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Addressing the global challenge of bacterial resistance demands innovative approaches, among which multitargeting is a widely used strategy. Current strategies of multitargeting, typically achieved through drug combinations or single agents inherently aiming at multiple targets, face challenges such as stringent pharmacokinetic and pharmacodynamic requirements and cytotoxicity concerns. In this report, we propose a bacterial-specific global disruption approach as a vastly expanded multitargeting strategy that effectively disrupts bacterial subcellular organization. This effect is achieved through a pioneering chemical design of ligand-receptor interaction-induced aggregation of small molecules, i.e., DNA-induced aggregation of a diarginine peptidomimetic within bacterial cells. These intracellular aggregates display affinity toward various proteins and thus substantially interfere with essential bacterial functions and rupture bacterial cell membranes in an "inside-out" manner, leading to robust antibacterial activities and suppression of drug resistance. Additionally, biochemical analysis of macromolecule binding affinity, cytoplasmic localization patterns, and bacterial stress responses suggests that this bacterial-specific intracellular aggregation mechanism is fundamentally different from nonselective classic DNA or membrane binding mechanisms. These mechanistic distinctions, along with the peptidomimetic's selective permeation of bacterial membranes, contribute to its favorable biocompatibility and pharmacokinetic properties, enabling its in vivo antimicrobial efficacy in several animal models, including mice-based superficial wound models, subcutaneous abscess models, and septicemia infection models. These results highlight the great promise of ligand-receptor interaction-induced intracellular aggregation in achieving a globally disruptive multitargeting effect, thereby offering potential applications in the treatment of malignant cells, including pathogens, tumor cells, and infected tissues.
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Antibacterianos , Ligantes , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/efeitos dos fármacos , Peptidomiméticos/farmacologia , Peptidomiméticos/química , Separação de FasesRESUMO
The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be "charge-on-backbone" that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.
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Infecções Bacterianas , Peixe-Zebra , Animais , Camundongos , Biofilmes , Bactérias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologiaRESUMO
BACKGROUND: Glyphosate, the herbicide with the highest global usage, has been found to have links to neurological impairment in some occupational studies. Neurofilament light chain (NfL) is a protein that is released into the bloodstream following neuroaxonal damage and has emerged as a reliable biomarker for various neurological disorders. However, no research has investigated the potential link between glyphosate exposure and neurological damage or serum NfL levels in the general population. OBJECTIVE: The objective of this study was to assess the possible correlation between glyphosate exposure and serum NfL levels in a population that is representative of the United States. METHODS: We analyzed data from 597 adults (aged ≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the potential correlation between urinary glyphosate levels and serum NfL levels. RESULTS: We found a significant positive association between urinary glyphosate levels and serum NfL levels (ß-coefficient = 0.110; S.E. = 0.040; P = 0.015), indicating that higher levels of glyphosate exposure may be linked to higher levels of neuroaxonal damage. Furthermore, when glyphosate levels were divided into quintiles, we observed a significant trend of increasing mean NfL concentrations with increasing quintiles of glyphosate exposure (P for trend = 0.036). Notably, the association was more pronounced in certain subgroups, including those aged ≥40 years, non-Hispanic whites, and those with a BMI between 25 and 30. IMPACT STATEMENT: This is the first research to suggest an association between glyphosate exposure and biomarkers indicative of neurological damage in general U.S. adults. If the correlation observed is causal, it raises concerns about the potential effects of glyphosate exposure on neurological health among U.S. adults. The study is noteworthy due to its representation of American adults aged 20 and above, as well as the use of reliable and comprehensive data from the NHANES database.
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Glyphosate, the most widely used herbicide globally, has been linked to neurological impairments in some occupational studies. However, the potential neurotoxic effects of glyphosate exposure in the general population are still not fully understood. We conducted analyses on existing data collected from 1532 adults of the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the possible relationship between glyphosate exposure and cognitive function, depressive symptoms, disability, and neurological medical conditions. Our results showed a significant negative association between urinary glyphosate levels and the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (CERAD-WLT) trial 3 recall and delayed recall scores in both models, with ß coefficients of -0.288 (S.E. = 0.111, P = 0.021) and -0.426 (S.E. = 0.148, P = 0.011), respectively. Furthermore, the odds ratio did not show a significant increase with the severity of depressive symptoms with a one-unit increase in ln-glyphosate levels. However, the odds ratio for severe depressive symptoms was significantly higher than for no symptoms (odds ratio = 4.148 (95% CI = 1.009-17.133), P = 0.049). Notably, the odds ratio showed a significant increase for individuals with serious hearing difficulty (odds ratio = 1.354 (95% CI = 1.018-1.800), P = 0.039) with a one-unit increase in ln-glyphosate levels, but not for other neurological medical conditions. In conclusion, our findings provide the first evidence that glyphosate exposure may be associated with neurological health outcomes in the US adult population. Additional investigation is necessary to understand the potential mechanisms and clinical significance of these correlations.
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Menopausal syndrome (MS) refers to a series of symptoms with autonomic nervous system dysfunction caused by decreased sex hormones before and after menopause. Baihe Dihuang (BHDH) decoction positively affects MS, but its mechanism remains unclear. This study aimed to reveal the underlying mechanism through network pharmacology. The components of the BHDH Decoction were found through HERB, while corresponding targets were obtained from the HERB, Drug Bank, NPASS, Targetnet, and Swisstarget databases. The MS targets were obtained from GeneCards and OMIM. STRING was used to construct the protein-protein interaction networks. OmicShare tools were used for Gene Ontology and Kyoto encyclopedia of genes and genomes analyses. Finally, Autodock Vina 1.1.2 software (https://vina.scripps.edu/downloads/) was used for molecular alignment to verify whether the main active ingredients and key targets had good binding activity. We screened out 27 active ingredients and 251 effective targets of BHDH Decoction, 3405 MS-related targets, and 133 intersection targets between BHDH Decoction and MS. Protein-protein interaction network identified tumor protein P53, Serine/threonine-protein kinase AKT, epidermal growth factor receptor, Estrogen Receptor 1, and jun proto-oncogene as critical targets. Gene ontology analysis showed that these targets were mainly involved in the cellular response to chemical stimulus, response to oxygen-containing compound, cellular response to endogenous stimulus, response to an organic substance, and response to chemical, etc. Kyoto encyclopedia of genes and genomes pathways were mainly enriched in endocrine resistance, pathways in cancer, and the ErbB signaling pathway, etc. Molecular docking results showed that emodin and stigmasterol are strongly associated with Serine/threonine-protein kinase AKT, Estrogen Receptor 1, epidermal growth factor receptor, sarcoma gene, and tumor protein P53. This study preliminarily revealed the multi-component, multi-target, and multi-channel mechanism of BHDH Decoction in treating MS. It provides a reference for in vitro and in vivo research and clinical application of BHDH Decoction in the treatment of MS.
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Medicamentos de Ervas Chinesas , Farmacologia em Rede , Feminino , Humanos , Receptor alfa de Estrogênio , Proteína Supressora de Tumor p53 , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt , Menopausa , Receptores ErbB , Treonina , Serina , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional ChinesaRESUMO
Di (2-ethylhexyl) phthalate (DEHP) is a chemical commonly used in the manufacturing of plastics and can pose human health risks, including endocrine disruption, reproductive toxicity, and potential carcinogenic effects. Children may be particularly vulnerable to the harmful effects of DEHP. Early exposure to DEHP has been linked to potential behavioral and learning problems. However, there are no reports to date on whether DEHP exposure in adulthood has neurotoxic effects. Serum neurofilament light chain (NfL), a protein released into the blood after neuroaxonal damage, has been shown to be a reliable biomarker for many neurological diseases. To date, no study has examined the relationship between DEHP exposure and NfL. For the present study, we selected 619 adults (aged ≥ 20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the association between urinary DEHP metabolites and serum NfL. We reported higher urinary levels of ln-mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), ln-mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and ln-mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and ln-ΣDEHP levels were associated with higher serum levels of ln-NfL (ΣDEHP: ß-coefficient = 0. 075; S.E. = 0.026; P = 0.011). When we divided ΣDEHP into quartiles, mean NfL concentrations increased with quartiles of MEHHP (P for trend = 0.023). The association was more pronounced in males, non-Hispanic white race, higher income, and BMI < 25. In conclusion, higher DEHP exposure was positively associated with higher serum NfL in adults from NHANES 2013-2014. If this finding is causal, it is possible that DEHP exposure in adulthood may also induce neurological damage. Although the causality of this observation and the clinical significance are uncertain, our findings suggest that additional research is needed on DEHP exposure, serum NfL, and neurological disease in adults.
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Dietilexilftalato , Ácidos Ftálicos , Masculino , Criança , Adulto , Humanos , Dietilexilftalato/metabolismo , Inquéritos Nutricionais , Filamentos Intermediários/metabolismo , Ácidos Ftálicos/metabolismo , Biomarcadores/urina , Exposição AmbientalRESUMO
Most Gram-positive-selective antibiotics have low activity against Gram-negative bacteria due to the presence of an outer membrane barrier. There is, therefore, interest in developing combination therapies that can penetrate the outer membrane (OM) with known antibiotics coupled with membrane-active sensitizing adjuvants. However, two unanswered questions hinder the development of such combination therapies: the sensitization spectrum of the sensitizer and the mechanism of antibiotic-sensitizer mutual potentiation. Here, with pentamidine as an example, we screened a library of 170 FDA-approved antibiotics in combination with pentamidine, a compound known to disturb the OM of Gram-negative bacteria. We found that four antibiotics, minocycline, linezolid, valnemulin, and nadifloxacin, displaced enhanced activity in combination with pentamidine against several multidrug-resistant Gram-negative bacteria. Through a descriptor-based structural-activity analysis and multiple cell-based biochemical assays, we found that hydrophobicity, partial charge, rigidity, and surface rugosity were key factors that affected sensitization via a cooperative membrane damage mechanism in which lipopolysaccharides and phospholipids were identified as sites of synergy. Finally, in vitro experiments showed that the linezolid-pentamidine combination slowed the generation of drug resistance, and there was also potent activity in in vivo experiments. Overall, our results highlight the importance of the physicochemical properties of antibiotics and cooperative membrane damage for synergistic pentamidine-antibiotic drug combinations.
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Antibacterianos , Pentamidina , Antibacterianos/farmacologia , Antibacterianos/química , Pentamidina/farmacologia , Linezolida/farmacologia , Bactérias Gram-Negativas , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade MicrobianaRESUMO
Non-alcoholic steatohepatitis (NASH) is affecting people worldwide. Changes in the intestinal microbiome are crucial to NASH. A previous study showed that eradicating intestinal fungi ameliorates NASH; however, the role of intestinal fungi in the development of NASH remains unclear. Saccharomyces boulardii (SB), a dietary supplement yeast, has been reported to restore the integrity of the intestine. Here, we tested the effect of SB in the treatment of NASH. For this study, we fed eight-week-old C57/BL6 male mice either a methionine-choline deficient (MCD) diet or a normal chow diet (NCD) for eight weeks. Half of the MCD diet-fed mice were gavaged with SB (5 mg/day) once daily. The remainder of the NCD-fed mice were gavaged with normal saline as a control. The MCD diet-fed mice on SB supplement showed better liver function, less hepatic steatosis, and decreased inflammation. Both hepatic inflammatory gene expression and fibrogenic gene expression were suppressed in mice with SB gavage. Intestinal damage caused by the MCD diet was tampered with, intestine inflammation decreased, and gut permeability improved in mice that had been given the SB supplement. Deep sequencing of the fecal microbiome showed a potentially increased beneficial gut microbiota and increased microbiota diversity in the SB-supplemented mice. The SB supplement maintains gut integrity, increases microbial diversity, and increases the number of potentially beneficial gut microbiota. Thus, the SB supplement attenuates gut leakage and exerts a protective effect against NASH. Our results provide new insight into the prevention of NASH.
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The understanding of microbial compositions in different dimensions is essential to achieve the successful design and operation of the partial nitritation/anammox (PN/A) process. This study investigated the microbial communities of different sludge morphologies and spatial distribution in the one-stage PN/A process of treating real coal to ethylene glycol (CtEG) wastewater at a pilot-scale integrated fixed-film activated sludge (IFAS) reactor. The results showed that ammonia-oxidizing bacteria (AOB) was mainly distributed in flocs (13.56 ± 3.16%), whereas anammox bacteria (AnAOB) was dominated in the biofilms (17.88 ± 8.05%). Furthermore, the dominant AnAOB genus in biofilms among the first three chambers was Candidatus Brocadia (6.46 ± 2.14% to 11.82 ± 6.33%), whereas it was unexpectedly transformed to Candidatus Kuenenia (9.47 ± 1.70%) and Candidatus Anammoxoglobus (8.56 ± 4.69%) in the last chamber. This demonstrated that the niche differentiation resulting from morphological (dissolved oxygen) and spatial heterogeneity (gradient distribution of nutrients and toxins) was the main reason for dominant bacterial distribution. Overall, this study presents more comprehensive information on the heterogeneous distribution and transformation of communities in PN/A processes, providing a theoretical basis for targeted culture and selection of microbial communities in practical engineering.
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PURPOSE: Di-(2-ethylhexyl) phthalate (DEHP) has been utilized in many daily products for decades. Previous studies have reported that DEHP exposure could induce renin-angiotensin-aldosterone system activation and increase epithelial sodium channel (ENaC) activity, which contributes to extracellular fluid (ECF) volume expansion. However, there is also no previous study to evaluate the association between DEHP exposure and body fluid status. METHODS: We selected 1678 subjects (aged ≥18 years) from a National Health and Nutrition Examination Survey (NHANES) in 2003-2004 to determine the relationship between urine DEHP metabolites and body composition (body measures, bioelectrical impedance analysis (BIA)). RESULTS: After weighing the sampling strategy in multiple linear regression analysis, we report that higher levels of DEHP metabolites are correlated with increases in body measures (body weight, body mass index (BMI), waist circumference), BIA parameters (estimated fat mass, percent body fat, ECF, and ECF/intracellular fluid (ICF) ratio) in multiple linear regression analysis. The relationship between DEHP metabolites and the ECF/ICF ratio was more evident in subjects of younger age (20-39 years old), women, non-Hispanic white ethnicity, and subjects who were not active smokers. CONCLUSION: In addition to being positively correlated with body measures and body fat, we found that urine DEHP metabolites were positively correlated with ECF and the ECF/ICF ratio in the US general adult population. The finding implies that DEHP exposures might increase ECF volume and the ECF/ICF ratio, which may have adverse health outcomes on the cardiovascular system. Further research is needed to clarify the causal relationship.
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Líquidos Corporais , Dietilexilftalato , Ácidos Ftálicos , Adolescente , Adulto , Líquidos Corporais/metabolismo , Dietilexilftalato/urina , Exposição Ambiental/análise , Feminino , Humanos , Inquéritos Nutricionais , Ácidos Ftálicos/urina , Adulto JovemRESUMO
Gram-negative bacteria, especially the ones with multidrug resistance, post dire challenges to antibiotic treatments due to the presence of the outer membrane (OM), which blocks the entry of many antibiotics. Current solutions for such permeability issues, namely lipophilic-cationic derivatization of antibiotics and sensitization with membrane-active agents, cannot effectively potentiate the large, globular, and hydrophilic antibiotics such as vancomycin, due to ineffective disruption of the OM. Here, we present our solution for high-degree OM binding of vancomycin via a hybrid "derivatization-for-sensitization" approach, which features a combination of LPS-targeting lipo-cationic modifications on vancomycin and OM disruption activity from a sensitizing adjuvant. 106- to 107-fold potentiation of vancomycin and 20-fold increase of the sensitizer's effectiveness were achieved with a combination of a vancomycin derivative and its sensitizer. Such potentiation is the result of direct membrane lysis through cooperative membrane binding for the sensitizer-antibiotic complex, which strongly promotes the uptake of vancomycin and adds to the extensive antiresistance effectiveness. The potential of such derivatization-for-sensitization approach was also supported by the combination's potent in vivo antimicrobial efficacy in mouse model studies, and the expanded application of such strategy on other antibiotics and sensitizer structures.
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Bactérias Gram-Negativas , Vancomicina , Animais , Antibacterianos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Vancomicina/farmacologiaRESUMO
The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.
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COVID-19 , Análise Serial de Proteínas , Enzima de Conversão de Angiotensina 2 , Anticorpos Neutralizantes , Humanos , Isotipos de ImunoglobulinasRESUMO
Site-specific modification of proteins has important applications in biological research and drug development. Reactive tags such as azide, alkyne, and tetrazine have been used extensively to achieve the abovementioned goal. However, bulky side-chain "ligation scars" are often left after the labeling and may hinder the biological application of such engineered protein products. Conjugation chemistry via dehydroalanine (Dha) may provide an opportunity for "traceless" ligation because the activated alkene moiety on Dha can then serve as an electrophile to react with radicalophile, thiol/amine nucleophile, and reactive phosphine probe to introduce a minimal linker in the protein post-translational modifications. In this report, we present a mild and highly efficient enzymatic approach to incorporate Dha with phosphothreonine/serine lyases, OspF and SpvC. These lyases originally catalyze an irreversible elimination reaction that converts a doubly phosphorylated substrate with phosphothreonine (pT) or phosphoserine (pS) to dehydrobutyrine (Dhb) or Dha. To generate a simple monophosphorylated tag for these lyases, we conducted a systematic approach to profile the substrate specificity of OspF and SpvC using peptide arrays and self-assembled monolayers for matrix-assisted laser desorption/ionization mass spectrometry. The optimized tag, [F/Y/W]-pT/pS-[F/Y/W] (where [F/Y/W] indicates an aromatic residue), results in a â¼10-fold enhancement of the overall peptide labeling efficiency via Dha chemistry and enables the first demonstration of protein labeling as well as live cell labeling with a minimal ligation linker via enzyme-mediated incorporation of Dha.
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Liases , Alanina/análogos & derivados , Alanina/química , Liases/metabolismo , Fosfotreonina/metabolismo , Processamento de Proteína Pós-Traducional , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Background: Microglia have been identified for a century. In this period, their ontogeny and functions have come to light thanks to the tireless efforts of scientists. However, numerous documents are being produced, making it challenging for scholars, especially those new to the field, to understand them thoroughly. Therefore, having a reliable method for quickly grasping a field is crucial. Methods: We searched and downloaded articles from the Web of Science Core Collection with "microglia" or "microglial" in the title from 2002 to 2021. Eventually, 12,813 articles were located and, using CiteSpace and VOSviewer, the fundamental data, knowledge domains, hot spots, and emerging trends, as well as the influential literature in the field of microglia research, were analyzed. Results: Following 2011, microglia publications grew significantly. The two prominent journals are Glia and J Neuroinflamm. The United States and Germany dominated the microglia study. The primary research institutions are Harvard Univ and Univ Freiburg, and the leading authors are Prinz Marco and Kettenmann Helmut. The knowledge domains of microglia include eight directions, namely neuroinflammation, lipopolysaccharide, aging, neuropathic pain, macrophages, Alzheimer's disease, retina, and apoptosis. Microglial phenotype is the focus of research; while RNA-seq, exosome, and glycolysis are emerging topics, a microglial-specific marker is still a hard stone. We also identified 19 influential articles that contributed to the study of microglial origin (Mildner A 2007; Ginhoux F 2010), identity (Butovsky O 2014), homeostasis (Cardona AE 2006; Elmore MRP 2014); microglial function such as surveillance (Nimmerjahn A 2005), movement (Davalos D 2005; Haynes SE 2006), phagocytosis (Simard AR 2006), and synapse pruning (Wake H 2009; Paolicelli RC 2011; Schafer DP 2012; Parkhurst CN 2013); and microglial state/phenotype associated with disease (Keren-Shaul H 2017), as well as 5 review articles represented by Kettenmann H 2011. Conclusion: Using bibliometrics, we have investigated the fundamental data, knowledge structure, and dynamic evolution of microglia research over the previous 20 years. We hope this study can provide some inspiration and a reference for researchers studying microglia in neuroscience.
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BACKGROUND: Craniopharyngioma (CP) is a challenging intracranial tumor due to its special hypothalamus-pituitary location. Each patient with CP should be evaluated and treated separately. Exploring novel methods of automatized analysis of data for gaining knowledge on any medical field is an encouraging task, particularly in such an extremely challenging tumor as CP. We aim to summary the situations, investigate the research trends and evaluate research hotspots using bibliometric analysis for the CP research. METHODS: We extracted all the CP-related literatures from 2011 to 2020 from the Web of Science database. An Online analysis platform of literature metrology (Bibliometric), BICOMB, gCLUTO and CiteSpace softwares were used to do bibliometric analysis. As a supplement, we also analyzed the top 100 cited case reports with particular and certainly infrequent information to improve the analysis. RESULTS: According to our retrieval strategy, we found a total of 1262 CP-related literatures. The United States has maintained a leading position in global CP research, followed by China and Germany. Among institutions, Capital Med Univ, St Jude Childrens Res Hosp and Southern Med Univ rank in the top 3 in terms of the number of articles published. "WORLD NEUROSURGERY" is the most popular journal for CP-related research. Moreover, MULLER HL, MERCHANT TE, QI ST and others have made great achievements in the study of CP. Finally, we did biclustering analysis on keywords and identified 4 CP research hotspot clusters. CONCLUSIONS: Our research provides a comprehensive analysis of the scientific progress of CP in the past 10 years, and insight into the development of CP research field, highlight research trends over time, and help identify valuable future directions.
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PURPOSE: Previous reports have identified the important role of zinc in bone health. Although the risk of zinc deficiency is still a concern in the U.S., there has never been an in-depth study of the association between zinc status and bone health in a sample representing the country. METHODS: We included 2,895 subjects (aged ≥ 40 years) from National Health and Nutrition Examination Survey (NHANES) 2013-2014 to explore the relationship among three biomarkers of zinc (serum, food, and total intake), the bone mineral density (BMD) of the total spine and femur, the FRAX® scores, and the previous history of bone fractures. RESULTS: We showed a one-unit increase in the ln-serum zinc level was associated with an increase in the total spine BMD (ß = 0.068; S.E. = 0.028; P = 0.030) and total femur BMD (ß = 0.061; S.E. = 0.017; P = 0.003), while a one-unit increase in the ln-food zinc intake amount was correlated with an increase in the total femur BMD in the participants (ß = 0.023; S.E. = 0.009; P = 0.021). The ln-total zinc intake amount was correlated with an increase in the total femur BMD in women (ß = 0.016; S.E. = 0.007; P = 0.041). We also found food zinc intake was negatively correlated with the FRAX® score, while increased levels of all three zinc biomarkers were associated with a decreased incidence of previous bone fractures. CONCLUSIONS: In this representative survey of American adults above 40 years old, higher zinc status was associated with higher total spine and femoral BMD, lower FRAX® scores, and lower incidence of previous fractures. If this finding is causal, increased zinc intake remains an important issue for Americans.
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Densidade Óssea , Absorciometria de Fóton , Adulto , Feminino , Humanos , Inquéritos Nutricionais , Fraturas por Osteoporose , Medição de Risco , ZincoRESUMO
Selenium is an essential trace mineral element for humans. Although previous in vitro and animal studies have reported the vital role of selenium in bone, the results of the relationship between the selenium status and bone health were inconsistent in epidemiological studies. The risk of selenium deficiency is negligible for U.S. general population, however, the relationship between selenium status and bone health has never been surveyed in a nationally representative sample. In this study, we analyzed the data of 2983 adults (aged ≥40 years) in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to investigate the association among three markers of the selenium status (measured from whole blood, serum, and dietary intake), total spine and femur bone mineral density (BMD), and FRAX scores, and history of bone fractures. We found a one-unit increase in the ln-whole-blood selenium level was correlated with an increase in the total femur BMD of 0.064 g/cm2 (S.E. = 0.025; P = 0.022) in all participants and 0.086 g/cm2 (S.E. = 0.031; P = 0.013) in menopausal women. Additionally, a one-unit increase in the ln-selenium intake amount was associated with an increase in the total femur BMD of 0.014 g/cm2 (S.E. = 0.007; P = 0.043) in all participants. We also found that the dietary and whole-blood selenium statuses were negatively associated with the FRAX score, while levels of all the three selenium biomarkers were negatively associated with a history of bone fractures. In conclusion, increased selenium status is correlated with an increased total femur BMD, decreased FRAX scores, and a reduced incidence of previous bone fractures in the U.S. representative survey of adults. Further study is warranted to clarify the causal inference.
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Fraturas Ósseas , Fraturas por Osteoporose , Selênio , Absorciometria de Fóton , Adulto , Densidade Óssea , Feminino , Fêmur , Humanos , Inquéritos Nutricionais , Medição de RiscoRESUMO
In this study, a novel process was developed to treat real sewage with a low chemical oxygen demand/total nitrogen ratio (COD/TN = 3.2) and to obtain enhanced nitrogen removal through Anaerobic ammonia oxidation (anammox). Anaerobic/aerobic/anoxic/aerobic (AOAO) reactor processes were amended with a fixed anammox biofilm in the anoxic zone. During an operational period of 212 days, an average effluent TN of 13.7 mg/L with a removal efficiency of 72.0% was obtained with an influent of 47.0 mg/L ammonium. Mass balance analysis suggested that the anammox resulted in removal of 33.6% of the TN. Besides, by adding sludge fermentation products, nitrite accumulation occurred via nitration while in the aerobic zone for the anammox process. This study demonstrated an alternative way to apply a sewage anammox process via excess sludge fermentation products triggering nitrite production in a continuous flow reactor.
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Esgotos , Águas Residuárias , Reatores Biológicos , Desnitrificação , Fermentação , Nitrogênio , OxirreduçãoRESUMO
This study investigated the inhibitory effect of free nitrous acid (FNA) on the activity of ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) under anoxic conditions with different mixed liquid suspended solids (MLSS). Sequencing batch reactors were used to study the changes in the activity of AOB and NOB in nitrifying activated sludge based on four different MLSS (8398, 11254, 15998, and 19637 mg·L-1), after treatment, under anoxic conditions with FNA (at an initial concentration of 1.3 mg·L-1) for 48 h. The results showed that the pH increased by approximately 0.9, but the concentration of NO2--N did not decrease significantly. With over-aeration, the concentration of NH4+-N gradually degraded to 0 mg·L-1, and the removal rate of NH4+-N gradually increased to a maximum of 4.4-6.8 mg·(L·h)-1 which time used was shorter with the increase of the inhibition MLSS. The nitrite accumulation rate was more than 92% when the sludge concentration was 8398, 11254, 15998, and 19637 mg·L-1 and with over-aeration for 0-396 h, 0-396 h, 0-372 h, and 0-168 h, respectively. When aerated for 468 h, 468 h, 444 h, and 264 h, the NO2--N concentration and NAR decreased to 0, and NO3--N concentrations increased to their highest with the values of 42.6, 49.9, 42.9, and 47.9 mg·L-1 respectively.
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Bactérias/metabolismo , Nitritos/análise , Ácido Nitroso/química , Esgotos/microbiologia , Amônia/análise , Reatores Biológicos/microbiologia , NitrificaçãoRESUMO
Various 1,3,4-oxadiazole thioether derivatives containing 2-chloro-5-methylene pyridine, 2-chloro-5-methylene thiazole, 3,4-dimethoxy-2-methylene pyridine, and N,N-dimethyl-2-ethylamino moieties were designed, synthesized, and assessed for their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) via the turbidimeter test in vitro. Preliminary bioassay results confirmed good antibacterial activities for most of these compounds. Among these substances, compound 6r showed the best inhibitory effect against Xoo, and its half-maximal effective concentration (EC50) value is 4.78µg/mL, which is superior to that of commercial agent bismerthiazol (87.55µg/mL). We then performed a label-free quantitative proteomic analysis of the response of Xoo to 6r. A total of 1363 proteins were identified in the control and treatment groups. Upon treatment with the minimum inhibitory concentration, 349 proteins were found to be differentially expressed (fold changes>1.5, p<0.05), enriched, and may be involved in purine metabolism.