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There are more than 1000 species of microbes reside in the human gut, umberingâ¼1014 microbes. As the invisible organ of human beings, gut microbiota can usually participate in drug metabolism by producing specific enzymes, such as reductase and hydrolytic enzyme, thus affecting the efficacy, toxicity, and bioavailability of drugs. At least 30 commercially available drugs have been shown to be substrates of gut microbes-derived enzymes, and an increasing number of drugs may have the potential to contact with the distal gut with the help of improved release systems or poor solubility/permeability, more drugs are expected to be found to be metabolized through the gut flora. By collecting examples of intestinal flora participating in the metabolism of synthetic drugs and traditional Chinese medicine components, this article provides a comprehensive reference for future researchers to study drug metabolism by intestinal flora. Noticeably, the composition and quantity of intestinal flora varies among individuals, and can be affected by some drug administration (such as antibiotics) or environmental changes (acute plateau hypoxia). This seems to suggest that intestinal flora could have the potential to be a new drug target to affect the efficacy of drugs which can be metabolized by Intestinal flora. Accordingly, understanding the impact of intestinal flora on drug metabolism and clarifying the drug transformation process is of great significance for guiding rational clinical use, individualized use, toxicological evaluation, and promoting drug discovery and development.
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Microbioma Gastrointestinal/fisiologia , Preparações Farmacêuticas/metabolismo , Animais , Medicamentos de Ervas Chinesas/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , FarmacocinéticaRESUMO
BACKGROUND: COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Severe cases developed life-threatening complications, such as respiratory failure, shock, and multiple organs dysfunction. Immunocompromised patients often present atypical presentations of viral infected diseases. CASE PRESENTATION: We report newly diagnosed HIV infections in two patients with COVID-19 in China. In our two cases, both patients with elevated IL-6 received Tocilizumab treatment, but did not present obvious therapeutic effect. CONCLUSIONS: These cases highlight possible co-detection of known immunocompromised diseases such as HIV. The two cases we reported stressed the risk of misdiagnosis, especially during the pandemic of an infectious disease and the importance of extended testing even if in immune-compromised condition the immune state may be ignored.
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Infecções por Coronavirus/complicações , Infecções por HIV/complicações , Pneumonia Viral/complicações , Adulto , Betacoronavirus , COVID-19 , China , Infecções por Coronavirus/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias , Pneumonia Viral/imunologia , SARS-CoV-2RESUMO
OBJECTIVE: To investigate the effects of high-altitude hypoxic environment on the expression of pregnane X receptor (PXR) in rat liver and related mechanism. METHODS: Wistar rats were randomly divided into five groups with 8 rats in each group, the rats were exposed to high-plateau hypoxia for 0 (control group), 12, 24, 36 and 48 h, respectively. Abdominal aortic blood samples were collected for blood gas analysis. HE staining was used to observe the pathological changes of liver tissue. The expression levels of PXR mRNA in liver tissues were determined by RT-PCR. Western blot analysis was performed to determine the protein expression of PXR and protease SUG1 in liver tissues of rats. RESULTS: Compared with the control group, the blood pH of the rats decreased after 12 h of acute hypoxia. After 24 h exposed to hypoxia, SaO2 was lower than 80%, PaO2 was lower than 60 mmHg (1 mmHg=0.133 kPa); and PaCO2 increased after 48 h exposed to hypoxia (P<0.05). There was obvious edema in the central vein of the liver tissue at 12 h and 24 h after exposure to hypoxia. The liver tissue of the rats exposed to hypoxia for 36 h and 48 h showed inflammatory infiltration. The expression of PXR mRNA was significantly decreased by 63%, 96%, 86%, and 85%at 12, 24, 36 h, and 48 h after exposure to hypoxia (all P<0.05), respectively. The protein expression of PXR was significantly up-regulated by 93%and 99%after 36 h and 48 h exposure to hypoxia (all P<0.05), respectively. The protein expression of proteinase SUG1 decreased by 14%, 34%and 46%after 24, 36 and 48 h after hypoxia (all P<0.01). CONCLUSIONS: Acute hypoxia at high altitude can affect the expression of nuclear receptor PXR in rat liver, and protease SUG1 may be a regulatory factor for PXR expression in hypoxia.
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Altitude , Regulação da Expressão Gênica , Hipóxia , Fígado , Receptor de Pregnano X , Animais , Concentração de Íons de Hidrogênio , Hipóxia/complicações , Fígado/fisiologia , Receptor de Pregnano X/genética , Distribuição Aleatória , Ratos , Ratos Wistar , Fatores de TempoRESUMO
As a noble metal with extremely high economic benefits, the recovery of silver ions has attracted a particular deal of attention. However, it is a challenge to recover silver ions efficiently and selectively from aqueous solutions. In this research, the novel metal-organic frameworks (MOFs) adsorbent (Zr-DPHT) is prepared for the highly efficient and selective recovery of silver ions from wastewater. Experimental findings reveal that Zr-DPHT's adsorption of Ag(I) constitutes an endothermic process, with an optimal pH of 5 and exhibits a maximum adsorption capacity of 268.3 mg·g-1. Isotherm studies show that the adsorption of Ag(I) by Zr-DPHT is mainly monolayer chemical adsorption. Kinetic studies indicate that the internal diffusion of Ag(I) in Zr-DPHT may be the rate-limiting step. The mechanism for Ag(I) adsorption on Zr-DPHT involves electrostatic interactions and chelation. In competitive adsorption, Ag(I) has the largest partition coefficient (9.64 mL·mg-1), indicating a strong interaction between Zr-DPHT and Ag(I). It is proven in the adsorption-desorption cycle experiments that Zr-DPHT has good regeneration performance. The research results indicate that Zr-DPHT can serve as a potential adsorbent for efficiently and selectively capturing Ag(I), providing a new direction for MOFs in the recycling field of precious metals.
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Recovering silver from wastewater not only significantly reduces environmental harm but also meets the growing demand for silver in modern industry. Here, a novel metal-organic framework adsorbent (MOF-RD) using rhodanine derivatives as linkers is introduced for the efficient and selective capture of silver ions in real wastewater. The adsorption of MOF-RD followed pseudo-second-order and Sips models, and thermodynamic investigations revealed the process to be endothermic. MOF-RD demonstrated a remarkable adsorption capacity of 707.2 mg·g-1 for Ag(I) at pH 5 and 318 K. The interaction between silver ions and MOF-RD was mainly electrostatic attraction and coordination, with coordination primarily occurring at the CO and CS sites within the rhodanine motif. The practical applicability of MOF-RD for selective adsorption of Ag(I) was validated in actual wastewater with high-concentration competing metal ions. Furthermore, after 10 adsorption-desorption cycle experiments, MOF-RD still retained a strong regenerative capability. The results reveal the good potential of MOF-RD as an adsorbent for selectively recovering Ag(I) from industrial wastewater. Additionally, the strategies and methods adopted in this article also provide new perspectives and technical paths for the separation and recovery of other metal ions in wastewater.
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Objective and Impact Statement: The multi-quantification of the distinct individualized maxillofacial traits, that is, quantifying multiple indices, is vital for diagnosis, decision-making, and prognosis of the maxillofacial surgery. Introduction: While the discrete and demographically disproportionate distributions of the multiple indices restrict the generalization ability of artificial intelligence (AI)-based automatic analysis, this study presents a demographic-parity strategy for AI-based multi-quantification. Methods: In the aesthetic-concerning maxillary alveolar basal bone, which requires quantifying a total of 9 indices from length and width dimensional, this study collected a total of 4,000 cone-beam computed tomography (CBCT) sagittal images, and developed a deep learning model composed of a backbone and multiple regression heads with fully shared parameters to intelligently predict these quantitative metrics. Through auditing of the primary generalization result, the sensitive attribute was identified and the dataset was subdivided to train new submodels. Then, submodels trained from respective subsets were ensembled for final generalization. Results: The primary generalization result showed that the AI model underperformed in quantifying major basal bone indices. The sex factor was proved to be the sensitive attribute. The final model was ensembled by the male and female submodels, which yielded equal performance between genders, low error, high consistency, satisfying correlation coefficient, and highly focused attention. The ensemble model exhibited high similarity to clinicians with minor processing time. Conclusion: This work validates that the demographic parity strategy enables the AI algorithm with greater model generalization ability, even for the highly variable traits, which benefits for the appearance-concerning maxillofacial surgery.
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The recovery of silver ions from wastewater is of great importance due to their adverse environmental impact and significant economic value. This paper introduces a novel adsorbent (CS-AHMT) that can be easily synthesized via a one-step functionalization of chitosan with 4-Amino-3-hydrazino-1,2,4-triazol-5-thiol to efficiently recover silver ions from actual wastewater. CS-AHMT demonstrated superior adsorption performance, achieving an adsorption capacity of 241.4 mg·g-1 at pH 5 and 318 K, and the adsorption equilibrium was rapidly attained within 60 to 120 min. Kinetic and isotherm studies indicate that the adsorption process conforms to the pseudo-nth-order (PNO) and Sips models, suggesting a monolayer adsorption that incorporates both physical and chemical processes, with internal mass transfer being the primary rate-limiting step. Electrostatic and coordination interactions are primarily involved in the adsorption mechanism of silver ions on CS-AHMT, as further validated by density functional theory (DFT) calculations. The selectivity and practical applicability of CS-AHMT were confirmed in real wastewater containing high concentrations of competing ions. The findings underscore the potential of CS-AHMT as an effective adsorbent for silver ion recovery in wastewater treatment applications.
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As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
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COVID-19 , Humanos , Medicina Tradicional Chinesa , SARS-CoV-2 , Estado Terminal , Resultado do TratamentoRESUMO
BACKGROUND: Immediate implant placement in the esthetic area requires comprehensive assessments with nearly 30 quantitative indexes. Most artificial intelligence (AI)-driven measurements of quantitative indexes depend on segmentation or landmark detection, which require extra labeling of images and contain possible intraclass errors. METHODS: For the initial attempt, the method was tested on sagittal root inclination measurement. This study had developed an accurate and efficient end-to-end model incorporating a convolutional neural network (CNN) based on unlabeled cone-beam computed tomography (CBCT) images for immediate implant placement diagnosis and treatment. The model took pretrained ResNeXt101 as the backbone and was constructed based on 2,920 CBCT images with corresponding angles of the tooth axis and bone axis. The performance of our CNN model was evaluated on a separate test set. RESULTS: Our model exhibited high prediction accuracy in sagittal root inclination measurements, as evidenced by the low mean average error of 2.16°, the high correlation coefficient of 0.915 to manual measurement, and the narrow 95% confidence interval shown by Bland-Altman plots. The intraclass correlation coefficient further confirmed the measurement accuracy of our model was comparable with that of junior clinicians. The model took merely 0.001 seconds for each CBCT image, making it highly efficient. To better understand the model's quality, we visualized our end-to-end CNN model through Guided Backpropagation, Grad-CAM, and Guided Grad-CAM, and confirmed its effectiveness in region recognition. CONCLUSIONS: We succeeded in taking the first step in constructing the end-to-end immediate implant placement AI tool through sagittal root inclination measurements without intermediate steps and extra labeling on images.
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Inteligência Artificial , Estética Dentária , Tomografia Computadorizada de Feixe Cônico/métodos , Redes Neurais de Computação , Raiz Dentária/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodosRESUMO
This study is to screen 23 blank O/W type microemulsion (ME) samples, that is 15 samples from our laboratory, and 8 samples from literature; compare the conductivity-water content curve (CWCC) method and visual method in determining the critical water content during O/W type MEs' formation, to analyze the deficiency and the feasibility of visual method and to exploxe scientific meanings of CWCC method in judging the critical water content of O/W type MEs during formation. The results show that there is a significant difference between the theoretical feasible CWCC method and visual method in determining the critical water content (P<0.001), and the results judged by conductivity is higher than that by eye-based water content. Therefore, this article firmly confirmed the shortcomings of visual method and suggested that the eye-base "critical water content" may falls into continuous ME stage during O/W MEs' formation. Further more, the CWCC method has theoretical feasibility and scientific meanings in determining the critical water content of O/W type MEs during formation.