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Enriching microorganisms using a 0.22-µm pore size is a general pretreatment procedure in river microbiome research. However, it remains unclear the extent to which this method loses microbiome information. Here, we conducted a comparative metagenomics-based study on microbiomes with sizes over 0.22 µm (large-sized) and between 0.22 µm and 0.1 µm (small-sized) in a subtropical river. Although the absolute concentration of small-sized microbiome was about two orders of magnitude lower than that of large-sized microbiome, sequencing only large-sized microbiome resulted in a significant loss of microbiome diversity. Specifically, the microbial community was different between two sizes, and 347 genera were only detected in small-sized microbiome. Small-sized microbiome had much more diverse viral community than large-sized fraction. The viruses had abundant ecological functions and were hosted by 825 species of 169 families, including pathogen-related families. Small-sized microbiome had distinct antimicrobial resistance risks from large-sized microbiome, showing an enrichment of eight antibiotic resistance gene (ARG) types as well as the detection of 140 unique ARG subtypes and five enriched risk rank I ARGs. Draft genomes of five major resistant pathogens having diverse ecological and pollutant-degrading functions were only assembled in small-sized microbiome. These findings provide novel insights into river ecosystems, and highlight the overlooked small-sized microbiome in the environment.
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Wastewater treatment plants (WWTPs) are an important source of pharmaceuticals in surface water, but information about their transformation products (TPs) is very limited. Here, we investigated occurrence and transformation of pharmaceuticals and TPs in WWTPs and receiving rivers by using suspect and non-target analysis as well as target analysis. Results showed identification of 113 pharmaceuticals and 399 TPs, including mammalian metabolites (n = 100), environmental microbial degradation products (n = 250), photodegradation products (n = 44) and hydrolysis products (n = 5). The predominant parent pharmaceuticals (n = 37) and transformation products (n = 68) were mainly derived from antimicrobials, accounting for 32.7 % and 17.0 %, respectively. The identified compounds were found in the influent (387-428) and effluent (227-400) of WWTPs, as well as upstream (290-451) and downstream (322-416) of receiving rivers, most predominantly from antimicrobials, followed by analgesic and antipyretic drugs. A total of 399 identified TPs were transformed by 110 pathways, of which the oxidation reaction was predominant (27.0 %), followed by photodegradation reaction (10.7 %). Of the 399 TPs, 49 (with lower PNECs) were predicted to be more toxic than their parents. Compounds with potential high risks (hazard quotient >1 and risk index (RI) > 0.1) were found in the WWTP influent (126), effluent (53) and river (61), and the majority were from the antimicrobial and antihypertensive classes. In particular, the potential risks (RI) of TPs from roxithromycin and irbesartan were found higher than those for their corresponding parents. The findings from this study highlight the need to monitor TPs from pharmaceuticals in the environment.
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Monitoreo del Ambiente , Aprendizaje Automático , Ríos , Aguas Residuales , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Aguas Residuales/química , Preparaciones Farmacéuticas/análisis , Ríos/química , Eliminación de Residuos Líquidos/métodosRESUMEN
BACKGROUND: Green space is an important part of the human living environment, with many epidemiological studies estimating its impact on human health. However, no study has quantitatively assessed the credibility of the existing evidence, impeding their translations into policy decisions and hindering researchers from identifying new research gaps. This overview aims to evaluate and rank such evidence credibility. METHODS: Following the PRISMA guideline, we systematically searched PubMed, Web of Science, and Embase databases for systematic reviews with meta-analyses concerning green spaces and health outcomes published up to January 15, 2024. We categorized the credibility of meta-analytical evidence from interventional studies into four levels (i.e., high, moderate, low, and very low) using the Grading of Recommendation, Assessment, Development and Evaluations framework, based on five domains including risk of bias, inconsistency, indirectness, imprecision, and publication bias. Further, we recalculated all the meta-analyses from observational studies and classified evidence into five levels (i.e., convincing, highly suggestive, suggestive, weak, and non-significant) by considering stringent thresholds for P-values, sample size, robustness, heterogeneity, and testing for biases. FINDINGS: In total, 154 meta-analysed associations (interventional = 44, observational = 110) between green spaces and health outcomes were graded. Among meta-analyses from interventional studies, zero, four (wellbeing, systolic blood pressure, negative affect, and positive affect), 20, and 20 associations between green spaces and health outcomes were graded as high, moderate, low, and very low credibility evidence, respectively. Among meta-analyses from observational studies, one (cardiovascular disease mortality), four (prevalence/incidence of diabetes mellitus, preterm birth, and small for gestational age infant, and all-cause mortality), 12, 22, and 71 associations were categorized as convincing, highly suggestive, suggestive, weak, and non-significant evidence, respectively. INTERPRETATION: The current evidence largely confirms beneficial associations between green spaces and human health. However, only a small subset of these associations can be deemed to have a high or convincing credibility. Hence, future better designed primary studies and meta-analyses are still needed to provide higher quality evidence for informing health promotion strategies. FUNDING: The National Natural Science Foundation of China of China; the Guangzhou Science and Technology Program; the Guangdong Medical Science and Technology Research Fund; the Research Grant Council of the Hong Kong SAR; and Sino-German mobility program.
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Parques Recreativos , Humanos , Metaanálisis como AsuntoRESUMEN
Wastewater treatment plants (WWTPs) serve as the main destination of many wastes containing per- and polyfluoroalkyl substances (PFAS). Here, we investigated the occurrence and transformation of PFAS and their transformation products (TPs) in wastewater treatment systems using high-resolution mass spectrometry-based target, suspect, and non-target screening approaches. The results revealed the presence of 896 PFAS and TPs in aqueous and sludge phases, of which 687 were assigned confidence levels 1-3 (46 PFAS and 641 TPs). Cyp450 metabolism and environmental microbial degradation were found to be the primary metabolic transformation pathways for PFAS within WWTPs. An estimated 52.3 %, 89.5 %, and 13.6 % of TPs were believed to exhibit persistence, bioaccumulation, and toxicity effects, respectively, with a substantial number of TPs posing potential health risks. Notably, the length of the fluorinated carbon chain in PFAS and TPs was likely associated with increased hazard, primarily due to the influence of biodegradability. Ultimately, two high riskcompounds were identified in the effluent, including one PFAS (Perfluorobutane sulfonic acid) and one enzymatically metabolized TP (23-(Perfluorobutyl)tricosanoic acid@BTM0024_cyp450). It is noteworthy that the toxicity of some TPs exceeded that of their parent compounds. The results from this study underscores the importance of PFAS TPs and associated environmental risks.
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Fluorocarburos , Aguas Residuales , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Fluorocarburos/toxicidad , Fluorocarburos/análisis , Fluorocarburos/química , Aguas Residuales/química , Eliminación de Residuos Líquidos , Medición de Riesgo , Aguas del Alcantarillado , Biodegradación AmbientalRESUMEN
Polyurethane is a widely used material because of its excellent properties. Cellulose is a renewable, biocompatible, and biodegradable natural polymer that also has the advantages of a low density, high porosity, and large specific surface area. There are three main types of common nanocellulose: nanocellulose fibers, cellulose nanocrystals, and bacterial nanocellulose. Composites prepared with nanocellulose and polyurethane materials have good mechanical properties and good biocompatibility and can be applied in sensors, 3D printing, self-repairing materials, electromagnetic shielding, and many other areas. This paper details the preparation processes of different nanocelluloses and the application areas of composites, and points to the future development of nanocellulose polyurethane composites.
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BACKGROUND AND AIMS: Engaging in recommended levels of physical activity (PA) is associated with reduced overall and cause-specific mortality rates. Our study aims to examine the relationship between gardening-specific PA and all-cause and cause-specific mortality based on representative U.S. adults. METHODS AND RESULTS: A total of 13,812 adults representing 663.5 million non-institutionalized U.S. adults were included in the National Health and Nutrition Examination Survey. Self-reported gardening activity (GA) was assessed by a validated questionnaire, and outcomes of interest were all-cause mortality and mortality specific to certain causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survey-multivariable Cox proportional hazards models. During a median follow-up period of 16.8 years (Interquartile range = 14.8-18.7), there were 3,476 deaths. After adjusting for potential covariates, we found that participants exposed to GA were more likely to have a lower risk of total mortality [HR (95% CI): 0.76 (0.68, 0.85), P-value < 0.001], cancer-specific mortality [HR (95% CI): 0.81 (0.67, 0.99), P-value < 0.05], cardiovascular disease mortality [HR (95% CI): 0.65 (0.53, 0.80), P-value < 0.001], and respiratory disease mortality [HR (95% CI): 0.66 (0.45, 0.98), P-value < 0.05], compared to those without GA exposure. Furthermore, engaging in GA more frequently and for longer durations was significantly associated with a lower total mortality risk. CONCLUSION: Our study provides evidence that engaging in GA is associated with a decreased risk of overall and cause-specific mortality. However, further longitudinal or interventional studies are needed to investigate the potential benefits of GA.
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Causas de Muerte , Jardinería , Encuestas Nutricionales , Factores Protectores , Conducta de Reducción del Riesgo , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Adulto , Factores de Tiempo , Medición de Riesgo , Anciano , Estilo de Vida SaludableRESUMEN
Social determinants of health (SDoH) have been linked to a higher likelihood of experiencing mental health problems. This study aimed to investigate whether the accumulation of unfavorable SDoH is associated with depression symptom. Data was gathered from a representative population participating in the U.S. National Health and Nutrition Examination Survey spanning from 2005 to 2018. Self-reported SDoH were operationalized according to the criteria outlined in Healthy People 2030, with a cumulative measure of unfavorable SDoH calculated for analysis. The presence of depression symptom was identified using the Patient Health Questionnaire in a representative sample of 30,762 participants (49.2 % males) representing 1,392 million non-institutionalized U.S. adults, with 2,675 (8.7 %) participants showing depression symptom. Unfavorable SDoH were found to be significantly and independently associated with depression symptom. Individuals facing multiple unfavorable SDoHs were more likely to experience depression symptom (P for trend < 0.001). For instance, a positive association was observed in participants exposed to six or more unfavorable SDoHs with depression symptom (AOR = 3.537, 95 % CI: 1.781, 7.075, P-value < 0.001). The findings emphasize that the likelihood of developing depression symptom significantly increases when multiple SDoHs are present, compared to just a single SDoH.
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Depresión , Encuestas Nutricionales , Determinantes Sociales de la Salud , Humanos , Masculino , Femenino , Adulto , Estados Unidos/epidemiología , Depresión/epidemiología , Persona de Mediana Edad , Estudios Transversales , Determinantes Sociales de la Salud/estadística & datos numéricos , Adulto Joven , Anciano , Factores Socioeconómicos , AdolescenteRESUMEN
Combining immune checkpoint blockade with chemotherapy through nanotechnology is promising in terms of safety and efficacy. However, the distinct subcellular distribution of each ingredient's action site makes it challenging to acquire an optimal synergism. Herein, a dual-pH responsive hybrid polymeric micelle system, HNP(αPDL16.9, Dox5.3), is constructed as a proof-of-concept for the spatial cooperativity in chemo-immunotherapy. HNP retains the inherent pH-transition of each polymer, with stepwise disassembly under discrete pH thresholds. Within weakly acidic extracellular tumor environment, αPDL1 is first released to block the checkpoint on cell membranes. The remaining intact Doxorubicin-loaded micelle NP(Dox)5.3 displays significant tropism toward tumor cells and releases Dox upon lysosomal pH for efficient tumor immunogenic cell death without immune toxicity. This sequential-released pattern boosts DC activation and primes CD8+ T cells, leading to enhanced therapeutic performance than single agent or an inverse-ordered combination in multiple murine tumor models. Using HNP, the indispensable role of conventional type 1 DC (cDC1) is identified in chemo-immunotherapy. A co-signature of cDC1 and CD8 correlates with cancer patient survival after neoadjuvant Pembrolizumab plus chemotherapy in clinic. This study highlights spatial cooperativity of chemo- and immuno-agents in immunoregulation and provides insights into the rational design of drug combination for future nanotherapeutics development.
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Doxorrubicina , Inmunoterapia , Micelas , Animales , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Ratones , Concentración de Iones de Hidrógeno , Humanos , Línea Celular Tumoral , Polímeros/química , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Células Dendríticas/metabolismo , Células Dendríticas/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Neoplasias/tratamiento farmacológico , Liberación de FármacosRESUMEN
Textile industry uses varieties of chemicals including per- and polyfluoroalkyl substances (PFAS). PFAS are known to be persistent and incompletely removed in wastewater treatment plants (WWTPs). So far, little is known about what types of PFAS are used in the textile industry and their potential risks. Here we investigated PFAS in two WWTPs and a receiving river of a textile industrial park in Guangxi, China, by using both target and non-target analyses over a two-year period. The target analysis identified 11 specific PFAS, while the non-target analysis revealed a list of 648 different PFAS, including both legacy and emerging substances. Notably, perfluorooctanoic acid (PFOA) was still the most prevalent compound detected. Of particular concern was the finding that the investigated WWTPs, which employs an A/O (Anaerobic/Aerobic) process, exhibited a poor removal efficiency for PFAS. The average removal rate was only 22.0 %, indicating that the current treatment processes are inadequate in effectively mitigating PFAS contamination. Correlation analysis further highlighted the potential for PFAS to be transported from WWTPs to the receiving river, revealing a significant and strong positive correlation between the PFAS in the WWTP effluent and those of the river. Perfluorooctanesulfonic acid (PFOS) and two emerging PFAS (DTXSID30240816 and DTXSID90240817) were identified to have high ecological risks in the receiving river. Notably, these two emerging PFAS are homologues, and their presence in WWTPs has been poorly reported. The findings highlight the wide use and persistence of PFAS in current textile WWTPs, indicating potential long term risks to the receiving environment.
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The contamination characteristics, migration patterns and health risks of per- and polyfluoroalkyl substances (PFAS) were investigated in 66 Chinese paper products by using target and non-target screening methods. Among 57 target PFASs, 5 and 6 PFASs were found in the hygiene paper products (Asunto(s)
Ácidos Alcanesulfónicos
, Fluorocarburos
, Humanos
, Fluorocarburos/análisis
, Etanol
, Alimentos
, Inocuidad de los Alimentos
, China
, Ácidos Alcanesulfónicos/análisis
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To understand the contamination characteristics and ecological risk of antibiotics in contaminated fields of pharmaceutical plantsï¼ samples of the surface soilï¼ soil columnï¼ wastewater treatment process waterï¼ ground waterï¼ and residue dregs were collected from two typical antibiotic pharmaceutical plants in South and North China. A total of 87 commonly used antibiotics were quantified using ultrasound extraction-solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry. The results showed that a total of 31 antibiotics of five classes were detected in all types of samplesï¼ and the maximum concentrations at each sampling point in the surface soilï¼ soil columnï¼ residue dregsï¼ wastewater treatment process waterï¼ and groundwater were 420 ng·g-1ï¼ 595 ng·g-1ï¼ 139 ng·g-1ï¼ 1 151 ng·L-1ï¼ and 6.65 ng·L-1ï¼ respectively. Most of the antibiotics were found in the surface soilï¼ showing a decreasing trend with the depth of the soil column. The ecological risk assessment indicated that sulfamethazineï¼ sulfaquinoxalineï¼ tetracyclineï¼ chlorotetracyclineï¼ and D-sorbitol were at higher risk. Improving the efficiency of antibiotic removal from pharmaceutical wastewater and preventing production shop leaks are effective measures of controlling antibiotic contamination into and around fields in pharmaceutical plants.
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Antibacterianos , Contaminantes Químicos del Agua , Antibacterianos/análisis , Contaminantes Químicos del Agua/análisis , Aguas Residuales , Agua/análisis , China , Suelo , Preparaciones FarmacéuticasRESUMEN
Psychotropic medications are one of the most prescribed pharmaceuticals in the world. Given their frequent detection and ecotoxicity to the no-target organism, the emission of these medications into environments has gradually draw attention. The study developed a sensitive and reliable analytic method to simultaneously investigate 47 psychotropic medications in four matrices: wastewater, surface water, activated sludge, and sediment by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). These 47 target analytes include 24 antidepressants, 17 antianxiety drugs, 5 anticonvulsants, and 1 relevant hormone. Solid phase extraction (SPE) was employed to extract analytes from water-phase samples. Ultrasonic Solvent Extraction method with Enhanced Matrix Removal clean-up (USE-EMR) was utilized to extract target compounds from solid-phase samples, which requires more straightforward and convenient procedures than previous methods. The extraction recoveries of all analytes ranged from 80 % to 120 % in these four sample matrices. In this study, The limit of quantitation for 47 psychotropic medications were 0.15 ng/L (estazolam) to 2.27 ng/L (lorazepam), 0.08 ng/L (desvenlafaxine) to 2 ng/L (mianserin), 0.22 ng/g (dry weight, dw) (nordiazepam) to 3.65 ng/g (dw) (lorazepam), and 0.07 ng/g (dw) (carbamazepine) to 2.85 ng/g (lorazepam), in wastewater, surface water, sludge, and sediment, respectively. In addition, the developed method was employed to analyse actual samples in two wastewater treatment plants and their receiving rivers. Carbamazepine, escitalopram, clozapine, desvenlafaxine, diazepam, lamotrigine, sertraline, temazepam, and venlafaxine were nearly ubiquitous in all matrices. Moreover, this study indicated that the inadequate removal efficiencies of psychotropic medications in wastewater treatment plants (WWTPs) had resulted in a persistent discharge of these contaminants from human sources into environments.
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Espectrometría de Masas en Tándem , Contaminantes Químicos del Agua , Humanos , Espectrometría de Masas en Tándem/métodos , Aguas Residuales , Cromatografía Liquida/métodos , Aguas del Alcantarillado/química , Cromatografía Líquida con Espectrometría de Masas , Lorazepam/análisis , Succinato de Desvenlafaxina/análisis , Agua/análisis , Psicotrópicos/análisis , Extracción en Fase Sólida/métodos , Contaminantes Químicos del Agua/análisis , Carbamazepina/análisis , Cromatografía Líquida de Alta Presión/métodosRESUMEN
AIM: To examine the impact of both individual and cumulative social determinants of health (SDoH) on the likelihood of developing periodontitis, while also exploring any gender disparities in this relationship. MATERIALS AND METHODS: Data of self-reported SDoH domains and sub-items based on Healthy People 2030 were obtained from the U.S. National Health and Nutrition Examination Surveys between 1999 and 2014. Logistic regression models, weighted by survey responses, were used to examine the relationship between SDoH (including eight sub-items and the cumulative number of unfavourable SDoH) and periodontitis. The results were further analysed by gender. RESULTS: A total of 18,075 participants (8867 males and 9208 females) were included in the main analysis, of which 5814 (32.2%) had periodontitis. The study found that certain unfavourable SDoH were individually associated with higher odds of periodontitis, and the cumulative number of unfavourable SDoH was positively linked to the odds of developing periodontitis. Furthermore, males exposed to more unfavourable SDoH appeared to be more susceptible to developing periodontitis than females. CONCLUSIONS: The findings suggest that unfavourable SDoH, especially when they accumulate, are associated with an increased odds of periodontitis and contribute to gender disparities within the U.S.
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Periodontitis , Determinantes Sociales de la Salud , Femenino , Masculino , Humanos , Encuestas Nutricionales , Estudios Transversales , Modelos Logísticos , Periodontitis/epidemiologíaRESUMEN
Neuroinflammation plays a crucial role in the pathogenesis and progression of Alzheimer's disease (AD). The Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) has been shown to promote axonal degeneration and is involved in neuroinflammation. However, the role of SARM1 in AD remains unclear. In this study, we found that SARM1 was reduced in hippocampal neurons of AD model mice. Interestingly, conditional knockout (CKO) of SARM1 in the central nervous system (CNS, SARM1Nestin-CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the Aß deposition and inflammatory infiltration in the hippocampus and inhibited neurodegeneration in APP/PS1 AD model mice. Further investigation into the underlying mechanisms revealed that the signaling of tumor necrosis factor-α (TNF-α) was downregulated in the hippocampus tissues of APP/PS1;SARM1Nestin-CKO mice, thereby alleviating the cognitive decline, Aß deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-α pathway in AD model mice.
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Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/genética , Nestina , Ratones Transgénicos , Factor de Necrosis Tumoral alfa , Enfermedades Neuroinflamatorias , Trastornos de la Memoria/genética , Proteínas del Citoesqueleto/genética , Proteínas del Dominio Armadillo/genéticaRESUMEN
Existing studies have been limited in providing nationally representative data on the relationship between sexual orientation and suicidal ideation (SI) among adults in the U.S. particularly in terms of gender and racial differences. To fill this research gap, we conducted a study using data from the NHANES conducted between 2005 and 2016. Survey-weighted logistic regression models were used to investigate the relationship between sexual orientation and SI risk. Additionally, we performed further analysis by stratifying the data based on demographic variables and performed sensitivity analysis to ensure the reliability of our findings. This study included a weighted sample of 16,564 adults, representing a noninstitutionalized U.S population of 840.1 million. The overall age-adjusted prevalence of SI was found to be 3.5 %. After adjusting for relevant covariates, the study revealed that individuals who identified as something else, homosexual, and bisexual had a higher prevalence risk of suicidal ideation (SI) compared to heterosexual participants. Additionally, the study found that heterosexual participants were 74.4 % less likely to experience SI compared to bisexual individuals. These findings highlight the urgent requirement for inclusive and supportive prevention strategies to effectively address SI among adult sexual minorities in the U.S.
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Conducta Sexual , Ideación Suicida , Adulto , Humanos , Femenino , Masculino , Encuestas Nutricionales , Prevalencia , Reproducibilidad de los ResultadosRESUMEN
THE ETHNOPHARMACOLOGICAL SIGNIFICANCE: Diabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.) DC. (GD), a traditional Chinese herbal medicine with hypoglycemic effects, has been proposed as a potential therapeutic agent for diabetic wound healing. However, the underlying mechanisms of its effects remain unclear. AIM OF THE STUDY: In this study, we aimed to reveal the effect and potential mechanisms of GD on accelerating diabetic wound healing in vitro and in vivo. MATERIALS AND METHODS: The effects of GD on cell proliferation, apoptosis, reactive oxygen species (ROS) production, migration, mitochondrial membrane potential (MMP), and potential molecular mechanisms were investigated in high glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) using CCK-8, flow cytometry assay, wound healing assay, immunofluorescence, DCFH-DA staining, JC-1 staining, and Western blot. Full-thickness skin defects were created in STZ-induced diabetic rats, and wound healing rate was tracked by photographing them every day. HE staining, immunohistochemistry, and Western blot were employed to investigate the effect and molecular mechanism of GD on wound healing in diabetic rats. RESULTS: GD significantly improved HUVEC survival, decreased apoptosis, lowered ROS production, restored MMP, improved migration ability, and raised VEGF expression. The use of Nrf2-siRNA completely abrogated these effects. Topical application of GD promoted angiogenesis and granulation tissue growth, resulting in faster healing of diabetic wounds. The expression of VEGF, CD31, and VEGFR was elevated in the skin tissue of diabetic rats after GD treatment, which upregulated HO-1, NQO-1, and Bcl-2 expression while downregulating Bax expression via activation of the Nrf2 signaling pathway. CONCLUSION: The findings of this study indicate that GD has the potential to serve as a viable alternative treatment for diabetic wounds. This potential arises from its ability to mitigate the negative effects of oxidative stress on angiogenesis, which is regulated by the Nrf2 signaling pathway. The results of our study offer valuable insights into the therapeutic efficacy of GD in the treatment of diabetic wounds, emphasizing the significance of directing interventions towards the Nrf2 signaling pathway to mitigate oxidative stress and facilitate the process of angiogenesis.
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Diabetes Mellitus Experimental , Pie Diabético , Ratas , Humanos , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas , Células Endoteliales de la Vena Umbilical Humana , Transducción de SeñalRESUMEN
Swine farms contaminated the surrounding environment through manure application and biogas slurry irrigation, hence causing the wide residual of multiple antimicrobial drugs (ADs) and their transformation products (TPs). This study performed target, suspect, and nontarget screening methods to comprehensively investigate the pollution profiles of ADs in a typical swine farm, and characterize the potential transformed pathway of TPs and distinguish specific reactions of different catalog of ADs. Samples of fresh feces, compost, biogas slurry, topsoil, column soil, groundwater and plants were analyzed using the database containing 98 target analytes, 679 suspected parent ADs, and â¼ 107 TPs. In total, 29 ADs were quantitively detected, and tetracyclines (TCs) were mostly frequently detected ADs with the concentrations up to 4251 ng/g in topsoil. Soil column investigation revealed that doxycycline (DOX) and tetracycline (TC) in soil could migrate to depths of approximately 1 m in soil. Suspect screening identified 75 parent ADs, with 10 being reported for the first time in environmental media. Semi-quantification of ADs revealed that one of the less-concerned ADs, clinafloxacin, was detected to exceed 5000 ng/L in biogas slurry, suggesting that significant attentions should be paid to these less-concerned ADs. Moreover, 314 TPs was identified, and most of them were found to undergo microbial/enzymatic metabolism pathways. Overall, our study displays a comprehensive overview of ADs and their TPs in swine farming environments, and provides an inventory of crucial list that worthy of concern. The results emphasize the need to quantify the levels and distribution of previously overlooked ADs and their TPs in livestock farms.
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Antiinfecciosos , Biocombustibles , Animales , Porcinos , Granjas , Antibacterianos , Estiércol , SueloRESUMEN
Lacking a highly sensitive exposome screening technique is one of the biggest challenges in moving exposomic research forward. Enhanced in-source fragmentation/annotation (EISA) has been developed to facilitate molecular identification in untargeted metabolomics and proteomics. In this work, with a mixture of 50 pesticides at three concentration levels (20, 4, and 0.8 ppb), we investigated the analytical performance of the EISA technique over the well-accepted targeted MS/MS mode (TMM) in the detection and identification of chemicals at low levels using a quadrupole time-of-flight (qTOF) instrument. Compared with the TMM method, the EISA technique can recognize additional 1, 20, and 23 chemicals, respectively, at the three concentration levels (20, 4, and 0.8 ppb, respectively) investigated. At the 0.8 ppb level, intensities of precursor ions and fragments observed using the EISA technique are 30-1,154 and 3-80 times higher, respectively, than those observed at the TMM mode. A higher matched fragment ratio (MFR) between the EISA technique and the TMM method was recognized for most chemicals. We further developed a chemical annotation informatics algorithm, EISA-EXPOSOME, which can automatically search each precursor ion (m/z) in the MS/MS library against the EISA MS1 spectra. This algorithm then calculated a weighted score to rank the candidate features by comparing the experimental fragment spectra to those in the library. The peak intensity, zigzag index, and retention time prediction model as well as the peak correlation coefficient were further adopted in the algorithm to filter false positives. The performance of EISA-EXPOSOME was demonstrated using a pooled dust extract with a pesticide mixture (n = 200) spiked at 5 ppb. One urine sample spiked with a contaminant mixture (n = 50) at the 5 ppb level was also used for the validation of the pipeline. Proof-of-principal application of EISA-EXPOSOME in the real sample was further evaluated on the pooled dust sample with a modified T3DB database (n = 1650). Our results show that the EISA-EXPOSOME algorithm can remarkably improve the detection and annotation coverage at trace levels beyond the traditional approach as well as facilitate the high throughput screening of suspected chemicals.