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The presence of emerging contaminants (ECs) in drinking water sources is an increasing concern, yet limited data exists on their occurrence and risk in the upper Huaihe River Basin, an important agricultural region in Central China. This study investigated 70 ECs, including pesticide and antibiotics in surface water from drinking water source areas in Nanwan Reservoir along the upper reaches of the Huaihe River Basin to prioritize the ECs based on ecological risk and health risk assessment. A total of 66 ECs were detected in the surface water at least once at the selected 38 sampling sites, with concentrations ranging from 0.04 to 2508 ng/L. Ecological risk assessment using the risk quotient (RQ) method revealed high risks (RQ > 1) from 7 ECs in the dry season and 15 ECs in the wet season, with triazine pesticides as the main contributors. Non-carcinogenic risks were below negligible levels, but carcinogenic risks from neonicotinoid and carbamate pesticides and macrolide antibiotics were concerning for teenagers. Ciprofloxacin exhibited a high level of resistance risk during the wet season. A multi-indicator prioritization approach integrating occurrence, risk, and chemical property data ranked 6 pesticides and 3 antibiotics as priority pollutants. The results highlight EC contamination of drinking water sources in this agriculturally-intensive region and the need for targeted monitoring and management to protect water quality.
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BACKGROUND: Helicobacter pylori (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%. The multidrug resistance of HP poses a serious challenge to eradication. It has been de-monstrated that compared to bismuth quadruple therapy, Qingre Huashi decoction (QHD) combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions; in addition, QHD can directly inhibit and kill HP in vitro. AIM: To explore the effect and mechanism of QHD on clinically multidrug-resistant and strong biofilm-forming HP. METHODS: In this study, 12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients. In vitro, the minimum inhibitory concentration (MIC) values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining, respectively. The most robust biofilm-forming strain of HP was selected, and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation. This assessment was performed using agar dilution, E-test, killing dynamics, and transmission electron microscopy (TEM). The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation. Crystalline violet method, scanning electron microscopy, laser confocal scanning microscopy, and (p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains. The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction. Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups. RESULTS: HP could form biofilms of different degrees in vitro, and the intensity of formation was associated with the drug resistance of the strain. QHD had strong bacteriostatic and bactericidal effects on HP, with MICs of 32-64 mg/mL. QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains, disrupt the biofilm structure, lower the accumulation of (p)ppGpp, decrease the expression of biofilm-related genes including LuxS, Spot, glup (HP1174), NapA, and CagE, and reduce the expression of efflux pump-related genes such as HP0605, HP0971, HP1327, and HP1489. Based on metabolomic analysis, QHD induced oxidative stress in HP, enhanced metabolism, and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate (AMP), thereby affecting HP growth, metabolism, and protein synthesis. CONCLUSION: QHD exerts bacteriostatic and bactericidal effects on HP, and reduces HP drug resistance by inhibiting HP biofilm formation, destroying its biofilm structure, inhibiting the expression of biofilm-related genes and efflux pump-related genes, enhancing HP metabolism, and activating AMP in HP.
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Antibacterianos , Biofilmes , Medicamentos de Ervas Chinesas , Infecções por Helicobacter , Helicobacter pylori , Testes de Sensibilidade Microbiana , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Biofilmes/efeitos dos fármacos , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , GastroscopiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori (H. pylori) infections are on the rise, presenting a significant global health challenge. Mass Galla chinesis et camelliae Fermentata (Chinese gall leaven, CGL), a traditional Chinese medicinal product made from the fermentation of Rhus chinensis Mill., is frequently employed to address digestive system ailments. Contemporary pharmacological research reveals that CGL exhibits anti-inflammatory, anti-diarrheal, and enzyme-inhibitory activities and holds potential as a treatment for H. pylori infections. However, the precise mechanisms underlying CGL's efficacy against H. pylori remain to be fully elucidated. AIM: The objective of the study is to evaluate CGL's ability to disrupt the H. pylori biofilm and to explore its synergistic potential with antibiotics in targeting the biofilm-efflux pump system, a mechanism implicated in bacterial resistance. METHORDS: The study determined the Minimum Inhibitory Concentration (MIC) of CGL and metronidazole against H. pylori and evaluated their effects on H. pylori biofilms using an in vitro model. Structural changes induced by drug interventions were compared to those in untreated and antibiotic-treated models through scanning electron microscopy and laser confocal microscopy. The accumulation of H33342 dye in planktonic and biofilm H. pylori before and after drug treatment was assessed to evaluate cell viability and biofilm disruption. The study also involved adding experimental drugs to a biofilm H. pylori medium containing D-glucose, measuring glucose concentrations post-intervention using the glucose oxidase method, and calculating changes in glucose uptake. Finally, the relative expression levels of several genes in planktonic and biofilm H. pylori treated with CGL alone or in combination with antibiotics were measured to understand the impact on the biofilm-efflux pump system. RESULTS: Both CGL alone and in combination with metronidazole demonstrated effective disruption of H. pylori biofilms. The combination therapy was particularly effective in reducing the biofilm transfer-enhancing effect of metronidazole and decreasing SpoT expression in the 'SpoT-(p)ppGpp' pathway, especially in biofilms. It showed a greater inhibition of the 'σ54-gluP-sugar uptake' pathway, with significant reductions in rpoN and gluP expression under biofilm conditions compared to CGL or metronidazole alone. The treatment also suppressed H. pylori proliferation and may have altered glucose uptake mechanisms. Moreover, it significantly inhibited the 'hp0939/hp0497/hp0471-RND efflux pump' pathway, with a notable reduction in gene expression compared to the 1/2 MIC metronidazole treatment. CONCLUSION: This study demonstrates that CGL effectively hinders the development of drug resistance in H. pylori by targeting biofilm formation and critical molecular pathways associated with antibiotic resistance. The synergistic effect of combining CGL with metronidazole notably enhances biofilm disruption and inhibits the bacterium's metabolic and reparative mechanisms. Further in vivo studies are needed to confirm these results and to investigate additional mechanisms of CGL's action.
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Antibacterianos , Biofilmes , Helicobacter pylori , Testes de Sensibilidade Microbiana , Biofilmes/efeitos dos fármacos , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/farmacologia , Metronidazol/farmacologia , Rhus/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Extratos Vegetais/farmacologia , Medicamentos de Ervas Chinesas , TaninosRESUMO
BACKGROUND AND AIMS: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. METHODS: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. RESULTS: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modiï¬ed intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). CONCLUSIONS: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. TRIAL REGISTRATION NUMBER: ChiCTR2300074693.
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Antibacterianos , Hipersensibilidade a Drogas , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Penicilinas , Pirróis , Sulfonamidas , Tetraciclina , Humanos , Sulfonamidas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Hipersensibilidade a Drogas/etiologia , Tetraciclina/uso terapêutico , Tetraciclina/efeitos adversos , Tetraciclina/administração & dosagem , Penicilinas/efeitos adversos , Penicilinas/uso terapêutico , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Pirróis/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Adulto , Bismuto/uso terapêutico , Bismuto/efeitos adversos , Bismuto/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento , Idoso , Metronidazol/efeitos adversos , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Lansoprazol/uso terapêutico , Lansoprazol/administração & dosagem , Lansoprazol/efeitos adversosRESUMO
PURPOSE: Multifaceted factors contribute to inferior outcomes following anterior cruciate ligament (ACL) reconstruction surgery. A particular focus is placed on the posterior tibial slope (PTS). This study introduces the integration of machine learning and artificial intelligence (AI) for efficient measurements of tibial slopes on magnetic resonance imaging images as a promising solution. This advancement aims to enhance risk stratification, diagnostic insights, intervention prognosis and surgical planning for ACL injuries. METHODS: Images and demographic information from 120 patients who underwent ACL reconstruction surgery were used for this study. An AI-driven model was developed to measure the posterior lateral tibial slope using the YOLOv8 algorithm. The accuracy of the lateral tibial slope, medial tibial slope and tibial longitudinal axis measurements was assessed, and the results reached high levels of reliability. This study employed machine learning and AI techniques to provide objective, consistent and efficient measurements of tibial slopes on MR images. RESULTS: Three distinct models were developed to derive AI-based measurements. The study results revealed a substantial correlation between the measurements obtained from the AI models and those obtained by the orthopaedic surgeon across three parameters: lateral tibial slope, medial tibial slope and tibial longitudinal axis. Specifically, the Pearson correlation coefficients were 0.673, 0.850 and 0.839, respectively. The Spearman rank correlation coefficients were 0.736, 0.861 and 0.738, respectively. Additionally, the interclass correlation coefficients were 0.63, 0.84 and 0.84, respectively. CONCLUSION: This study establishes that the deep learning-based method for measuring posterior tibial slopes strongly correlates with the evaluations of expert orthopaedic surgeons. The time efficiency and consistency of this technique suggest its utility in clinical practice, promising to enhance workflow, risk assessment and the customization of patient treatment plans. LEVEL OF EVIDENCE: Level III, cross-sectional diagnostic study.
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2-methylisoborneol (2-MIB), a secondary metabolite produced by cyanobacteria, often causes a musty odour in water, threatening the safety of drinking water supplies. This study investigated the effects of the growth phases on the production of 2-MIB by Pseudanabaena. The effects of cell characteristics on the production and release of 2-MIB were also explored. The total 2-MIB concentration increased during the exponential phase and decreased during the declining phase, which was consistent with the changes in cell density. However, the total 2-MIB yield (1.12-1.27 fg cell-1) of Pseudanabaena did not significantly differ throughout the growth cycle (p > 0.05). Meanwhile, the extracellular 2-MIB yield increased significantly from 0.31 fg cell-1 in the exponential phase to 0.76 fg cell-1 in the declining phase (p < 0.05), and the corresponding proportion of extracellular 2-MIB improved from 25.13% to 59.16% (p < 0.05). The surge in extracellular 2-MIB during the declining phase could be attributed to the breaking of the Pseudanabaena filament, as indicated by the decrease in Dmean during cell ageing. The findings of this study contribute to a more inclusive comprehension and management of musty odour issues resulting from cyanobacteria in the water supply.
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Cianobactérias , Cianobactérias/metabolismo , Abastecimento de Água , OdorantesRESUMO
Positively charged bubbles efficiently capture and remove negatively charged algal cells without relying on coagulation-flocculation. However, the efficiency is notably influenced by the presence of algal organic matter (AOM). This study investigated the impact of AOM composition on flotation performance by analyzing AOM from various growth phases of Microcystis flos-aquae. The results indicated that low-concentration AOM (<5 mg C L-1), particularly the high molecular weight (>30 kDa) fractions containing high percentages of protein during the exponential growth phase, significantly improved the flotation efficiency by >18%. A high-speed camera system illustrates the pivotal role of low-concentration protein-containing AOM in forming network structures that enhance cell capture. These protein-driven network structures, which enhance the flotation efficiency, provide valuable insights into the development of effective in-situ algal bloom prevention techniques.
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Microcystis , Microcystis/metabolismo , Eutrofização , FloculaçãoRESUMO
The efficiency of mixotrophic microalgae in enhancing the recovery of waste nutrients has been well established; however, the recovery rate is crucial in meeting the needs of field applications. This study evaluated the impact of media characteristics on nutrient recovery under mixotrophic conditions. The mixotrophic N recovery rate with S. acuminatus in modified BG-11 reached 2.59 mg L-1h-1. A mixotrophic growth optimization strategy was applied to achieve a high-rate nutrient recovery from municipal wastewater treatment plant effluents. The contribution of waste chemical oxygen demand (COD) to nutrient recovery was assessed using secondary effluent (SE) under heterotrophy. The results highlighted a significant increase in total nitrogen (TN) and total phosphorus (TP) recovery rates when glucose was supplied, indicating the additional carbon requirements for efficient nutrient recovery. The TN and TP recovery rates under mixotrophic conditions with the addition of trace metals and high cell density were enhanced by 91.94% and 92.53%, respectively, resulting in recovery rates of 3.43 mg L-1h-1 and 0.30 mg L-1h-1. The same conditions were used for nutrient recovery from primary effluent (PE), and the results were more satisfactory as the TN and TP recovery rates reached 4.79 and 0.55 mg L-1h-1, respectively. Additionally, the study estimated the carbon footprints (C-footprints) and areal footprints of mixotrophy-based nitrogen recovery. The findings revealed carbon footprints and areal footprints of -15.93 ± 4.57 tCO2e t-1 N recovery and 0.53 ± 0.19 m3 m-2d-1 wastewater, respectively. This high-rate nutrient recovery, achieved under a carbon-negative (C-negative) budget through mixotrophy, presents a novel strategy for efficiently recovering resources from municipal wastewater, thus facilitating resource recycling and ensuring environmental sustainability.
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Microalgas , Scenedesmus , Águas Residuárias , Carbono , Biomassa , Fósforo , Nutrientes , NitrogênioRESUMO
Background: Helicobacter pylori (HP) is considered a leading risk factor for gastric cancer (GC). The aim of this article is to conduct bibliometric and visual analysis to assess scientific output, identify highly cited papers, summarize current knowledge, and explore recent hotspots and trends in HP/GC research. Methods: A bibliographic search was conducted on October 24, 2023, to retrieve relevant studies on HP/GC research between 2003 and 2022. The search terms were attached to HP and GC. The main data were from the Web of Science Core Collection (WoSCC). Data visualization was performed using Biblioshiny, VOSviewer, and Microsoft Excel. Results: In HP/GC research, 1970 papers were retrieved. The total number of papers (Np) in HP/GC was growing from 2003 to 2022. China and Japan were in the leading position and made the most contributions to HP/GC. Vanderbilt University and the US Department of Veterans Affairs had the highest Np. The most productive authors were Peek Jr Richard M. and Piazuelo M Blanca. Helicobacter received the most Np, while Gastroenterology had the most total citations (TC). High-cited publications and keyword clustering were used to identify the current status and trends in HP/GC research, while historical citation analysis provided insight into the evolution of HP/GC research. The hot topics included the effect of HP on gastric tumorigenesis and progression, the pathogenesis of HP-induced GC (HP factors), and the mechanisms by which HP affects GC (host factors). Research in the coming years could focus on topics such as autophagy, gut microbiota, immunotherapy, exosomes, epithelial-mesenchymal transition (EMT), and gamma-glutamyl transpeptidase (GGT). Conclusion: This study evaluated the global scientific output in HP/GC research and its quantitative characteristics, identified the essential works, and collected information on the current status, main focuses and emerging trends in HP/GC research to provide academics with guidance for future paths.
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Helicobacter pylori , Neoplasias Gástricas , Humanos , Fenômenos Fisiológicos Celulares , AutofagiaRESUMO
To cope with the shuttling of soluble lithium polysulfides in lithium-sulfur batteries, confinement tactics, such as trapping of sulfur within porous carbon structures, have been extensively studied. Although performance has improved a bit, the slow polysulfide conversion inducing fast capacity decay remains a big challenge. Herein, a NiS2/carbon (NiS2/C) composite with NiS2 nanoparticles embedded in a thin layer of carbon over the surface of micro-sized hollow structures has been prepared from Ni-metal-organic frameworks. These unique structures can physically entrap sulfur species and also influence their redox conversion kinetics. By improving the reaction kinetics of polysulfides, the NiS2/carbon@sulfur (NiS2/C@S) composite cathode with a suppressed shuttle effect shows a high columbic efficiency and decent rate performance. An initial capacity of 900 mAh g-1 at the rate of 1 C (1 C = 1675 mA g-1) and a low-capacity decline rate of 0.132% per cycle after 500 cycles are obtained, suggesting that this work provides a rational design of a sulfur cathode.
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Harmful algal blooms, particularly those of Microcystis aeruginosa, present significant ecological and health risks. To address this issue, this study utilized a custom static algal growth assessment apparatus to investigate the anti-algal performance of a copper-alloyed 316L stainless steel (SS), named 316L-Cu SS. This material was compared with traditional 316L SS, which is widely utilized in freshwater systems for its corrosion resistance. Algal growth dynamics were monitored through optical density (OD) and chlorophyll A concentration measurements. Notably, 316L-Cu SS exhibited superior inhibitory effects on Microcystis aeruginosa growth compared to 316L SS and control groups. Inductively coupled plasma mass spectrometry (ICP-MS) confirmed that the copper ion release from 316L-Cu SS played a critical role in this algal suppression, which interfered with photosynthesis, induced oxidative stress, and damaged algal cell membranes. In contrast, other metal ions (Ni, Cr, Fe) had a negligible impact on algal growth. The study highlights 316L-Cu SS as a promising material for mitigating harmful algal blooms, thereby offering potential benefits for both aquatic ecosystem conservation and public health protection.
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Cianobactérias , Microcystis , Cobre/química , Aço Inoxidável/química , Clorofila A , EcossistemaRESUMO
Foam flotation is generally recognized as a low-cost and efficient technology for the harvesting of microalgae for food, feed and fuel production, as well as environmental remediation. However, the harvesting efficiency of microalgae using foam flotation is restricted by the residual metal cations in the medium, and the corresponding inhibition mechanism has not yet been revealed. This study investigated the effects of metal cations in the medium on the harvesting efficiency and concentration factor during the foam flotation of Scenedesmus acuminatus. The interface interaction of cell-collector-bubble effected by metal cations was revealed by quantifying the amount of collector (cetyl trimethylammonium bromide, CTAB) between cells and bubbles, as well as the response of bubble interface characteristics. Results showed that the harvesting efficiency dropped linearly as the increase of cationic concentrations. Under the CTAB dose of 20 mg L-1, the harvesting efficiency decreased from 98.65% to 56.77% with a decrease of concentration factor from 25.41 to 9.05 in the presence of metal cations. The Na+ and Mg2+ in the medium were the major inhibitors. The inhibitory mechanisms revealed that metal cations obviously impeded the adsorption of CTAB onto the cells by competing adsorption site, resulting in a low harvesting efficiency. The presence of metal cations also inhibited the bubble coalescence and slowed down drainage velocity in the plateau channel of foam layer, forming foam with higher water content, thus reducing the concentration factor. A schematic illustration is proposed to better understand the effect mechanism of metal cations on microalgal foam flotation. This study might facilitate the process development in an effort to overcome the inhibition of cations during microalgal foam flotation.
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Microalgas , Cetrimônio , Metais , CátionsRESUMO
BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. RESULTS: Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p < 0.001]. Circulating PCSK9 levels positively correlated with CHD severity (diseased vessels: r = 0.35, p < 0.001; Gensini score: r = 0.46, p < 0.001). Elevated PCSK9 levels are an independent risk factor for CHD risk and severity (CHD group vs. non-CHD group: OR = 2.829, 95% CI: 1.771-4.520, p < 0.001; three vessel disease group vs. one vessel disease group: OR = 4.800, 95% CI: 2.387-9.652, p < 0.001; high GS group vs. low GS group: OR = 5.534, 95% CI: 2.733-11.208, p < 0.001). Through a six-year follow-up and multivariate Cox regression analysis, elevated circulating PCSK9 levels were found to be independently associated with MACEs in all participants (HR: 3.416, 5% CI: 2.485-4.697, p < 0.001; adjusted HR: 2.780, 95% CI: 1.930-4.004, p < 0.001). CONCLUSIONS: Serum PCSK9 levels were positively correlated with multi-vessel CHD and Gensini score. Elevated circulating PCSK9 levels are an independent risk factor for CHD and increased incidence of MACEs in T2DM.
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Observational studies have shown that the gut microbiome is associated with frailty. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between the genetically predicted gut microbiome and frailty using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from a genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We used LDSC and MR analyses to estimate the genetic correlation and causality between the genetically predicted gut microbiome and frailty. Our findings indicate a suggestive genetic correlation between Christensenellaceae R-7 and frailty. Moreover, we found evidence for suggestive causal effects of twelve genus-level gut microbes on frailty using at least two MR methods. There was no evidence of horizontal pleiotropy or heterogeneity in the MR analysis. This study provides suggestive evidence for a potential genetic correlation and causal association between several genetically predicted gut microbes and frailty. More population-based observational studies and animal experiments are required to clarify this association and the underlying mechanisms.
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Fragilidade , Microbioma Gastrointestinal , Fragilidade/genética , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , HumanosRESUMO
Objectives: Patients with digestive diseases frequently suffer from dyspepsia and malabsorption, which may lead to muscle loss due to malnutrition. However, it is not clear whether digestive diseases are associated with sarcopenia. This study aims to explore the longitudinal association between digestive diseases and sarcopenia in middle-aged and older adults based on a nationally representative survey from China. Methods: We used a prospective cohort study including 7,025 middle-aged and older adults aged ≥45 years from the 2011 to 2015 waves China Health and Retirement Longitudinal Study (CHARLS). Digestive diseases were identified using self-report. The assessment of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 Consensus and included three components of muscle strength, physical performance, and muscle mass. Cox hazards regression was used to examine the association between digestive diseases and sarcopenia. Results: The prevalence of digestive diseases and the incidence of sarcopenia in middle-aged and older adults were 22.6% (95% CI = 21.6-23.6%) and 8.5% (95% CI = 7.8-9.1%). After adjusting for 15 covariates composed of three sets (demographic characteristics, lifestyles, and health status), digestive diseases were associated with a higher risk of sarcopenia (HR = 1.241, 95% CI = 1.034-1.490, P < 0.05). The associations were more pronounced among men, older adults aged 60-79, rural residents, and married people. In addition, the association between digestive diseases and sarcopenia was robust in the sensitivity analysis. Conclusion: Digestive diseases were associated with an increased risk of sarcopenia in middle-aged and older adults aged ≥45 years. Early intervention of digestive diseases may help to reduce the incidence of sarcopenia in middle-aged and older adults.
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Some mixotrophic microalgae appear to exceed the sum of photoautotrophy and heterotrophy in terms of biomass production. This paper mainly reviews the carbon and energy metabolism of microalgae to reveal the synergistic mechanisms of the mixotrophic mode from multiple aspects. It explains the shortcomings of photoautotrophic and heterotrophic growth, highlighting that the mixotrophic mode is not simply the sum of photoautotrophy and heterotrophy. Specifically, microalgae in mixotrophic mode can be divided into separate parts of photoautotrophic and heterotrophic cultures, and the synergistic parts of photoautotrophic culture enhance aerobic respiration and heterotrophic culture enhance the Calvin cycle. Additionally, this review argues that current deficiencies in mixotrophic culture can be improved by uncovering the synergistic mechanism of the mixotrophic mode, aiming to increase biomass growth and improve quality. This approach will enable the full utilization of advantagesin various fields, and provide research directions for future microalgal culture.
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Microalgas , Microalgas/metabolismo , Carbono/metabolismo , Processos Heterotróficos , Fotossíntese , Biomassa , Metabolismo EnergéticoRESUMO
BACKGROUND: Ferroptosis is iron-dependent non-apoptotic cell death, that is characterized by the excessive accumulation of lipid peroxides. Ferroptosis-inducing therapy also shows promise in the treatment of cancers. However, ferroptosis-inducing therapy for glioblastoma multiforme (GBM) is still in the exploratory stage. METHODS: We identified the differentially expressed ferroptosis regulators using Mann-Whitney U test in the proteome data from Clinical Proteomic Tumor Analysis Consortium (CPTAC). We next analyzed the effect of mutation on protein abundance. A multivariate Cox model was constructed to identify the prognostic signature. RESULTS: In this study, we systemically portrayed the proteogenomic landscape of ferroptosis regulators in GBM. We observed that some mutation-specific ferroptosis regulators, such as down-regulated ACSL4 in EGFR-mutated patients and up-regulated FADS2 in IDH1-mutated patients, were linked to the inhibited ferroptosis activity in GBM. To interrogate the valuable treatment targets, we performed the survival analysis and identified five ferroptosis regulators (ACSL3, HSPB1, ELAVL1, IL33, and GPX4) as the prognostic biomarkers. We also validated their efficiency in external validation cohorts. Notably, we found overexpressed protein and phosphorylation abundances of HSPB1 were poor prognosis markers for overall survival of GBM to inhibit ferroptosis activity. Alternatively, HSPB1 showed a significant association with macrophage infiltration levels. Macrophage-secreted SPP1 could be a potential activator for HSPB1 in glioma cells. Finally, we recognized that ipatasertib, a novel pan-Akt inhibitor, could be a potential drug for suppressing HSPB1 phosphorylation, inducing ferroptosis of glioma cells. CONCLUSION: In summary, our study characterized the proteogenomic landscape of ferroptosis regulators and identified that HSPB1 could be a candidate target for ferroptosis-inducing therapy strategy for GBM.
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Ferroptose , Glioblastoma , Glioma , Proteogenômica , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Ferroptose/genética , ProteômicaRESUMO
Background: Increasing evidence has shown that the intestinal microbiome (IM) is highly linked to colorectal cancer (CRC). To investigate scientific output, identify highly cited papers, and explore research hotspots and trends in the field of IM/CRC, we conducted a bibliometric and visualized analysis. Methods: A bibliographic search regarding IM/CRC research (2012-2021) was implemented on October 17, 2022. The terms attached to IM and CRC were searched for in the titles (TI), abstracts (AB), and author keywords (AK). The main information was extracted from the Web of Science Core Collection (WoSCC). Biblioshiny from R packages and VOSviewer were used for data visualization. Results: A total of 1725 papers related to IM/CRC were retrieved. Publications on IM/CRC have grown rapidly from 2012 to 2021. China and the United States were in the leading position for publications in this field and made the most significant contributions to IM/CRC research. Shanghai Jiao Tong University and Harvard University were the most productive institutions. The high-yield authors were Yu Jun and Fang Jing Yuan. The International Journal of Molecular Sciences published the most papers, whereas Gut had the most citations. Historical citation analysis showed the evolution of IM/CRC research. Current status and hotspots were highlighted using keyword cluster analysis. The hot topics include the effect of IM on tumorigenesis, the effect of IM on CRC treatment, the role of IM in CRC screening, the mechanisms of IM involvement in CRC, and IM modulation for CRC management. Some topics, such as chemotherapy, immunotherapy, Fusobacterium nucleatum and short-chain fatty acids could be the focus of IM/CRC research in the coming years. Conclusion: This research evaluated the global scientific output of IM/CRC research and its quantitative features, identified some significant papers, and gathered information on the status and trends of IM/CRC research, which may shape future paths for academics and practitioners.
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Microbioma Gastrointestinal , Neoplasias , Humanos , China , Fenômenos Fisiológicos Celulares , Reações Cruzadas , BibliometriaRESUMO
BACKGROUND: The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin. OBJECTIVE: To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies. DESIGN: Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13 C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing. RESULTS: A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline. CONCLUSIONS: For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Hipersensibilidade , Humanos , Infecções por Helicobacter/tratamento farmacológico , Amoxicilina/uso terapêutico , Estudos de Viabilidade , Antibacterianos/uso terapêutico , Tetraciclina/uso terapêutico , Penicilinas/uso terapêutico , Quimioterapia Combinada , Resultado do Tratamento , Claritromicina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
Co-coagulation flotation (CCF) is a novel flotation technology that renders more efficient algal removal compared to traditional mechanical coagulation flotation (MCF) due to a short residence time (< 30 s) and fast rising behavior of algal flocs (> 250 m·h-1). This study compared the algal removal performance using continuous CCF and MCF using water samples taken from Lake Dianchi with severe Microcystis aeruginosa blooms. Removal efficiency, dosage of coagulant/flocculant, rising velocity and structural characteristics of the resulting flocs in the two processes were systematically compared. The results show that CCF could save >50 % polyaluminum chloride (PAC) and polyacrylamide (PAM) compared with MCF when the removal efficiency was both over 95 %. The average rising velocity of flocs in CCF could reach 254.3 m·h-1, much higher than that in MCF (154.5 m·h-1). In the respective optimal coagulation conditions, the flocs formed in CCF (G = 164.8 s-1) were larger (1843 ± 128 µm) and more spherical with a higher fractal dimension (Df = 1.85 ± 0.01) than those generated in MCF (G = 34.1 s-1). The Stokes's Law was found to correctly predict the rising velocity of spherical flocs with large fractal dimensions (Df > 1.7). In contrast, the Haarhoff and Edzwald's extended equation was more suitable for calculating the rising velocity of irregular flocs with small fractal dimension. This study provides new insights into the mechanisms of the enhanced algal removal by CCF and lays foundation for developing cost-efficient algal mitigation processes.