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BACKGROUND: The Mediterranean diet (MD) has shown promising results in preventing type 2 diabetes, particularly in Mediterranean and European populations. However, the applicability of these benefits to non-Mediterranean populations is unclear, with contradictory findings in the literature. METHODS: In this study, we included 12,575 participants without diabetes at baseline from the China Health and Nutrition Survey (CHNS). Dietary intake was measured by three consecutive 24-h dietary recalls. The Mediterranean diet adherence (MDA) was measured by a score scale that included nine components of vegetables, legumes, fruits, nuts, cereals, fish, red meat, dairy products, and alcohol. New-onset diabetes was defined as self-reported physician-diagnosed diabetes during the follow-up. RESULTS: During a median follow-up of 9.0 years, 445 (3.5%) subjects developed diabetes. Overall, there was an inverse association between the MDA score and new-onset diabetes (per score increment, HR 0.83, 95% CI 0.76-0.90). Moreover, age, sex, BMI, and energy intake significantly modified the association between the MDA score and the risk of new-onset diabetes (all P interactions < 0.05). Greater fruit, fish, and nut intake was significantly associated with a lower risk of new-onset diabetes. CONCLUSION: There was an inverse association between Mediterranean diet adherence and new-onset diabetes in the Chinese population.
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Diabetes Mellitus Tipo 2 , Dieta Mediterrânea , Humanos , Dieta Mediterrânea/estatística & dados numéricos , China/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Estudos de Coortes , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Fatores de Risco , Seguimentos , FrutasRESUMO
Initiating aerobic fermentation under low temperature is the main challenge for winter livestock manure composting. This study aims to address this issue by applying black soldier fly larvae (BSFL) frass as a co-composting additive to enhance the low-temperature composting process. Specifically, this work explored the effects of chicken manure and BSFL frass co-composting on the temperature, humus content, and microorganisms with fresh weight ratio of 2:1, 1:1, 1:2 (w/w) at 6 °C. The result showed frass could rapidly rise the temperature to 50 °C and significantly increased the humus content by 15.6 % â¼ 26.3 %. Moreover, microbial analysis revealed that Sphingobacteriaceae accelerated temperature rise via low-temperature reproduction, creating proper temperature for thermophilic bacteria (Truepera and Georgia). Additionally, Cellulomonas and other bacteria promoted organic matter degradation and participated in humus formation. This study presents a novel solution for low-temperature composting, providing practical insights for improving manure management in winter.
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Compostagem , Larva , Esterco , Animais , Compostagem/métodos , Temperatura Baixa , Solo/química , Dípteros/fisiologia , Galinhas , Temperatura , BactériasRESUMO
Nanobubble water promotes the degradation of difficult-to-degrade organic matter, improves the activity of electron transfer systems during anaerobic digestion, and optimizes the composition of anaerobic microbial communities. Therefore, this study proposes the use of nanobubble water to improve the yield of medium chain carboxylic acids produced from cow manure by chain elongation. The experiment was divided into two stages: the first stage involved the acidification of cow manure to produce volatile acidic fatty acids as electron acceptors, and the second phase involved the addition of lactic acid as an electron donor for the chain elongation. Three experimental groups were established, and air, H2, and N2 nanobubble water were added in the second stage. Equal amounts of deionized water were added in the control group. The results showed that nanobubble water supplemented with air significantly increased the caproic acid concentration to 15.10 g/L, which was 55.03 % greater than that of the control group. The relative abundances of Bacillus and Caproiciproducens, which are involved in chain elongation, and Syntrophomonas, which is involved in electron transfer, increased. The unique ability of air nanobubble water supplemented to break down the cellulose matrix resulted in further decomposition of the recalcitrant material in cow manure. This effect subsequently increased the number of microorganisms associated with lignocellulose degradation, increasing carbohydrate metabolism and ATP-binding cassette transporter protein activity and enhancing fatty acid cycling pathways during chain elongation. Ultimately, this approach enabled the efficient production of medium chain carboxylic acids.
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Biodegradação Ambiental , Esterco , Ácidos Carboxílicos/química , Anaerobiose , Animais , Bovinos , Nanoestruturas , Água/química , Ar , Nitrogênio/química , Hidrogênio/química , Transporte de Elétrons , Ácidos Graxos Voláteis/química , ClostridialesRESUMO
Polysaccharides are used in starch-based product formulations to enhance the final quality of food products. This study examined the interaction mechanisms in Ficus pumila polysaccharide (FPP) and wheat starch (WS) gel systems with varying FPP concentrations using linear and nonlinear rheological analysis. Physicochemical structural analyses showed non-covalent FPP-WS interactions, strengthening hydrogen bonding between molecules and promoting water binding and ordered structure generation during WS gel aging. Small amplitude oscillatory shear analyses revealed that elevated FPP concentrations led to increased storage modulus (G'), loss modulus (G"), critical strains (From 29.02 % to 53.32 %) and yield stresses (From 0.94 Pa to 30.97 Pa) in the WS gel system, along with improved resistance to deformation and short-term regeneration. In the nonlinear viscoelastic region, FPP-WS gels shifted from elastic to viscous behavior. Higher FPP concentrations displayed increased energy dissipation, strain hardening (S>0, e3/e1 > 0) and shear thinning (T<0, v3/v1<0). FPP contributes more nonlinearity in the dynamic flow field as showed by the high harmonic ratio, with a larger I3/I1 values overall. This study highlights FPP's potential in starch gel food processing, and offers a theoretical basis for understanding hydrocolloid-starch interactions.
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Ficus , Géis , Polissacarídeos , Reologia , Amido , Triticum , Amido/química , Polissacarídeos/química , Ficus/química , Géis/química , Triticum/química , Viscosidade , Resistência ao CisalhamentoRESUMO
Objective: This study aimed to explore the association between the Chinese visceral adiposity index (CVAI) and cardiometabolic multimorbidity in middle-aged and older Chinese adults. Methods: The data used in this study were obtained from a national cohort, the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018 wave). The CVAI was measured using previously validated biomarker estimation formulas, which included sex, age, body mass index, waist circumference, triglycerides, and high-density lipoprotein cholesterol. The presence of two or more of these cardiometabolic diseases (diabetes, heart disease, and stroke) is considered as cardiometabolic multimorbidity. We used Cox proportional hazard regression models to examine the association between CVAI and cardiometabolic multimorbidity, adjusting for a set of covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to show the strength of the associations. We also conducted a subgroup analysis between age and sex, as well as two sensitivity analyses. Receiver operator characteristic curves (ROC) were used to test the predictive capabilities and cutoff value of the CVAI for cardiometabolic multimorbidity. Results: A total of 9028 participants were included in the final analysis, with a mean age of 59.3 years (standard deviation: 9.3) and women accounting for 53.7% of the sample population. In the fully-adjusted model, compared with participants in the Q1 of CVAI, the Q3 (HR = 2.203, 95% CI = 1.039 - 3.774) and Q4 of CVAI (HR = 3.547, 95% CI = 2.100 - 5.992) were associated with an increased risk of cardiometabolic multimorbidity. There was no evidence of an interaction between the CVAI quartiles and sex or age in association with cardiometabolic multimorbidity (P >0.05). The results of both sensitivity analyses suggested that the association between CVAI and cardiometabolic multimorbidity was robust. In addition, the area under ROC and ideal cutoff value for CVAI prediction of cardiometabolic multimorbidity were 0.685 (95% CI = 0.649-0.722) and 121.388. Conclusion: The CVAI is a valid biomarker with good predictive capability for cardiometabolic multimorbidity and can be used by primary healthcare organizations in the future for early warning, prevention, and intervention with regard to cardiometabolic multimorbidity.
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Adiposidade , Cardiopatias , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Estudos de Coortes , Estudos Longitudinais , Multimorbidade , China/epidemiologia , BiomarcadoresRESUMO
This study reports on the effects of pretreated biogas slurry on degraded farm soil properties, microflora and the production of Capsicum spp. The responses of soil properties, microorganisms and Capsicum spp. production to biogas slurry pretreated soil were determined. The biogas slurry pretreatment of degraded soil increases the total nitrogen (0.15-0.32 g/kg), total phosphorus (0.13-0.75 g/kg), available phosphorus (102.62-190.68 mg/kg), available potassium (78.94-140.31 mg/kg), organic carbon content (0.67-3.32 g/kg) and pH value of the soil, while the population, diversity and distribution of soil bacteria and fungi were significantly affected. Interestingly, soil ammonium nitrogen, soil pH and soil nitrate nitrogen were highly correlated with the population of bacteria and fungi present in the pretreated soil. The soil with biogas slurry pretreatment of 495 m3/hm2 favored the seedling survival rate, flowering rate and fruit-bearing rate of Capsicum spp. and significantly reduced the rate of rigid seedlings. In this study, the application of 495 m3/hm2 biogas slurry to pretreat degraded soil has achieved the multiple goals of biogas slurry valorization, soil biofertilization and preventing and controlling plant diseases caused by soil-borne pathogenic microorganisms. These findings are of significant importance for the safe and environmentally friendly application of biogas slurry for soil pretreatment.
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In recent years, metal-organic frameworks (MOFs) have gained attention in the biomedical field, particularly as drug carriers for treating tumors. Therefore, we decided to synthesize a novel benzoic acid Zn-based MOF and study the Zn-based MOFs' drug-delivery properties and the drug-delivery system's anticancer effects. This study successfully synthesized a zinc-based MOF using solvent thermal synthesis. The crystal structure of a Zn-based MOF was investigated using thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy. Subsequently, the results of UV spectrophotometry showed that Doxorubicin was successfully loaded with a loading amount of 33.74%. Furthermore, the drug release experiments demonstrated that the Zn-based MOF was pH-sensitive, releasing more at a pH of 3.8 than at pH 5.8 or 7.4. Finally, the Zn-based MOF loaded with drugs exhibited high antitumor activity against HepG2 cells while demonstrating remarkably low toxicity to normal cells (LO2). Taken together, these results demonstrate that the Zn-based MOF has the potential to serve as a carrier in the field of drug delivery systems.
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Objective: This prospective study aimed to evaluate the effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies (ADAs) in patients with type 2 diabetes (T2D). Methods: A total of 134 eligible participants were randomly assigned to the test group and the control group. Patients in the test group were treated with beinaglutide and metformin, whereas patients in the control group were randomly treated with aspart 30 and metformin, with a follow-up period of 6 months. The metabolic profiles and ADAs over 6 months were evaluated. Results: After 6 months, 101 (75.37%) patients completed the study. Compared with the control group, the beinaglutide group had significant reductions in 2-h postprandial blood glucose (2hBG) and low blood glucose index (LBGI). Glycated hemoglobin (HbA1c) decreased in both groups relative to baseline. In the test group, one had treatment-emergent beinaglutide ADAs. Significant reductions in triglycerides (TG), non-fasting TG, weight, waist circumference (WC), and body mass index (BMI) were observed. The values of insulin sensitivity index (HOMA-IR) were decreased to a statistically higher degree with beinaglutide treatment. Conclusion: Beinaglutide reduces metabolic dysfunction, LBGI, and weight in patients of T2D with a low risk of ADAs. Beinaglutide may offer the potential for a disease-modifying intervention in cardiovascular disease (CVD). Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200061003.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Glicemia/metabolismo , Estudos Prospectivos , MetabolomaRESUMO
Biogas slurry (BS) is an attractive agricultural waste resource which can be used to regulate soil microbial communities, enhance nutrient absorption capacity of crops, promote plant-soil interactions, and consequently, increase crop productivity. Presently, BS discharge is not environmentally friendly. It is therefore necessary to explore alternative efficient utilization of BS. The use of BS as fertilizer meets the requirements for sustainable and eco-friendly development in agriculture, but this has not been fully actualized. Hence, this paper reviewed the advantages of using BS in farmland as soil fertilization for the improvement of crop production and quality. This review also highlighted the potential of BS for the prevention and control of soil acidification, salinization, as well as improve microbial structure and soil enzyme activity. Moreover, this review reports on the current techniques, application methods, relevant engineering measures, environmental benefits, challenges, and prospects associated with BS utilization. Lastly, additional research efforts require for optimal utilization of BS in farmlands were elucidated.
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ENVISAGE-TAVI AF (Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation; NCT02943785) was a prospective, randomized, open-label trial comparing non-vitamin K oral anticoagulant (NOAC) edoxaban with vitamin K antagonists (VKAs) in patients with atrial fibrillation after successful transcatheter aortic valve replacement (TAVR). The effect of edoxaban- or VKA-based therapy on patient-reported outcomes remains unknown, as most studies focus on efficacy and safety. Pre-TAVR patient-reported expectations and post-TAVR Treatment Satisfaction and Convenience with edoxaban or VKA treatment (at months 3 and 12) were analyzed using the Perception of Anticoagulation Treatment Questionnaire (PACT-Q). This analysis included randomized and dosed patients with an evaluable PACT-Q1 assessment at baseline and ≥1 postbaseline assessment (PACT-Q2). Subanalyses included patients stratified by pre-TAVR anticoagulant (NOAC, VKA, no NOAC/VKA). Edoxaban- (nâ¯=â¯585) and VKA-treated (nâ¯=â¯522) patients had similar baseline characteristics and treatment expectations. Pre-TAVR anticoagulant use did not affect treatment expectations. After TAVR, edoxaban-treated patients had significantly higher Treatment Satisfaction and Convenience scores compared with VKA-treated patients at all time points (p <0.001 for all). Among edoxaban-treated patients, those who received VKAs pre-TAVR were significantly more satisfied with treatment than those who received NOACs (p <0.001) or no NOACs/VKAs (pâ¯=â¯0.003); however, there was no significant difference in the perception of convenience (pâ¯=â¯0.927 and pâ¯=â¯0.092, respectively). Conversely, among VKA-treated patients, the type of anticoagulant used pre-TAVR did not affect Treatment Satisfaction or Convenience scores post-TAVR. In conclusion, patients with atrial fibrillation who received edoxaban post-TAVR reported significantly higher Treatment Satisfaction and Convenience scores compared with those who received VKAs, resulting in a clinically meaningful difference between treatment groups.
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Fibrilação Atrial , Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Humanos , Anticoagulantes , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Administração Oral , Estudos Prospectivos , Satisfação do Paciente , Resultado do Tratamento , Fibrinolíticos/uso terapêutico , Vitamina K , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
Background: Early cardiopulmonary exercise test (CPET) may predict the prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). However, data from CPET to assess the exercise capacity of patients with AMI PCI are still scarce. This study aimed to evaluate the safety of the CPET and assess the predictors and clinical influence of exercise capacity measured by CPET in patients with AMI within 1 week after PCI. Methods: A total of 275 patients with AMI who underwent PCI in the acute phase were selected. Reduced exercise capacity was defined as peak oxygen uptake (VO2peak) <16 mL/kg/min. According to VO2peak, patients were divided into a normal exercise tolerance group and a reduced exercise tolerance group. The general clinical conditions were compared between the 2 groups to investigate the safety of CPET and the influencing factors of exercise tolerance. A nomogram model for predicting patients' exercise capacity was further developed. Clinical outcomes were recorded. Results: The median time of CPET in all patients was 5 days after PCI. Among the 275 patients, exercise tolerance decreased in 90 cases (32.72%). Multivariate logic analysis showed that E/e', age, glycosylated hemoglobin, and estimated glomerular filtration rate (eGFR) were independent predictors of early exercise capacity reduction in these patients. Utilizing the correlation coefficients from pre-assessment clinical and CPET indicators within the logistic regression framework, we constructed a nomogram model to forecast the diminishing exercise tolerance in AMI patients. The predictive accuracy of this model, as indicated by a C-index of 0.771 and an area under the receiver operating characteristic (ROC) curve of 0.771 (95% CI: 0.710-0.832), demonstrates its potential as a robust tool in clinical settings. During a follow-up of 24 months, the incidence of clinical outcomes in patients with low exercise tolerance was significantly higher than that in patients with normal exercise tolerance, among which all-cause mortality and reinfarction were statistically different (P=0.009 and P=0.043). Conclusions: The reduced exercise capacity in patients with AMI after initial PCI is related to age, diastolic dysfunction, renal function, and blood glucose control, which may lead to poor clinical prognosis. The nomogram prediction model performed well in predicting the declining exercise tolerance of patients with AMI.
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BACKGROUND: This prospective study aimed to compare telemedicine-assisted structured self-monitoring of blood glucose(SMBG) with a traditional blood glucose meter (BGM) in adults of type 2 diabetes mellitus (T2DM). METHODS: Adult participants with T2DM were assigned to an intervention group or a control group. The patients in the intervention group received a connected BGM with real-time data submission as well as individual needs-based tele-coaching to address and improve motivation and daily diabetes self-management. The patients in the control group received a traditional BGM. Changes in glycated hemoglobin(HbA1c), low blood glucose index(LBGI), and diabetes self-management behaviors were analyzed. RESULTS: The study demonstrated the superiority of the telemedicine-assisted structured SMBG versus the traditional BGM for improving HbA1c. Additionally, the telemedicine-assisted SMBG reduced the risk of hypoglycemia and enhanced diabetes self-management behaviors, as differences in the LBGI and the Diabetes Self-Management Questionnaire(DSMQ) results between the groups after 6 months were found to be significant. CONCLUSIONS: Telemedicine-assisted structured SMBG helps physicians and patients to achieve a specific level of glycemic control and reduce hypoglycemia. The use of coaching applications and telemedicine-assisted SMBG indicated beneficial effects for T2DM self-management, which may help limit disease progression. TRIAL REGISTRATION: Chinese Clinical Trail Registry No: ChiCTR2300072356 on 12/06/2023. Retrospectively registered.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Telemedicina , Adulto , Humanos , Glicemia , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas , Estudos ProspectivosRESUMO
Objective: Benaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has been approved in the treatment of type 2 diabetes mellitus (T2DM). It is known to lead to significant weight loss, and it is hypothesized that changes in gut microbiota may play a significant role in such weight loss. However, it is unclear how gut microbiota and metabolites change as a result of benaglutide treatment. Methods: Healthy participants and patients with T2DM were included in this study. They received differentiated treatments, and stool specimens were collected separately. These stool specimens were subjected to 16S ribosomal RNA amplicon and metagenomic sequencing to create fecal metabolomic profiles. The diversity of gut microbiota and metabolic products in the stools of each participant was analyzed. Results: The data showed that Faecalibacterium prausnitzii was abundant in the gut microbiota of the control group, which was entirely made up of healthy individuals; however, it showed a statistically significant decrease in patients with T2DM treated with metformin alone, while no significant decrease was observed in patients treated with metformin combined with benaglutide. A metagenomic analysis revealed that benaglutide could improve the fecal microbiota diversity in patients with T2DM. Furthermore, there was a statistically significant correlation between the changes in the metabolites of patients with T2DM and the changes in their gut microbiota (including F. prausnitzii) after treatment with metformin and benaglutide. Conclusion: These findings suggest that the weight-reducing effect of benaglutide is attributed to its ability to normalize the gut microbiota of patients with T2DM, particularly by increasing the abundance of F. prausnitzii.
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Background: Exogenous insulin antibody syndrome (EIAS) is an immunological disorder caused by circulating insulin antibodies (IAs), featuring hypersensitivity to exogenous insulin and insulin resistance. With the wide use of recombinant human insulin and insulin analogs, there has been a significant proliferation of EIAS. Case Report: We describe two cases of diabetes mellitus (DM) with hyperinsulinemia and high serum levels of IAs. They had never been exposed to methimazole, glutathione, lipoic acid, and other sulfhydryl drugs, but they all received insulin treatment. The patient in case 1 had recurrent hypoglycemia before hospitalization. A prolonged oral glucose tolerance test (OGTT) showed hypoglycemia with inappropriately high insulin levels. The patient in case 2 was hospitalized for diabetic ketosis. An OGTT indicated hyperglycemia with hyperinsulinemia and low levels of C-peptide. IAs induced by exogenous insulin in the two patients with DM were positive at high titers, prompting a diagnosis of another condition-EIAS. Conclusion: We discussed the differences between these two cases of EIAS in clinical manifestations and treatment and summarized all patients of EIAS treated in our department to date.
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[This corrects the article DOI: 10.1016/j.heliyon.2023.e15299.].
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Bullying is a problematic public behaviour of great concern worldwide, which occurs commonly in China. Parenting and emotional intelligence have previously been verified as crucial aspects in determining the bullying behaviours of adolescents. However, evidence of the interactive effect of these vital factors needs to be more extensive. This study attempts to analyze the relationships and mechanisms of parenting on bullying through emotional intelligence, which consists of interpersonal and intrapersonal intelligence. Based on Chinese education panel survey data of 8730 adolescents, this paper used OLS regression and SEM methods to estimate the impact and mechanisms of parenting styles on bullying behaviours among adolescents. High-demand and responsive parenting styles can significantly reduce adolescents' bullying behaviours. Intrapersonal and interpersonal intelligence are important mediating variables, and parenting with high demandingness and high responsiveness can significantly improve the interpersonal intelligence of adolescents, thereby reducing children's bullying behaviour. Although low levels of intrapersonal intelligence would increase bullying behaviours in adolescents, high demandingness and high responsiveness of parenting can significantly improve adolescents' intrapersonal intelligence. Parents can reduce adolescents' bullying behaviours by increasing emotional responses and normative requirements. This result provides a new perspective on the solution to the problem of youth bullying.
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The role of plant genotype in determining the assembly of soil microorganisms is widely accepted; however, the effects of cropping with different cultivars of perennial crop plants on the composition of soil microbial communities are not fully understood. In the current study, high-throughput amplicon sequencing and real-time PCR were used to investigate the major features of bacterial community composition, ecological networks, and soil physicochemical properties in three replicate pear orchards, each planted with monocultures of pear cultivars Hosui (HS) or Sucui (SC) of similar ages. A distinct difference in the composition of microbial communities was observed between soils of HS and SC orchards. A significantly greater relative abundance of Verrucomicrobia and Alphaproteobacteria whereas a significantly lower relative abundance of Betaproteobacteria were found in soils of HS cropped orchards than that in SC orchards. Sphingomonas sp., belonging to the Alphaproteobacteria, was recognized as a key species in the co-occurrence network of the microbial interactions. Moreover, redundancy analysis, the Mantel correlation test, and random forest analysis showed that soil pH was the dominant driver in determining microbial community composition in HS soils, whereas soil organic matter was the primary factor determining microbial community composition in SC soils. Altogether, we provide evidence that soils in HS orchards harbor unique microbial communities enriched with respect to microbial groups associated with nutrient cycling, whereas soils in SC orchards are dominated by a group of beneficial microbes exhibiting plant growth promotion. These findings have implications for science-based guidance for manipulation of the soil microbiome to achieve sustainable food production.
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Alphaproteobacteria , Microbiota , Pyrus , Solo/química , Microbiologia do Solo , PlantasRESUMO
Myocardial fibrosis is the most serious complication of viral myocarditis (VMC). This study aimed to investigate the therapeutic benefits and underlying mechanisms of lentivirus-mediated human tissue kallikrein gene transfer in myocardial fibrosis in VMC mice. We established VMC mouse model via intraperitoneal injection with Coxsackie B3 virus. The effect was then assessed after treatment with vehicle, the empty lentiviral vectors (EZ.null), and the vectors expressing hKLK1 (EZ.hKLK1) via tail vein injection for 30 days, respectively. The results showed that administering EZ.hKLK1 successfully induced hKLK1 overexpression in mouse heart. Compared with EZ.null treatment, EZ.hKLK1 administration significantly reduced the heart/weight ratio, improved cardiac function, and ameliorated myocardial inflammation in VMC mice, suggesting that hKLK1 overexpression alleviates VMC in mice. EZ.hKLK1 administration also significantly abrogated the increased myocardial collagen content, type I/III collagen ratio, TGF-ß1 mRNA and protein expression in VMC mice, suggesting that hKLK1 overexpression reduces collagen accumulation and blunts TGF-ß1 signaling in the hearts of VMC mice. In conclusion, our results suggest that hKLK1 alleviates myocardial fibrosis in VMC mice, possibly by downregulating TGF-ß1 expression.
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Cardiomiopatias , Infecções por Coxsackievirus , Miocardite , Camundongos , Humanos , Animais , Miocardite/tratamento farmacológico , Miocardite/metabolismo , Fator de Crescimento Transformador beta1/genética , Colágeno/metabolismo , Colágeno/uso terapêutico , Colágeno Tipo I/genética , Colágeno Tipo I/uso terapêutico , Infecções por Coxsackievirus/terapia , Infecções por Coxsackievirus/tratamento farmacológico , Fibrose , Colágeno Tipo III/uso terapêuticoRESUMO
With global warming, heat stress has become a primary factor that compromises the health and milk quality of dairy cows. Here, we investigated the function and underlying regulatory mechanism of miR-27a-3p in bovine mammary epithelial cells (BMECs) under heat-stress conditions. The current study showed that miR-27a-3p could prevent heat stress-induced BMEC oxidative stress and mitochondrial damage by regulating the balance between mitochondrial fission and fusion processes. Importantly, we found that miR-27a-3p could increase cell proliferation under heat stress conditions by regulating the MEK/ERK pathway and cyclin D1/E1. Interestingly, miR-27a-3p is also involved in the regulation of milk protein synthesis-related protein expression, such as CSN2 and ELF5. Inhibition of the MEK/ERK signaling pathway by AZD6244 blocked the regulatory function of miR-27a-3p in cell proliferation and milk protein synthesis in BMECs under heat stress conditions. Our findings demonstrated that miR-27a-3p protects BMECs from heat stress-induced oxidative stress and mitochondrial damage through the MEK/ERK pathway, thereby promoting BMECs proliferation and lactation in dairy cows. The potential regulatory mechanism of miR-27a-3p in attenuating heat stress-induced apoptosis and lactation defect in BMECs.
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MicroRNAs , Feminino , Animais , Bovinos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas do Leite , Sistema de Sinalização das MAP Quinases , Células Epiteliais/metabolismo , Resposta ao Choque Térmico , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: A spontaneous breathing trial (SBT) is recommended to help patients to liberate themselves from mechanical ventilation as soon as possible in the ICU. The respiratory workload in SBT, which depends on being with or without respiratory support and a specific time, is more accurate to reflect how much support the weaning patients need compared with only considering SBT technologies. AIM: To compare and rank the effectiveness of different respiratory workloads during SBT via differing technologies (Pressure Support Ventilation and T-piece) and differing duration (30 and 120 min) in SBTs. STUDY DESIGN: A comprehensive literature search was performed in six English electronic databases to identify eligible randomized controlled trials (RCTs) published before September 2020. The pooled risk ratio (RR) with 95% confidence interval (CI) was calculated by Markov chain Monte Carlo methods. A Bayesian network meta-analysis was conducted using "gemtc" version 0.8.2 of R software. Each intervention's ranking possibilities were calculated using the surface under the cumulative ranking analysis (SUCRA). RESULTS: A total of nine RCTs including 3115 participants were eligible for this network meta-analysis involving four different commonly used SBT strategies and four outcomes. The only statistically significant difference was between Pressure Support Ventilation (PSV) 30 min and T-piece 120 min in the outcome of the rate of success in SBTs (RR = 0.91; 95% CI, 0.84-0.98). The cumulative rank probability showed that the rate of success in SBT from best to worst was PSV 30 min, PSV 120 min, T-piece 30 min and T-piece 120 min. PSV 30 min and PSV 120 min are more likely to have a higher rate of extubation (SUCRA values of 82.5% for 30 min PSV, 70.7% for 120 min PSV, 36.4% for T-piece 30 min, 10.4% for T-piece 120). Meanwhile, T-piece 120 min (SUCRA, 62.9%) and PSV 120 min (SUCRA, 60.9%) may result in lower reintubation rates, followed by T-piece 30 min (SUCRA, 41.8%) and PSV 30 min (SUCRA, 34.4%). CONCLUSIONS AND RELEVANCE TO CLINICAL PRACTICE: In comprehensive consideration of four outcomes, regarding SBT strategies, 30-min PSV was superior in simple-to-wean patients. Besides, 120-min T-piece and 120-min PSV are more likely to achieve a lower reintubation rate. Thus, the impact of duration is more significant among patients who have a high risk of reintubation. It is still unclear whether the SBTs affect the outcome of mortality; further studies may need to explore the underlying mechanism.