistema Enzimático del Citocromo P-450/metabolismo , Oxidación-ReducciónRESUMEN
Introduction: Pulmonary fibrosis (PF) is a fatal chronic lung disease that causes structural damage and decreased lung function and has a poor prognosis. Currently, there is no medicine that can truly cure PF. Vitamin E (VE) is a group of natural antioxidants with anticancer and antimutagenic properties. There have been a few reports about the attenuation of PF by VE in experimental animals, but the molecular mechanisms are not fully understood. Methods: Bleomycin-induced PF (BLM-PF) mouse model, and cultured mouse primary lung fibroblasts and MLE 12 cells were utilized. Pathological examination of lung sections, immunoblotting, immunofluorescent staining, and real-time PCR were conducted in this study. Results: We confirmed that VE significantly delayed the progression of BLM-PF and increased the survival rates of experimental mice with PF. VE suppressed the pathological activation and fibrotic differentiation of lung fibroblasts and epithelial-mesenchymal transition and alleviated the inflammatory response in BLM-induced fibrotic lungs and pulmonary epithelial cells in vitro. Importantly, VE reduced BLM-induced ferritin expression in fibrotic lungs, whereas VE did not exhibit iron chelation properties in fibroblasts or epithelial cells in vitro. Furthermore, VE protected against mitochondrial dysmorphology and normalized mitochondrial protein expression in BLM-PF lungs. Consistently, VE suppressed apoptosis in BLM-PF lungs and pulmonary epithelial cells in vitro. Discussion: Collectively, VE markedly inhibited BLM-induced PF through a complex mechanism, including improving iron metabolism and mitochondrial structure and function, mitigating inflammation, and decreasing the fibrotic functions of fibroblasts and epithelial cells. Therefore, VE presents a highly potential therapeutic against PF due to its multiple protective effects with few side effects.
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PROBLEM: To illustrate the clinical features, treatment strategy, and pregnancy outcome of patients with obstetric antiphospholipid syndrome (OAPS), non-criteria obstetric antiphospholipid syndrome (NC-OAPS) METHOD OF STUDY: A single-center nested case-control study was designed. Patients with a diagnosis of OAPS and NC-OAPS were enrolled. The medical history, coagulation status, and antibody profile data were collected. Patients were given standard anticoagulation therapy with or without glucocorticoids (GC) and/or hydroxychloroquine (HCQ) during pregnancy and were observed for their pregnancy outcome. RESULTS: A total of 47 patients with OAPS and 120 patients with NC-OAPS were finally included, of whom 55 patients met the clinical criteria (subgroup C) and 65 met the laboratory criteria (subgroup L). Pregnancy morbidity showed significant differences: gravida, pregnancy loss in OAPS versus NC-OAPS. The coagulation function was not significantly different between OAPS and NC-OAPS groups, while TT and FIB were significantly higher in the subgroup C. Thromboelastography (TEG) results showed a significantly lower ANGEL in the NC-OAPS group, a higher ANGEL and lower EPL, LY30 in the subgroup L. No differences between groups were observed in treatment strategy. The pregnancy outcomes were not significantly different between NC-OAPS and OAPS groups. CONCLUSIONS: Clinical and laboratory differences were found between OAPS and NC-OAPS groups in this study. Patients in different subgroups of NC-OAPS could be identified with different clinical phenotypes. A relatively hypercoagulable status existed in the OAPS group compared to NC-OAPS, and also in the subgroup L.
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Síndrome Antifosfolípido , Complicaciones del Embarazo , Femenino , Humanos , Embarazo , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Resultado del Embarazo , Anticuerpos Antifosfolípidos , Estudios de Casos y Controles , Complicaciones del Embarazo/diagnósticoRESUMEN
Background: Emotions play a decisive and central role in the workplace, especially in the service-oriented enterprises. Due to the highly participatory and interactive nature of the service process, employees' emotions are usually highly volatile during the service delivery process, which can have a negative impact on business performance. Therefore, it is important to effectively judge the emotional states of customer service staff. Methods: We collected data on real-life work situations of call center employees in a large company. Three consecutive studies were conducted: first, the emotional states of 29 customer service staff were videotaped by wide-angle cameras. In Study 1, we constructed scoring criteria and auxiliary tools of picture-type scales through a free association test. In Study 2, two groups of experts were invited to evaluate the emotional states of customer service staff. In Study 3, based on the results in Study 2 and a multimodal emotional recognition method, a multimodal dataset was constructed to explore how each modality conveys the emotions of customer service staff in workplace. Results: Through the scoring by 2 groups of experts and 1 group of volunteers, we first developed a set of scoring criteria and picture-type scales with the combination of SAM scale for judging the emotional state of customer service staff. Then we constructed 99 (out of 297) sets of stable multimodal emotion datasets. Based on the comparison among the datasets, we found that voice conveys emotional valence in the workplace more significantly, and that facial expressions have more prominant connection with emotional arousal. Conclusion: Theoretically, this study enriches the way in which emotion data is collected and can provide a basis for the subsequent development of multimodal emotional datasets. Practically, it can provide guidance for the effective judgment of employee emotions in the workplace.
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(-)-Galanthamine as a drug for the treatment of Alzheimer's disease has attracted synthetic chemists for decades. However, previous total synthetic and biomimetic approaches often use stoichiometric oxidants (metal oxidants or hypervalent iodine) to prepare the target product. Anodic oxidative coupling offers a sustainable alternative method which is, for the first time, successfully applied to the total synthesis of (-)-galanthamine. We report a new asymmetric total synthesis of (-)-galanthamine by using an anodic aryl-phenol coupling as the key synthetic step.
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Galantamina , Fenol , Biomimética , Oxidantes , FenolesRESUMEN
The processing procedure of traditional Chinese herbal medicines (CHMs) plays an essential role in clinical applications. However, little progress has been made on the quality control of crude and processed products. The present work, taking Radix Scutellariae (RS), wine-processed RS and carbonized RS as a typical case, developed a comprehensive strategy integrating chromatographic analysis and chemometric methods for quality evaluation and discrimination of crude RS and its processed products. Chemical fingerprints were established by high-performance liquid chromatography coupled with photodiode array detector and quadrupole time-of-flight mass spectrometry, and similarity analyses were calculated based on eleven common characteristic peaks. Subsequently, four chemical markers were discovered by back propagation-artificial neural network (BP-ANN) modeling. The selected markers were quantified by the 'single standard to determine multi-components' (SSDMC) method, and then the quantitative data were subjected to principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). Furthermore, support vector machine (SVM) was employed to predict the different processed products of RS. Finally, a hotmap visualization was conducted for clarifying the distribution of major flavonoids among different drugs. Collectively, the proposed strategy might be well-acceptable for quality control of CHMs and their related processed products from the processing mechanism-based perspective.
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Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Espectrometría de Masas/métodos , Scutellaria baicalensis/química , Análisis Discriminante , Flavonoides/química , Análisis de los Mínimos Cuadrados , Análisis de Componente Principal/métodos , Control de Calidad , VinoRESUMEN
Chromatographic fingerprint has been extensively used as a comprehensive approach for quality evaluation of herbal medicines (HMs). However, similar chemical profiles do not always mean similar efficacies. The present work, taking Sophora flower-bud and Sophora flower as a typical case, attempts to develop a rational strategy based on fingerprint-activity relationship modeling to realize quality evaluation from chemical consistency to effective consistency. A total of 57 batches of Sophora samples were collected and their antioxidant and hyaluronidase inhibitory activities were measured. Chemical fingerprints were established by high performance liquid chromatography (HPLC) coupled with photodiode array (PDA) detector and quadrupole time-of-flight mass spectrometry (Q-TOF MS), and similarity analyses were calculated based on eight common characteristic peaks. Subsequently, three principal bioactive markers were discovered by correlating biological effects with chemical fingerprints via partial least squares regression (PLSR) and back propagation-artificial neural network modeling (BP-ANN). The selected markers were quantified by the 'single standard to determine multi-components' method, and then the quantitative data as well as their bioactive properties were subjected to principal component analysis to generate two clear-cut groups. This study not only demonstrates the necessity of effective consistency besides chemical consistency in the quality evaluation of HMs, but also provides an applicable strategy to screen out efficacy-associated markers by fingerprint-activity relationship modeling.
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Flores/química , Extractos Vegetales/química , Sophora/química , Algoritmos , Antioxidantes/química , Compuestos de Bifenilo/química , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Depuradores de Radicales Libres/química , Análisis de los Mínimos Cuadrados , Espectrometría de Masas , Modelos Estadísticos , Modelos Teóricos , Redes Neurales de la Computación , Picratos/química , Plantas Medicinales/química , Análisis de Componente Principal , Control de CalidadRESUMEN
A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3 + 2]-cycloadditive elimination. Cycloadduct 13 was initially elaborated into iodide 27, which, following treatment with Zn, gave aldehyde 28 whose C(9) stereocenter was epimerized. Further elaboration into enoate 38 and Julia-Kocienski olefination with 5 subsequently afforded 39, which was deprotected at C(1) and O(15). Yamaguchi macrolactonization of the seco-acid thereafter afforded a macrocycle that underwent O-desilylation and inversion at C(4) to give (+)-brefeldin A following deprotection.
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A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH2O]nH) in PhMe at 60 °C. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metalation. While N-methylephedrine (NME) is generally the best Zn(OTf)2-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement.