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1.
Immun Inflamm Dis ; 12(4): e1211, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38602270

RESUMO

BACKGROUND: Traumatic cartilage injury is an important cause of osteoarthritis (OA) and limb disability, and toll-like receptors (TLRs) mediated innate immune response has been confirmed to play a crucial role in cartilage injury. In the previous study, we found that the activation of TLR8 molecules in injured articular cartilage was more obvious than other TLRs by establishing an animal model of knee impact injury in rabbits, and the changes of TLR8 molecules could significantly affect the process of articular cartilage injury and repair. OBJECTIVE: To verify how mir-99a-5p regulates TLR8 receptor mediated innate immune response to treat traumatic cartilage injury. METHODS: The impact of a heavy object on the medial condyle of the rabbit's knee joint caused damage to the medial condylar cartilage. Through pathological and imaging analysis, it was demonstrated whether the establishment of an animal model of traumatic cartilage injury was successful. Establishing a cell model by virus transfection of chondrocytes to demonstrate the role of TLR8 in the innate immune response to impact cartilage injury. Through transcriptome sequencing, potential targets of TLR8, mir-99a-5p, were predicted, and basic experiments were conducted to demonstrate how they interact with innate immune responses to impact cartilage damage. RESULTS: TLR8 is a receptor protein of the immune system, which is widely expressed in immune cells. In our study, we found that TLR8 expression is localized in lysosomes and endosomes. Mir-99a-5p can negatively regulate TLR8 to activate PI3K-AKT molecular pathway and aggravate cartilage damage. Inhibiting TLR8 expression can effectively reduce the incidence of articular cartilage damage. CONCLUSION: Based on the results from this study, mir-99a-5p may be an effective molecular marker for predicting traumatic cartilage injury and targeting TLR8 is a novel and promising approach for the prevention or early treatment of cartilage damage.


Assuntos
Cartilagem Articular , MicroRNAs , Animais , Coelhos , MicroRNAs/genética , Receptor 8 Toll-Like/metabolismo , Fosfatidilinositol 3-Quinases , Articulação do Joelho/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia
2.
Adv Sci (Weinh) ; 11(16): e2306915, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38357830

RESUMO

Recent studies suggest that circular RNA (circRNA)-mediated post-translational modification of RNA-binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi-omics approach. Has_circ_0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif-containing 21 to reduce the proteasome-mediated degradation of NCL via K48-linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient-derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi-omics landscape of circRNA-mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Circular , Ubiquitinação , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Ubiquitinação/genética , Camundongos , Animais , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Linhagem Celular Tumoral , 60657 , Metástase Neoplásica/genética , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Modelos Animais de Doenças , Multiômica
3.
J Zhejiang Univ Sci B ; 25(1): 83-90, 2024 Jan 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38163668

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Sarcopenia , Humanos , Idoso , Sarcopenia/diagnóstico , Sarcopenia/diagnóstico por imagem , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Prognóstico , 60570 , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Retrospectivos
4.
Plant Physiol Biochem ; 206: 108279, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128226

RESUMO

Polygonum multiflorum Thunb. is a traditional Chinese medicine with extensive distribution and robust adaptability, but comprehensive research on its acid and alkali resistance is presently lacking. This study aimed to analyze the effects of 5 months of continuous pH stress on the physiological and photosynthetic parameters of P. multiflorum, and the content of effective components. Results revealed that pH stress significantly influenced the normal growth, physiological functions, and photosynthetic indicators of P. multiflorum. At soil pH 4.5, the tubers of P. multiflorum exhibited the highest levels of 2,3,5,4'-tetrahydroxy stilbene-2-O-ß-d-glucoside (THSG) and total anthraquinones at 5.41% and 0.38%, respectively. However, increased soil pH significantly reduced the content of THSG and total anthraquinones. Reference-free transcriptome analysis was further conducted on P. multiflorum treated at pH 4.5 and 9.5, generating a total of 47,305 unigenes with an N50 of 2118 bp, of which 31,058 (65.65%) were annotated. Additionally, 2472 differentially expressed genes (DEGs) were identified. Among them, 17 DEGs associated with the biosynthesis of THSG and anthraquinones were screened. A comprehensive analysis of differential gene expression and effective component content demonstrated a significant positive correlation between the content of effective components and the 14 DEGs' expression but a negative correlation with soil pH. This study highlighted the influence of varying soil pH values on the effective component content of P. multiflorum. Specific acidic conditions proved beneficial for the synthesis and accumulation of THSG and total anthraquinones in P. multiflorum, thereby enhancing the quality of the medicinal material.


Assuntos
Fallopia multiflora , Estilbenos , Fallopia multiflora/genética , Fallopia multiflora/química , Antraquinonas/análise , Tubérculos/química , Solo , Concentração de Íons de Hidrogênio
5.
PLoS One ; 18(12): e0294610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38055676

RESUMO

The COVID-19 epidemic had an appropriate impact on tourists' trip psychology and their subsequent behavior in participating in rural tourism activities. The purpose of this paper is to explore the types of motivations Chinese tourists have for participating in rural tourism in the context of COVID-19, and to comparatively analyze the similarities and differences in motivations for rural tourism during the epidemic and in normal times. An interpretive paradigm qualitative data collection method was used: semi-structured interviews and focus group discussions. Respondents were 21 tourists, who were selected through purposive and snowball sampling. Through content analysis, we found that rural tourism motivations during the epidemic included both diversified and singular motivations. The pull effect of rural destinations is related to distance and ease of realization. For rural areas in close proximity, a single motivation is sufficient to drive tourists. In addition, we found that there was no "altruistic motivation" for rural tourism during the COVID-19 period, but "altruistic feelings" for the preservation of ancient villages were generated during rural tourism. Finally, we discuss the theoretical and practical significance of this study and make suggestions for future research. The study explains tourists' companionship preferences, activity choices, and affective changes, and provides a basis for the operation and advertising strategies of rural destinations to attract tourists and promote their sustainable development.


Assuntos
COVID-19 , Motivação , Humanos , Publicidade , China/epidemiologia , COVID-19/epidemiologia , Turismo , População Rural
6.
Cell Death Dis ; 14(12): 810, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065978

RESUMO

Ferroptosis, which is driven by iron-dependent lipid peroxidation, plays an essential role in liver ischemia-reperfusion injury (IRI) during liver transplantation (LT). Gp78, an E3 ligase, has been implicated in lipid metabolism and inflammation. However, its role in liver IRI and ferroptosis remains unknown. Here, hepatocyte-specific gp78 knockout (HKO) or overexpressed (OE) mice were generated to examine the effect of gp78 on liver IRI, and a multi-omics approach (transcriptomics, proteomics, and metabolomics) was performed to explore the potential mechanism. Gp78 expression decreased after reperfusion in LT patients and mice with IRI, and gp78 expression was positively correlated with liver damage. Gp78 absence from hepatocytes alleviated liver damage in mice with IRI, ameliorating inflammation. However, mice with hepatic gp78 overexpression showed the opposite phenotype. Mechanistically, gp78 overexpression disturbed lipid homeostasis, remodeling polyunsaturated fatty acid (PUFA) metabolism, causing oxidized lipids accumulation and ferroptosis, partly by promoting ACSL4 expression. Chemical inhibition of ferroptosis or ACSL4 abrogated the effects of gp78 on ferroptosis and liver IRI. Our findings reveal a role of gp78 in liver IRI pathogenesis and uncover a mechanism by which gp78 promotes hepatocyte ferroptosis by ACSL4, suggesting the gp78-ACSL4 axis as a feasible target for the treatment of IRI-associated liver damage.


Assuntos
Ferroptose , Hepatócitos , Hepatopatias , Receptores do Fator Autócrino de Motilidade , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Hepatócitos/enzimologia , Inflamação/metabolismo , Hepatopatias/metabolismo , Traumatismo por Reperfusão/metabolismo , Transplante de Fígado , Receptores do Fator Autócrino de Motilidade/genética , Receptores do Fator Autócrino de Motilidade/metabolismo , Coenzima A Ligases
7.
Diagnostics (Basel) ; 13(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38132251

RESUMO

Our image recognition system employs a deep learning model to differentiate between the left and right upper limbs in images, allowing doctors to determine the correct surgical position. From the experimental results, it was found that the precision rate and the recall rate of the intelligent image recognition system for preventing wrong-site upper limb surgery proposed in this paper could reach 98% and 93%, respectively. The results proved that our Artificial Intelligence Image Recognition System (AIIRS) could indeed assist orthopedic surgeons in preventing the occurrence of wrong-site left and right upper limb surgery. At the same time, in future, we will apply for an IRB based on our prototype experimental results and we will conduct the second phase of human trials. The results of this research paper are of great benefit and research value to upper limb orthopedic surgery.

8.
J Transl Med ; 21(1): 739, 2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37858181

RESUMO

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.


Assuntos
Hepatócitos , Insulinas , Hepatopatias , Traumatismo por Reperfusão , Animais , Camundongos , Antioxidantes/metabolismo , Apoptose/genética , Glucose/metabolismo , Hepatectomia/efeitos adversos , Hepatócitos/metabolismo , Hepatócitos/patologia , Hipóxia/complicações , Hipóxia/genética , Hipóxia/metabolismo , Insulinas/metabolismo , Fígado/irrigação sanguínea , Fígado/lesões , Fígado/metabolismo , Fígado/patologia , Hepatopatias/genética , Hepatopatias/metabolismo , Hepatopatias/patologia , Hepatopatias/cirurgia , Transplante de Fígado/efeitos adversos , Fosfatos/metabolismo , Fosfatos/farmacologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle
9.
bioRxiv ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37662359

RESUMO

Background: Sex differences impact Alzheimer's disease (AD) neuropathology, but cell-to-network level dysfunctions in the prodromal phase are unclear. Alterations in hippocampal excitation-inhibition balance (EIB) have recently been linked to early AD pathology. Objective: Examine how AD risk factors (age, APOE-ɛ4, amyloid-ß) relate to hippocampal EIB in cognitively normal males and females using connectome-level measures. Methods: Individuals from the OASIS-3 cohort (age 42-95) were studied (N = 437), with a subset aged 65+ undergoing neuropsychological testing (N = 231). Results: In absence of AD risk factors (APOE-ɛ4/Aß+), whole-brain EIB decreases with age more significantly in males than females (p = 0.021, ß = -0.007). Regression modeling including APOE-ɛ4 allele carriers (Aß-) yielded a significant positive AGE-by-APOE interaction in the right hippocampus for females only (p = 0.013, ß = 0.014), persisting with inclusion of Aß+ individuals (p = 0.012, ß = 0.014). Partial correlation analyses of neuropsychological testing showed significant associations with EIB in females: positive correlations between right hippocampal EIB with categorical fluency and whole-brain EIB with the trail-making test (p < 0.05). Conclusion: Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOE-ɛ4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOE-ɛ4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population.

10.
J Alzheimers Dis ; 95(4): 1449-1467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37718795

RESUMO

BACKGROUND: Sex differences impact Alzheimer's disease (AD) neuropathology, but cell-to-network level dysfunctions in the prodromal phase are unclear. Alterations in hippocampal excitation-inhibition balance (EIB) have recently been linked to early AD pathology. OBJECTIVE: Examine how AD risk factors (age, APOEɛ4, amyloid-ß) relate to hippocampal EIB in cognitively normal males and females using connectome-level measures. METHODS: Individuals from the OASIS-3 cohort (age 42-95) were studied (N = 437), with a subset aged 65+ undergoing neuropsychological testing (N = 231). RESULTS: In absence of AD risk factors (APOEɛ4/Aß+), whole-brain EIB decreases with age more significantly in males than females (p = 0.021, ß= -0.007). Regression modeling including APOEɛ4 allele carriers (Aß-) yielded a significant positive AGE-by-APOE interaction in the right hippocampus for females only (p = 0.013, ß= 0.014), persisting with inclusion of Aß+ individuals (p = 0.012, ß= 0.014). Partial correlation analyses of neuropsychological testing showed significant associations with EIB in females: positive correlations between right hippocampal EIB with categorical fluency and whole-brain EIB with the Trail Making Test (p < 0.05). CONCLUSIONS: Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOEɛ4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOEɛ4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Feminino , Masculino , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Envelhecimento/patologia , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia
11.
Nat Commun ; 14(1): 4226, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37454222

RESUMO

The role of microbial interactions and the underlying mechanisms that shape complex biofilm communities are poorly understood. Here we employ a microfluidic chip to represent porous subsurface environments and show that cooperative microbial interactions between free-living and biofilm-forming bacteria trigger active spatial segregation to promote their respective dominance in segregated microhabitats. During initial colonization, free-living and biofilm-forming microbes are segregated from the mixed planktonic inoculum to occupy the ambient fluid and grain surface. Contrary to spatial exclusion through competition, the active spatial segregation is induced by cooperative interactions which improves the fitness of both biofilm and planktonic populations. We further show that free-living Arthrobacter induces the surface colonization by scavenging the biofilm inhibitor, D-amino acids and receives benefits from the public goods secreted by the biofilm-forming strains. Collectively, our results reveal how cooperative microbial interactions may contribute to microbial coexistence in segregated microhabitats and drive subsurface biofilm community succession.


Assuntos
Biofilmes , Interações Microbianas , Porosidade , Bactérias , Plâncton
12.
Mol Biomed ; 4(1): 22, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37482600

RESUMO

In this study, we aim to develop and validate a radiomics model for pretreatment prediction of RPS6K expression in hepatocellular carcinoma (HCC) patients, thus helping clinical decision-making of mTOR-inhibitor (mTORi) therapy. We retrospectively enrolled 147 HCC patients, who underwent curative hepatic resection at First Affiliated Hospital Zhejiang University School of Medicine. RPS6K expression was determined with immunohistochemistry staining. Patients were randomly split into training or validation cohorts on a 7:3 ratio. Radiomics features were extracted from T2-weighted and diffusion-weighted images. Machine learning algorithms including multiple logistic regression (MLR), supporting vector machine (SVM), random forest (RF), and artificial neural network (ANN) were applied to construct the predictive model. A nomogram was further built to visualize the possibility of RPS6K expression. The area under the receiver operating characteristic (AUC) was used to evaluate the performance of diagnostic models. 174 radiomics features were confirmed correlated with RPS6K expression. Amongst all built models, the ANN-based hybrid model exhibited best predictive ability with AUC of 0.887 and 0.826 in training and validation cohorts. ALB was identified as the key clinical index, and the nomogram displayed further improved ability with AUC of 0.917 and 0.845. In this study, we proved MRI-based radiomics model and nomogram can accurately predict RPS6K expression non-invasively, thus providing help for clinical decision making for mTORi therapy.

13.
Math Biosci Eng ; 20(7): 12320-12340, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37501444

RESUMO

Permanent magnet brake (PMB) is a safe and effective braking mechanism used to stop and hold the load in place. Due to its complex structure and high reliability, assessing the reliability of PMB remains a challenge. The main difficulty lies in that there are several performance indicators reflecting the health state of PMB, and they are correlated with each other. In order to assess the reliability of PMB more accurately, a constant stress accelerated degradation test (ADT) is carried out to collect degradation data of two main performance indicators in PMB. An accelerated bivariate Wiener degradation model is proposed to analyse the ADT data. In the proposed model, the relationship between degradation rate and stress levels is described by Arrhenius model, and a common random effect is introduced to describe the unit-to-unit variation and correlation between the two performance indicators. The Markov Chain Monte Carlo (MCMC) algorithm is performed to obtain the point and interval estimates of the model parameters. Finally, the proposed model and method are applied to analyse the accelerated degradation data of PMB, and the results show that the reliability of PMB at the used condition can be quantified quite well.

14.
Int J Mol Sci ; 24(12)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37373161

RESUMO

Common buckwheat (Fagopyrum esculentum M.) is an important traditional miscellaneous grain crop. However, seed-shattering is a significant problem in common buckwheat. To investigate the genetic architecture and genetic regulation of seed-shattering in common buckwheat, we constructed a genetic linkage map using the F2 population of Gr (green-flower mutant and shattering resistance) and UD (white flower and susceptible to shattering), which included eight linkage groups with 174 loci, and detected seven QTLs of pedicel strength. RNA-seq analysis of pedicel in two parents revealed 214 differentially expressed genes DEGs that play roles in phenylpropanoid biosynthesis, vitamin B6 metabolism, and flavonoid biosynthesis. Weighted gene co-expression network analysis (WGCNA) was performed and screened out 19 core hub genes. Untargeted GC-MS analysis detected 138 different metabolites and conjoint analysis screened out 11 DEGs, which were significantly associated with differential metabolites. Furthermore, we identified 43 genes in the QTLs, of which six genes had high expression levels in the pedicel of common buckwheat. Finally, 21 candidate genes were screened out based on the above analysis and gene function. Our results provided additional knowledge for the identification and functions of causal candidate genes responsible for the variation in seed-shattering and would be an invaluable resource for the genetic dissection of common buckwheat resistance-shattering molecular breeding.


Assuntos
Fagopyrum , Fagopyrum/genética , Fagopyrum/metabolismo , Transcriptoma , Mapeamento Cromossômico , Sementes/metabolismo , Perfilação da Expressão Gênica
15.
Artigo em Inglês | MEDLINE | ID: mdl-37206660

RESUMO

Purpose: To examine the relationship between features of daily measured step count trajectories and clinical outcomes among people with comorbid obesity and depression in the ENGAGE-2 Trial. Methods: This post hoc analysis used data from the ENGAGE-2 trial where adults (n=106) with comorbid obesity (BMI ≥30.0 or 27.0 if Asian) and depressive symptoms (Patient Health Questionnaire-9 score ≥10) were randomized (2:1) to receive the experimental intervention or usual care. Daily step count trajectories over the first 60 days (Fitbit Alta HR) were characterized using functional principal component analyses. 7-day and 30-day trajectories were also explored. Functional principal component scores that described features of step count trajectories were entered into linear mixed models to predict weight (kg), depression (Symptom Checklist-20), and anxiety (Generalized Anxiety Disorder Questionnaire-7) at 2-months (2M) and 6-months (6M). Results: Features of 60-day step count trajectories were interpreted as overall sustained high, continuous decline, and disrupted decline. Overall sustained high step count was associated with low anxiety (2M, ß=-0.78, p<.05; 6M, ß=-0.80, p<.05) and low depressive symptoms (6M, ß=-0.15, p<.05). Continuous decline in step count was associated with high weight (2M, ß=0.58, p<.05). Disrupted decline was not associated with clinical outcomes at 2M or 6M. Features of 30-day step count trajectories were also associated with weight (2M, 6M), depression (6M), and anxiety (2M, 6M); Features of 7-day step count trajectories were not associated with weight, depression, or anxiety at 2M or 6M. Conclusions: Features of step count trajectories identified using functional principal component analysis were associated with depression, anxiety, and weight outcomes among adults with comorbid obesity and depression. Functional principal component analysis may be a useful analytic method that leverages daily measured physical activity levels to allow for precise tailoring of future behavioral interventions.

16.
J Hazard Mater ; 456: 131651, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37245361

RESUMO

Extracellular polymeric substances (EPS) play a crucial role in controlling the mobility and bioavailability of heavy metal(loid)s in water, soils, and sediments. The formation of EPS-mineral complex changes the reactivity of the end-member materials. However, little is known about the adsorption and redox mechanisms of arsenate (As(V)) in EPS and EPS-mineral complexes. Here we examined the reaction sites, valence state, thermodynamic parameters and distribution of As in the complexes using potentiometric titration, isothermal titration calorimetry (ITC), FTIR, XPS, and SEM-EDS. The results showed that ∼54% of As(V) was reduced to As(III) by EPS, potentially driven by an enthalpy change (ΔH) of - 24.95 kJ/mol. The EPS coating on minerals clearly affected the reactivity to As(V). The strong masking of functional sites between EPS and goethite inhibited both the adsorption and reduction of As. In contrast, the weak binding of EPS onto montmorillonite retained more reactive sites for the reaction with As. Meanwhile, montmorillonite facilitated the immobilization of As to EPS through the formation of As-organic bounds. Our findings deepen the understanding of EPS-mineral interfacial reactions in controlling the redox and mobility of As, and the knowledge is important for predicting the behavior of As in natural environments.

17.
Funct Integr Genomics ; 23(2): 123, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37055658

RESUMO

Multi-pistil trait in wheat is of great potential value in plant development research and crop breeding. Our previous studies identified the Pis1 locus that causes three pistils in wheat by genetic mapping using multiple DNA marker systems. However, there are still 26 candidate genes on the locus, and the causal gene remains to be found. In this study, we aimed to approach the molecular mechanism of multi-pistil formation. Comparative RNA sequencing (RNA-Seq) during the pistil formation was undertaken in four wheat lines: a three-pistil mutant TP, a single-pistil TILLING mutant of TP (SP), a three-pistil near-isogenic line CM28TP with the background of cultivar Chunmai 28 (CM28), and CM28. Electron microscopic analysis specified probable developmental stages of young spikes for the three-pistil formation. mRNA sequencing in the young spikes of the four lines represented 253 down-regulated genes and 98 up-regulated genes in both three-pistil lines, which included six potential genes for ovary development. Weighted gene co-expression analysis represented three-pistil trait-associated transcription factor-like genes, among which one hub gene, ARF5, was the most highlighted. ARF5 is on the Pis1 locus and an orthologue of MONOPTEROS which mediates tissue development in Arabidopsis. qRT-PCR validation implies that the deficiency of ARF5 underlies the three-pistil formation in wheat.


Assuntos
Regulação da Expressão Gênica de Plantas , Triticum , Triticum/genética , Melhoramento Vegetal , Marcadores Genéticos , Flores/genética
18.
Front Microbiol ; 14: 1115300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937304

RESUMO

Soil microbial diversity is important for maintaining ecosystem functions. However, the linkage between microbial diversity, especially rare and abundant bacterial diversity, and carbon decomposition remains largely unknown. In this study, we assessed the establishment and maintenance of rare and abundant bacterial α-diversities at the taxonomic and phylogenetic levels and their linkages with soil carbon decomposition separately in four Chinese woodlands. Compared to abundant bacteria, rare bacteria showed higher community diversity, tighter phylogenetic clustering, wider environmental breadth, stronger phylogenetic signals, and higher functional redundancy. The assembly of the abundant bacterial subcommunity was governed by stochastic (59.2%) and deterministic (41.8%) processes, whereas the assembly of the rare bacterial subcommunity was mainly dominated by deterministic processes (85.8%). Furthermore, total phosphorus, soil pH, and ammonium nitrogen balanced stochastic and deterministic processes in both rare and abundant bacterial subcommunities. Our results reveal that rare bacteria displayed stronger environmental adaptability and environmental constraint. Importantly, the α-diversities of rare taxa, rather than abundant taxa, were significantly related to carbon decomposition. This study provides a holistic understanding of biogeographic patterns of abundant and rare bacteria and their α-diversities in relation to carbon decomposition, thus helping us better predict and regulate carbon dynamics under the background of global climate change.

19.
Biomed Chromatogr ; 37(6): e5622, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36898359

RESUMO

Helicobacter pylori (H. pylori), as a harmful bacteria associated with gastric cancer, can have adverse effects on human normal flora and metabolism. However, the effects of H. pylori on human metabolism have not been fully elucidated. The 13 C breathing test was used as the basis for distinguishing negative and positive groups. Serum samples were collected from the two groups for targeted quantitative metabolomics detection; multidimensional statistics were used, including partial least squares discriminant analysis (PLS-DA), principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and differential metabolites were screened. Unidimensional statistics combined with multidimensional statistics were used to further screen potential biomarkers, and finally pathway analysis was performed. SPSS 21.0 software package was used for statistical analysis of experimental data. Multivariate statistical analysis such as PLS-DA, PCA, and OPLS-DA was performed using Simca-P 13.0 to search for differential metabolites. This study confirmed that H. pylori caused significant changes in human metabolism. In this experiment, 211 metabolites were detected in the serum of the two groups. Multivariate statistical analysis showed that PCA of metabolites was not significantly different between the two groups. PLS-DA indicated that the serum of the two groups was well clustered. There were significant differences in metabolites between OPLS-DA groups. By setting the variable importance in projection (VIP) threshold as one and the corresponding P-value <0.05, a total of 40 metabolites were screened in this study. P <0.05 and ∣log2FC∣>0 (where FC is the fold change) were used together as a unidimensional statistical filter condition. The analysis found that the expression of 15 metabolites such as propionic acid, acetic acid, adipic acid increased, and the metabolism of six products such as deoxycholic acid (DCA), 4-hydroxyphenylpyruvic acid, pyruvic acid decreased. P <0.05, false discovery rate <0.5, ∣log2FC∣>1, and OPLSDA_VIP>1 were used together as a condition for filter screening potential biomarkers. Four potential biomarkers were screened, which were sebacic acid, isovaleric acid, DCA, and indole-3-carboxylic acid. Finally, the different metabolites were added to the pathway-associated metabolite sets (SMPDB) library for the corresponding pathway enrichment analysis. The significant abnormal metabolic pathways were taurine and subtaurine metabolism, tyrosine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, etc. This study shows that H. pylori has an impact on human metabolism. Not only a variety of metabolites have significant changes, but also metabolic pathways are abnormal, which may be the reason for the high risk of H. pylori causing gastric cancer.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Humanos , Espectrometria de Massas em Tandem , Metabolômica/métodos , Cromatografia Líquida , Biomarcadores , Ácido Acético
20.
Am J Clin Nutr ; 117(4): 717-730, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36796440

RESUMO

BACKGROUND: The microbiome-gut-brain-axis (MGBA) is emerging as an important mechanistic link between diet and mental health. The role of significant modifiers of the MGBA, including gut microbial metabolites and systemic inflammation, in individuals comorbid with obesity and mental disorders, is under-investigated. OBJECTIVES: This exploratory analysis examined associations among microbial metabolites-fecal SCFAs, plasma inflammatory cytokines, and diet with depression and anxiety scores in adults comorbid with obesity and depression. METHODS: Stool and blood were obtained from a subsample (n = 34) of participants enrolled in an integrated behavioral intervention for weight loss and depression. Pearson partial correlation and multivariate analyses determined associations among changes in fecal SCFAs (propionic, butyric, acetic, and isovaleric acids), plasma cytokines [C-reactive protein, interleukin 1 beta, interleukin 1 receptor antagonist (IL-1RA), interleukin 6, and TNF-α], and 35 dietary markers over 2 mo, and changes in SCL-20 (Depression Symptom Checklist 20-item) and GAD-7 (Generalized Anxiety Disorder 7-Item) scores over 6 mo. RESULTS: Changes in the SCFAs and TNF-α at 2 mo were positively associated (standardized coefficients: 0.06-0.40; 0.03-0.34) with changes in depression and anxiety scores at 6 mo, whereas changes in IL-1RA at 2 mo were inversely associated (standardized coefficients: -0.24; -0.05). After 2 mo, changes in 12 dietary markers, including animal protein, were associated with changes in SCFAs, TNF-α, or IL-1RA at 2 mo (standardized coefficients: -0.27 to 0.20). Changes in 11 dietary markers, including animal protein, at 2 mo were associated with changes in depression or anxiety symptom scores at 6 mo (standardized coefficients: -0.24 to 0.20; -0.16 to 0.15). CONCLUSIONS: Gut microbial metabolites and systemic inflammation may be biomarkers of importance within the MGBA, linking dietary markers, such as animal protein intake, to depression and anxiety for individuals with comorbid obesity. These findings are exploratory and warrant replication.


Assuntos
Citocinas , Fator de Necrose Tumoral alfa , Animais , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Depressão , Projetos Piloto , Ácidos Graxos Voláteis/análise , Dieta , Obesidade , Inflamação/metabolismo , Ansiedade , Transtornos de Ansiedade
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