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BACKGROUND: Oral Mucositis (OM) is a common and highly symptomatic complication of cancer therapy that affects patient function and quality of life. Jingzhi Niuhuangjiedu Tablet (JNT) is derived from the famous Chinese herbal formulas Huanglian Jiedu and Fangfeng Tongsheng decoctions, which have been widely used to treat heat toxin syndrome diseases, such as acute pharyngitis, periodontitis, oral ulcers, and oral mucositis (OM), but the underlying mechanism remains unclear. OBJECTIVES: This study validated the efficacy and explored the potential mechanisms of JNT in the treatment of OM by integrating network pharmacological analyses and experimental verification. METHODS: Network pharmacology and molecular docking techniques were used to predict the active components, key targets, and potential mechanisms of action of JNT against OM. The rat OM model was established by administering 5-Fluorouracil (5-FU) and acetic acid to the rat oral mucosa. Lipopolysaccharide (LPS)-treated human gingival fibroblasts (HGFs) were used as an inflammatory cell model. The GFP-NFκB HEK293T cell line was transfected to evaluate the anti-NFκB activity of JNT. RESULTS: A total of 236 Chinese herbal components and 201 corresponding targets were predicted for OM treatment using JNT. Bicuculine, luteolin, wogonin, and naringenin were identified as the important active compounds, while AKT1, ALB, IL6, MAPK3, and VEGFA were considered to be the major targets. Molecular docking revealed that these active compounds exhibited strong binding interactions with their targets. In vivo and in vitro experiments demonstrated that the anti-OM effect of JNT might be closely related to AKT1, NFκB, caspase-1, and NLRP3, as well as biological processes, such as inflammatory response and oxidative stress. CONCLUSION: Network pharmacological and experimental evidence indicates that JNT has a potential therapeutic effect on OM by regulating the Akt/NFκB/NLRP3 pathway.
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The performance of lithium metal batteries can be significantly enhanced by incorporating fluorinated ether-based electrolytes, yet the solid electrolyte interphase (SEI) formation mechanism on lithium metal surfaces remains elusive. This study employs classical and ab initio molecular dynamics simulations to investigate the decomposition mechanisms of lithium bis(fluoromethanesulfonyl)imide (LiFSI) in 1,2-diethoxyethane (DEE) and its fluorinated analogues, F5DEE and F2DEE, when in contact with lithium metal. Our findings indicate that F5DEE-based electrolytes favor the formation of a FSI-rich primary solvation shell around Li+, while F2DEE-based electrolytes yield a solvent-rich environment. The normalized number density at the Li/electrolyte/Li interface shows a depletion of FSI anions in the electrochemical double layer (EDL) structure near the Li anode upon charging, with the distance between the first main peak of the FSI anion and Li anode following the order F5DEE < DEE < F2DEE. Analysis of the electronic projected density of states and charge transfer dynamics unveils the reductive dissociation pathways of FSI anions and fluorinated DEE solvents on the lithium metal surface, taking into account the influence of the EDL structure. DEE is identified as the most reduction-stable solvent, leading to the selective dissociation of FSI anions and the formation of an entirely inorganic SEI. In contrast, F2DEE displays a pronounced reduction tendency, forming an organic-rich SEI due to the solvent-dominated lowest unoccupied molecular orbital at the interface. F5DEE, competing with FSI anions for reduction, results in the formation of an inorganic-rich hybrid SEI with the highest LiF content. The simulation results correlate well with experimental observations and underscore the pivotal role of various fluorinated functional groups in the formation of EDL and SEI near the lithium metal surface.
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INTRODUCTION: Antithrombin (AT) deficiency is a rare but highly thrombogenic inherited thrombophilia. Its association with adverse pregnancy outcomes (APO) is undefined. There is limited guidance on managing AT deficiency in pregnancy. Some significant issues remain controversial, including risk assessment for prophylactic anticoagulation, anticoagulant therapy, and monitoring. Our goal was to examine if the antepartum management of patients with AT deficiency affected their pregnancy outcomes. MATERIALS AND METHODS: This retrospective, single-center observational study included pregnant women with inherited AT deficiency in Peking Union Medical College Hospital between 2013 and 2024. RESULTS: Seventeen pregnancies in 6 women with AT deficiency were identified. A total of 7 pregnancies received adjusted-dose low-molecular-weight heparin (LMWH) and were monitored by anti-Xa level, AT activity, and D-dimer. There were 5 live births (all received LMWH), 7 second-trimester abortions (1 received LMWH), and 5 early pregnancy losses (1 received LMWH). There were 5 abruptio placentae events (3 received LMWH) and 7 thrombotic events (2 received LMWH). CONCLUSIONS: AT deficiency is at least an important partial factor contributing to APO. It is suggested to make a full assessment of AT patients both for venous thrombus embolism and APO risk. We observed a high prevalence of heparin resistance and a positive correlation between adequate anticoagulation and pregnancy outcome based on tight monitoring with anti-Xa level and timely adjustment of the LMWH dosage.
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This study aimed to define the role of heterogeneity of liver parenchymal enhancement on computed tomography (CT) in the survival of patients with hepatocellular carcinoma (HCC) after hepatic resection. The medical records of patients with HCCs and who had undergone hepatic resection were retrospectively reviewed. The standard deviation (SD) of three different enhanced CT scan images was used to estimate the heterogeneity of liver parenchymal enhancement: SD of > 5.6, heterogenous enhancement, and SD of ≤ 5.6, homogeneous enhancement. A total of 57 patients had heterogenous enhancement, and 143 patients had homogeneous enhancement. The patients with heterogenous enhancement had longer disease-free and overall survivals than those with other enhancements (log-rank test, P < 0.001 and P = 0.036). The pathologic exam showed that heterogenous enhancement tended to develop septa in the peritumoral liver tissues. The prevalence of CD8+ cells was significantly higher in the peritumor liver tissues with septa than in those without (0.83% vs. 0.26%, P < 0.001). The peritumoral CD8/Foxp3 ratio was higher in the liver tissues with septa than in those without (1.22 vs. 0.47, P = 0.001), and patients with CD8/Foxp3 of > 0.8 had better overall survival than those with CD8/Foxp3 of ≤ 0.8 (log-rank test, P = 0.028). In conclusion, patients who had undergone hepatic resection with a heterogenous liver parenchymal enhancement tended to develop hepatic septa, which was associated with a higher CD8/Foxp3 ratio and longer survival. Therefore, contrast-enhanced CT scans might be a useful tool to predict the outcome of HCC.
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The environmental stability of infectious viruses in the laboratory setting is crucial to the transmission potential of human respiratory viruses. Different experimental techniques or conditions used in studies over the past decades have led to diverse understandings and predictions for the stability of viral infectivity in the atmospheric environment. In this paper, we review the current knowledge on the effect of simulated atmospheric conditions on the infectivity of respiratory viruses, mainly focusing on influenza viruses and coronaviruses, including severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. First, we summarize the impact of the experimental conditions on viral stability; these involve the methods of viral aerosol generation, storage during aging and collection, the virus types and strains, the suspension matrixes, the initial inoculum volumes and concentrations, and the drying process. Second, we summarize and discuss the detection methods of viral infectivity and their disadvantages. Finally, we integrate the results from the reviewed studies to obtain an overall understanding of the effects of atmospheric environmental conditions on the decay of infectious viruses, especially aerosolized viruses. Overall, this review highlights the knowledge gaps in predicting the ability of viruses to maintain infectivity during airborne transmission.
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With the wave of positive psychology in second language acquisition, more emotion factors are gaining scholarly attention. Despite extensive research on Trait Emotional Intelligence (TEI), burnout and boredom in English as a Foreign Language (EFL) studies, the interplay of these variables remains unknown and the related impact on EFL learner's English Language Performance (ELP) is still underexplored. Given this, in light of Control-Value Theory (CVT), the present study used a quantitative method to examine the mediating roles of boredom and burnout in the connection between TEI and ELP among Chinese university students engaged in EFL endeavor. Data were collected from 489 second-year EFL students. Structural equation modeling was utilized to analyze the relationships. Results revealed that TEI significantly influences ELP among Chinese EFL university students, through its correlation with both boredom and burnout. Higher levels of TEI are associated with reduced experiences of these negative states, which in turn are linked to improved language performance. These may imply that teacher educators should integrate emotional intelligence training into curricula and professional development to improve students' effectiveness and learning outcome.
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Tedio , Inteligencia Emocional , Estudiantes , Humanos , Masculino , Estudiantes/psicología , Femenino , Adulto Joven , Inteligencia Emocional/fisiología , Universidades , China , Agotamiento Psicológico , Multilingüismo , Adulto , Lenguaje , AdolescenteRESUMEN
OBJECTIVES: This pilot study aimed to prospectively investigate the effects of a wearable monitoring device, based on an Internet management platform, on the comprehensive management of type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 120 hospitalized patients with T2DM were enrolled and randomly divided into the control group and the intervention group. Patients in the control group only received conventional diabetes treatments, while patients in the intervention group were provided with a wearable monitoring device in addition to conventional diabetes treatments. Moreover, the wearable device could connect to an Internet platform for diabetes management and upload self-monitoring data. All patients were followed for 3 months. The changes in parameters representing glucose metabolism, blood lipids, renal function, and patient satisfaction were compared between the two groups. All results were analyzed on an intention-to-treat basis. RESULTS: One hundred twenty subjects met all criteria and agreed to participate in this study. During the follow-up period, 5 and 4 subjects were lost to follow-up in the intervention and control groups, respectively. Compared with the control group, the blood glucose of the intervention group decreased significantly after 3 months (p < 0.05). Subgroup analysis found that females, those younger than 60 years, with baseline glycated hemoglobin A1c (HbA1c) levels of 8% or greater, and patients with good adherence showed significant improvements in HbA1c (p < 0.05). However, there was no significant difference in blood lipid and renal function. The intervention group showed a better adherence rate to blood glucose, comprehensive adherence rate, and diabetes treatment satisfaction (p < 0.05). One subject in the intervention group and two subjects in the control group reported mild hypoglycemia. No other adverse events such as infections and skin allergies occurred in the two groups. CONCLUSION: The intervention of a wearable monitoring device based on an Internet management platform significantly improved blood glucose control in T2DM patients, as well as the overall adherence rate and patient satisfaction with treatment. CLINICAL TRIAL REGISTRATION: NCT04973644.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Satisfacción del Paciente , Dispositivos Electrónicos Vestibles , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Hemoglobina Glucada/análisis , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Glucemia/metabolismo , Anciano , Internet , Lípidos/sangre , Adulto , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificaciónRESUMEN
This study investigated whether exercise could improve the reduced HRV in an environment of high altitude. A total of 97 young, healthy male lowlanders living at 3,680 m for >1 year were recruited. They were randomized into four groups, of which three performed-low-, moderate-, and high-intensity (LI, MI, HI) aerobic exercise for 4 weeks, respectively. The remaining was the control group (CG) receiving no intervention. For HI, compared to other groups, heart rate (p = 0.002) was significantly decreased, while standard deviation of RR intervals (p < 0.001), SD2 of Poincaré plot (p = 0.046) and the number of successive RR interval pairs that differ by > 50 ms divided by total number of RR (p = 0.032), were significantly increased after intervention. For MI, significantly increase of trigonometric interpolation in NN interval (p = 0.016) was observed after exercise. Further, a decrease in systolic blood pressure (SBP) after high-intensity exercise was found significantly associated with an increase in SD2 (r = - 0.428, p = 0.042). These results indicated that there was a dose effect of different intensities of aerobic exercise on the HRV of acclimatized lowlanders. Moderate and high-intensity aerobic exercise would change the status of the autonomic nervous system (ANS) and decrease the blood pressure of acclimatized lowlanders exposed to high altitude.
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An enterprise's ownership structure is crucial for factor allocation efficiency. We used Chinese firm-level data to investigate whether changes in state-owned enterprise ownership structure contribute to resource misallocation, leading to high-quality economic development. We found a U-shaped relationship between non-state shareholding and state-owned enterprises' resource allocation efficiency. An optimal range exists for non-state shareholding. When the shareholding of non-state shareholders reaches 10%-20%, the efficiency of resource allocation is at its highest. Additional research has revealed that mixed shareholding has varying impacts on resource allocation, displaying substantial heterogeneity. These insights offer valuable guidance for future mixed-ownership reforms and serve as a practical reference for economic reforms in other nations, particularly developing countries.
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Halogenated aromatic pollutants (HAPs) including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) exhibit diverse toxicities and bio-accumulation in animals, thereby imposing risks on human via animal-derived food (ADF) consumption. Here we examined these HAPs in routine ADFs from South China and observed that PBDEs and PCBs showed statistically higher concentrations than PCDD/Fs and PBDD/Fs. PCDD/Fs and PCBs in these ADFs were mainly from the polluted feed and habitat of animals, except PCDD/Fs in egg, which additionally underwent selective biotransformation/progeny transfer after the maternal intake of PCDD/F-polluted stuff. PBDEs and PBDD/Fs were mostly derived from the extensive use of deca-BDE and their polluted environments. Significant interspecific differences were mainly observed for DL-PCBs and partly for PBDD/Fs and PBDEs, which might be caused by their distinct transferability/biodegradability in animals and the different living habit and habitat of animals. The dietary intake doses (DIDs) of these HAPs via ADF consumption were all highest for toddlers, then teenagers and adults. Milk, egg, and fish contributed most to the DIDs and risks for toddlers and teenagers, which results of several cities exceeded the recommended thresholds and illustrated noteworthy risks. Pork, fish, and egg were the top three risk contributors for adults, which carcinogenic and non-carcinogenic risks were both acceptable. Notably, PBDD/Fs showed the lowest concentrations but highest contributions to the total risks of these HAPs, thereby meriting continuous attention.
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Contaminantes Ambientales , Contaminación de Alimentos , Éteres Difenilos Halogenados , Bifenilos Policlorados , China , Animales , Humanos , Contaminación de Alimentos/análisis , Contaminación de Alimentos/estadística & datos numéricos , Éteres Difenilos Halogenados/análisis , Bifenilos Policlorados/análisis , Contaminantes Ambientales/análisis , Dibenzodioxinas Policloradas/análisis , Medición de Riesgo , Exposición Dietética/estadística & datos numéricos , Adulto , Niño , Monitoreo del Ambiente , Huevos/análisisRESUMEN
Neural style transfer is an algorithm that transfers the style of one image to another image and converts the style of the second image while preserving its content. In this paper, we propose a style transfer approach for sand painting generation based on convolutional neural networks. The proposed approach aims to improve sand painting generation via neural style transfer, which can address the problem of blurred objects. Furthermore, it can reduce background noise caused by neural style transfers. First, we segment the main objects from the content image. Subsequently, we perform close-open filtering operations on the content image to obtain smooth images. Subsequently, we perform Sobel edge detection to process the images and obtain edge maps. Based on these edge maps and the input style image, we perform neural style transfer to generate sand painting images. Finally, we integrate the generated images to obtain the final stylized sand painting image. The results show that the proposed approach yields good visual effects from sand paintings. Moreover, the proposed approach achieves better visual effects for sand painting than the previous method.
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PURPOSE: Digit-tip amputation caused by crush injury is a common emergency scenario, and the management is full of challenges. The objective of this study was to demonstrate the application of the supermicrosurgery technique in replantation procedures for complex digit-tip amputations resulting from crush injuries, while also assessing functional and aesthetic outcomes. METHODS: We conducted a retrospective analysis of the data from 12 patients who underwent replantation of 15 digits in our department between July 2022 and June 2023. The outcomes of replantation, functional recovery (including return to work, cold tolerance, bone union, DASH score, VAS score, and two-point discrimination test), aesthetic results (including digit appearance, nail deformity, and pulp atrophy), and patient satisfaction were assessed. RESULTS: The amputation of 7 digits occurred within Tamai zone I level, 8 digits within Tamai zone II level, while 4 digits occurred within Ishikawa zone I level, 3 digits within Ishikawa zone II level, 7 digits within Ishikawa zone III level, and 1 digit within Ishikawa zone IV level. The replanted digits all survived (100%) without any indications of arterial insufficiency or venous congestion. The follow-up procedures were conducted on all 12 patients, with an average duration of 9.6 months (range, 6 to 18 months). The fracture successfully underwent healing at 9.2 weeks (range, 8 to 13 weeks). The mean VAS score was 1.75 points (range 0 to 4 points), the mean two-point discrimination test result was 5.72 mm (range 4.0 to 7.0 mm), and the mean DASH score was 9.78 points (range 3.33 to 22.5 points). All patients demonstrated cold tolerance and successfully resumed their pre-injury occupational activities. The nail deformity was observed in one digit following replantation within Tamai zone I, and in three digits following replantation within Tamai zone II; moreover, eight digits exhibited varying degrees of pulp atrophy. All patients expressed satisfaction with both functional and aesthetic outcomes. CONCLUSION: The successful replantation of digit-tip amputation caused by crush injury can be achieved through the application of supermicrosurgery technique, resulting in improved functional and aesthetic outcomes. Digit-tip replantation is a favorable and meaningful procedure with high patient satisfaction.
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Nitrophenols have received extensive attention due to their strong light-absorbing ability in the near-ultraviolet-visible region, which could be influenced by the atmospheric processes of nitrophenols. However, our knowledge and understanding of the formation and evolution of nitrophenols are still in the nascent stages. In the present study, the mixing states of four mononitrophenol particles (i.e., nitrophenol, methynitrophenol, nitrocatechol, and methoxynitrophenol), and one nitropolycyclic aromatic hydrocarbon particles (i.e., nitronaphthol (NN)) were investigated using a single-particle aerosol mass spectrometer (SPAMS) in November 2019 in Qingdao, China. The results showed, for the first time, that mononitrophenols and NN exhibit different mixing states and diurnal variations. Four mononitrophenols were internally mixed well with each other, and with organic acids, nitrates, potassium, and naphthalene. The diurnal variation in the number fraction of mononitrophenols presented two peaks at 07:00 to 09:00 and 18:00 to 20:00, and a valley at noon. Atmospheric environmental conditions, including NO2, O3, relative humidity, and temperature, can significantly influence the diurnal variation of mononitrophenols. Multiple linear regression and random forest regression models revealed that the main factors controlling the diurnal variation of mononitrophenols were photochemical reactions during the day and aqueous-phase reactions during the night. Unlike mononitrophenols, about 62-83% of NN were internally mixed with [NH4]+ and [H(NO3)2]-, but not with organic acids and potassium. The diurnal variation of NN was also different from that of mononitrophenols, generally increased from 17:00 to 10:00 and then rapidly decreaed from 11:00 to 16:00. These results imply that NN may have sources and atmospheric processes that are different from mononitrophenols. We speculate that this is mostly controlled by photochemical reactions and mixing with [NH4]+, which may influence the diurnal variation of NN in the ambient particles; however, this requires further confirmation. These findings extend our current understanding of the atmospheric formation and evolution of nitrophenols.
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Contaminantes Atmosféricos , Nitrofenoles , Potasio , Ritmo Circadiano , Antifúngicos , China , Polvo , Aerosoles , Monitoreo del Ambiente , Material Particulado , Estaciones del AñoRESUMEN
BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).
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COVID-19 , Inhibidores de Proteasa de Coronavirus , Adulto , Humanos , Administración Oral , Antivirales/administración & dosificación , Antivirales/efectos adversos , Antivirales/farmacología , Antivirales/uso terapéutico , China , Proteínas M de Coronavirus/antagonistas & inhibidores , Proteínas M de Coronavirus/metabolismo , Inhibidores de Proteasa de Coronavirus/administración & dosificación , Inhibidores de Proteasa de Coronavirus/efectos adversos , Inhibidores de Proteasa de Coronavirus/farmacología , Inhibidores de Proteasa de Coronavirus/uso terapéutico , COVID-19/metabolismo , COVID-19/terapia , Tratamiento Farmacológico de COVID-19/métodos , Método Doble Ciego , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Ritonavir/farmacología , Ritonavir/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Factores de Tiempo , Combinación de MedicamentosRESUMEN
Fluorinated liquid crystal monomers (FLCMs) have been suggested as emerging contaminants, raising global concern due to their frequent occurrence, potential toxic effects, and endurance capacity in the environment. However, the environmental fate of the FLCMs remains unknown. To fill this knowledge gap, we investigated the aerobic microbial transformation mechanisms of an important FLCM, 4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3, 5-difluoro-4'-propylbiphenyl (DTMDPB), using an enrichment culture termed as BG1. Our findings revealed that 67.5 ± 2.1% of the initially added DTMDPB was transformed in 10 days under optimal conditions. A total of 14 microbial transformation products obtained due to a series of reactions (e.g., reductive defluorination, ether bond cleavage, demethylation, oxidative hydroxylation and aromatic ring opening, sulfonation, glucuronidation, O-methylation, and thiolation) were identified. Consortium BG1 harbored essential genes that could transform DTMDPB, such as dehalogenation-related genes [e.g., glutathione S-transferase gene (GST), 2-haloacid dehalogenase gene (2-HAD), nrdB, nuoC, and nuoD]; hydroxylating-related genes hcaC, ubiH, and COQ7; aromatic ring opening-related genes ligB and catE; and methyltransferase genes ubiE and ubiG. Two DTMDPB-degrading strains were isolated, which are affiliated with the genus Sphingopyxis and Agromyces. This study provides a novel insight into the microbial transformation of FLCMs. The findings of this study have important implications for the development of bioremediation strategies aimed at addressing sites contaminated with FLCMs.
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Cristales Líquidos , Biodegradación Ambiental , HidroxilaciónRESUMEN
BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) exhibit glucose-lowering, weight-reducing, and blood pressure-lowering effects. Nevertheless, a debate exists concerning the association between GLP-1RA treatment and the risk of diabetic retinopathy (DR) in patients diagnosed with type 2 diabetes mellitus (T2DM). OBJECTIVE: To ascertain the risk of DR in patients with T2DM undergoing GLP-1RA treatment, we conducted a meta-analysis utilizing data derived from randomized placebo-controlled studies (RCTs). METHODS: A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, and EMBASE. We focused on RCTs involving the use of GLP-1RAs in patients with T2DM. Utilizing R software, we compared the risk of DR among T2DM patients undergoing GLP-1RA treatment. The Cochrane risk of bias method was employed to assess the research quality. RESULTS: The meta-analysis incorporated data from 20 RCTs, encompassing a total of 24,832 T2DM patients. Across all included trials, randomization to GLP-1 RA treatment did not demonstrate an increased risk of DR (odds ratio = 1.17; 95% CI 0.98-1.39). Furthermore, no significant heterogeneity or publication bias was detected in the analysis. CONCLUSION: The results of this systematic review and meta-analysis indicate that the administration of GLP-1 RA is not associated with an increased risk of DR. PROSPERO REGISTRATION IDENTIFIER: CRD42023413199.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Retinopatía Diabética/epidemiología , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Agonistas Receptor de Péptidos Similares al Glucagón , Hipoglucemiantes/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
End-of-life vehicles (ELVs) dismantling sites are the notorious hotspots of chlorinated organophosphate esters (Cl-OPEs). However, the microbial-mediated dechlorination of Cl-OPEs at such sites has not yet been explored. Herein, the dechlorination products, pathways and mechanisms of tris(2-chloroethyl) phosphate (TCEP, a representative Cl-OPE) by an anaerobic enrichment culture (ZNE) from an ELVs dismantling plant were investigated. Our results showed that dechlorination of TCEP can be triggered by reductive transformation to form bis(2-chloroethyl) phosphate (BCEP), mono-chloroethyl phosphate (MCEP) and by hydrolytic dechlorination to form bis(2-chloroethyl) 2-hydroxyethyl phosphate (TCEP-OH), 2-chloroethyl bis(2-hydroxyethyl) phosphate (TCEP-2OH), 2-chloroethyl (2-hydroxyethyl) hydrogen phosphate (BCEP-OH). The combination of 16S rRNA gene amplicon sequencing, quantitative real-time PCR (qPCR) and metagenomics revealed that the Dehalococcoides played an important role in the reductive transformation of TCEP to BCEP and MCEP. A high-quality metagenome-assembled genome (completeness >99% and contamination <1%) of Dehalococcoides was obtained. The sulfate-reducing bacteria harboring haloacid dehalogenase genes (had) may be responsible for the hydrolytic dechlorination of TCEP. These findings provide insights into microbial-mediated anaerobic transformation products and mechanisms of TCEP at ELVs dismantling sites, having implications for the environmental fate and risk assessment of Cl-OPEs at those sites.
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Retardadores de Llama , Anaerobiosis , ARN Ribosómico 16S/genética , Retardadores de Llama/análisis , Organofosfatos , Fosfatos/análisis , Ésteres , ChinaRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) is a major type of lung cancer worldwide, and under the pandemic coronavirus disease 2019 (COVID-19), its cancer burden is enlarged. This study aimed to explore potential drug targets and potential drugs for developing effective treatments for patients with both lung cancer and COVID-19. METHOD: The interaction network of molecule compounds-target genes was constructed based on Traditional Chinese Medicines (TCMs) and gene expression data from public databases. The potential effectiveness of drugs was analyzed by molecular docking and molecular dynamics simulation. Western blot, transfection assay, Immunohistochemistry (IHC) staining, and flow cytometry were performed to investigate the function of HSP90AA1 in LUAD cells. RESULT: Eight target genes (GSK3B, HMOX1, HSP90AA1, ICAM1, MAPK1, PLAU, RELA and TNFSF15.) were identified, and two of them (HSP90AA1 and RELA) were significantly associated with LUAD prognosis. Luteolin was discovered to bind with HSP90AA1. Moreover, In vitro cell experiments demonstrated that HSP90AA1 had higher expression in A549 cells, promoted cell viability and suppressed apoptosis in A549 cells and H1299 cells. CONCLUSION: HSP90AA1 was a target gene for further designing effective drugs for LUAD patients. Luteolin was a potential drug for treating patients with both LUAD and COVID-19.
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Municipal solid waste incinerator (MSWI) not only is deemed one of the uppermost sources of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), but also produces substantial amount of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) owing to the existence of brominated flame retardants (BFRs) in the waste. So far, however, PBDD/Fs in the vicinal environments of MSWI and their associated risks remain rarely studied. Based on a one-year passive air sampling (PAS) scheme, we investigated airborne PBDD/Fs and PCDD/Fs around a large-scale MSWI that has been operated for multi-years. Both the concentrations of PBDD/Fs and PCDD/Fs showed spatially decreasing trends with the distance away from the MSWI, confirming the influence of the MSWI on the dioxin levels in its ambient air. But its influence on PBDD/Fs was less because PBDD/Fs exhibit lower volatility and therefore lower gaseous concentrations than PCDD/Fs. Compared to the existing global data of airborne PCDD/Fs and PBDD/Fs, our data of the MSWI vicinity were at medium levels, despite PAS samples only represent the concentrations of gaseous dioxins in theory. The seasonal data suggest that meteorological conditions exerted apparent influences over the concentrations and sources of airborne dioxins around the MSWI. As for PCDD/Fs, the MSWI was diagnosed as their uppermost source, followed by local traffic and volatilization/deposition. Whereas the top three PBDD/F sources were related to PBDEs, bromophenol/bromobenzene, and traffic vehicles, respectively. The bioassay-derived TEQs based on the aryl hydrocarbon receptor activation of airborne dioxins around the MSWI were one or two orders of magnitudes higher than their concentration-based TEQs, and the corresponding carcinogenic risks at some MSWI-vicinal sites exceeded the acceptable threshold proposed by the U. S. EPA (10-6 â¼ 10-4) and deserve continuous attention.
Asunto(s)
Contaminantes Atmosféricos , Dioxinas , Dibenzodioxinas Policloradas , Dioxinas/análisis , Dibenzodioxinas Policloradas/análisis , Residuos Sólidos , Dibenzofuranos/análisis , Carcinógenos , Monitoreo del Ambiente , Muestreo , Contaminantes Atmosféricos/análisis , Incineración , Gases/análisis , Dibenzofuranos Policlorados/análisisRESUMEN
Gastric cancer (GC) is a common malignant tumor, posing a great threat to human's health and life. Previous studies have suggested aberrant expression of long non-coding RNAs (lncRNAs) in GC. This study elucidated the effects of lncRNA ACTA2-AS1 on the biological characteristics of GC. Gene expression in stomach adenocarcinoma (STAD) samples compared with normal tissues and the correlation between gene expression and prognosis of STAD patients were analyzed using bioinformatic tools. Gene expression at protein and mRNA levels in GC and normal cells was tested by western blotting and RT-qPCR. The subcellular localization of ACTA2-AS1 in AGS and HGC27 cells was identified by nuclear-cytoplasmic fractionation and FISH assay. EdU, CCK-8, flow cytometry analysis, TUNEL staining assays were conducted to evaluate the role of ACTA2-AS1 and ESRRB on GC cellular behaviors. The binding relationship among ACTA2-AS1, miR-6720-5p and ESRRB was verified by RNA pulldown, luciferase reporter assay and RIP assay. LncRNA ACTA2-AS1 was underexpressed in GC tissues and cell lines. ACTA2-AS1 elevation suppressed GC cell proliferation and induced apoptosis. Mechanistically, ACTA2-AS1 directly bound to miR-6720-5p and subsequently promoted the expression of target gene ESRRB in GC cells. Furthermore, ESRRB knockdown reversed the influence of ACTA2-AS1 overexpression on GC proliferation and apoptosis. ACTA2-AS1 plays an antioncogenic role in GC via binding with miR-6720-5p to regulate ESRRB expression.