Metabolic associated fatty liver disease (MAFLD) is a new definition for liver disease associated with known metabolic dysfunction. Based on new diagnostic criteria, we aimed to investigate its ...prevalence and risk factors in Chinese population.
We conducted this study in a health examination population who underwent abdominal ultrasonography in China. The diagnosis of MAFLD was based on the new diagnostic criteria. The characteristics of the MAFLD population, as well as the associations between MAFLD and metabolic abnormalities, were explored. Mann-Whitney U test and chi-square test were performed to compare different variables. Binary logistic regression was used to determine the risk factors for MAFLD.
Among 139,170 subjects, the prevalence of MAFLD was 26.1% (males: 35.4%; females: 14.1%). The prevalence based on female menopausal status, that is, premenopausal, perimenopausal, and postmenopausal, was 6.1%, 16.8%, and 30.2%, respectively. In different BMI groups (underweight, normal, overweight and obese), the prevalence was 0.1%, 4.0%, 27.4% and 59.8%, respectively. The proportions of abnormal metabolic features in the MAFLD group were significantly higher than those in the non-MAFLD group, as was the proportion of elevated alanine aminotransferase (ALT) (42.5% vs. 11%, P < 0.001). In nonobese individuals with MAFLD, the proportions of abnormal metabolic features were also all significantly higher than those in nonobese individuals without MAFLD. The prevalence of metabolic syndrome (MS), dyslipidaemia, and hyperuricaemia, respectively, in the MAFLD group (53.2%, 80.0%, and 45.0%) was significantly higher than that in the non-MAFLD group (10.1%, 41.7%, and 16.8%). Logistic regression revealed that age, BMI, waist circumference, ALT, triglycerides, fasting glucose, uric acid and platelet count were associated with MAFLD.
MAFLD is prevalent in China and varies considerably among different age, sex, BMI, and female menopausal status groups. MAFLD is related to metabolic disorders, especially obesity, while metabolic disorders also play important roles in the occurrence of MAFLD in nonobese individuals. MAFLD patients exhibit a high prevalence of MS, dyslipidaemia, hyperuricaemia, and elevated liver enzymes. MAFLD tends to coexist with systemic metabolic disorders, and a deep inner relationship may exist between MAFLD and MS. Metabolic disorders should be considered to improve the management of MAFLD.
Reliable and noninvasive biomarkers for the early diagnosis of non‐small‐cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early ...diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver‐operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early‐stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.
Malate dehydrogenase 2 was significantly elevated both in urine and in cancer tissues of NSCLC patients. The level of MDH2 in urine could serve as an assistant biomarker for the early diagnosis of NSCLC.
Abstract
Context
Thyroid function variation within the thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed ...definition.
Objective
We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD.
Methods
Data of 10 666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within the thyroxine reference range was defined based on thyroid-stimulating hormone (TSH) levels: subclinical hyperthyroidism, <0.39 mIU/L; strict-normal thyroid function, 0.39-2.5 mIU/L; and low thyroid function, >2.5 mIU/L, which comprised low-normal thyroid function (2.5-4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and Cox regression were used in multivariate analysis.
Results
Low thyroid function is independently associated with MAFLD (odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in the total population (hazard ratio HR for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99); meanwhile, in the low-normal thyroid function group, an increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in the total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality.
Conclusions
Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in the MAFLD population. Reevaluation of TSH reference range should be considered.
Summary
The simultaneous symbiosis of leguminous plants with two root mutualists, endophytic fungi and rhizobia is common in nature, yet how two mutualists interact and co‐exist before infecting ...plants and the concomitant effects on nodulation are less understood.
Using a combination of metabolic analysis, fungal deletion mutants and comparative transcriptomics, we demonstrated that Bradyrhizobium and a facultatively biotrophic fungus, Phomopsis liquidambaris, interacted to stimulate fungal flavonoid production, and thereby primed Bradyrhizobial nodulation signaling, enhancing Bradyrhizobial responses to root exudates and leading to early nodulation of peanut (Arachis hypogaea), and such effects were compromised when disturbing fungal flavonoid biosynthesis.
Stress sensitivity assays and reactive oxygen species (ROS) determination revealed that flavonoid production acted as a strategy to alleviate hyphal oxidative stress during P. liquidambaris–Bradyrhizobial interactions. By investigating the interactions between P. liquidambaris and a collection of 38 rhizobacteria, from distinct bacterial genera, we additionally showed that the flavonoid‐ROS module contributed to the maintenance of fungal and bacterial co‐existence, and fungal niche colonization under soil conditions.
Our results demonstrate for the first time that rhizobial nodulation signaling can be primed by fungi before symbiosis with host plants and highlight the importance of flavonoid in tripartite interactions between legumes, beneficial fungi and rhizobia.
Fungal endophytes play critical roles in helping plants adapt to adverse environmental conditions. The root endophyte Phomopsis liquidambaris can promote the growth and disease control of peanut ...plants grown under monocropping systems; however, how such beneficial traits are produced is largely unknown. Since the plant endophytic microbiome is directly linked to plant growth and health, and the composition of which has been found to be potentially influenced by microbial inoculants, this study aims to clarify the roles of root endophytic bacterial communities in P. liquidambaris-mediated plant fitness enhancement under monocropping conditions. Here, we found that P. liquidambaris inoculation induced significant changes in the root bacterial community: enriching some beneficial bacteria such as Bradyrhizobium sp. and Streptomyces sp. in the roots, and improving the core microbial-based interaction network. Next, we assembled and simplified a synthetic community (SynII) based on P. liquidambaris-derived key taxa, including Bacillus sp. HB1, Bacillus sp. HB9, Burkholderia sp. MB7, Pseudomonas sp. MB2, Streptomyces sp. MB6, and Bradyrhizobium sp. MB15. Furthermore, the application of the simplified synthetic community suppressed root rot caused by Fusarium oxysporum, promoted plant growth, and increased peanut yields under continuous monocropping conditions. The resistance of synII to F. oxysporum is related to the increased activity of defense enzymes. In addition, synII application significantly increased shoot and root biomass, and yield by 35.56%, 81.19%, and 34.31%, respectively. Collectively, our results suggest that the reshaping of root core microbiota plays an important role in the probiotic-mediated adaptability of plants under adverse environments.
Fatty liver index (FLI) is the most recognized blood biomarker for diagnosis of hepatic steatosis (HS), but lacks the reliable specific cut-off points (COPs). Therefore, we aim to investigate the ...population-specific COPs of FLI based on the results of liver ultrasound transient elastography (LUTE) and conventional ultrasonography in the National Health and Nutrition Examination Survey (NHANES).
5948 participants who underwent LUTE from the NHANES 2017-2018 and 14,797 participants who underwent conventional ultrasonography from the Third NHANES (NHANES III) were recruited. FLI was calculated by using body mass index (BMI), waist circumference (WC), triglyceride, and gamma-glutamyl transferase, and its optimal COPs in a specific population (stratified by sex, BMI, and WC) were obtained from receiver operator characteristics (ROC) curve with ultrasonic-diagnosed HS as the reference standard.
Based on LUTE in NHANES 2017-2018, the prevalence of HS and metabolic dysfunction-associated fatty liver disease (MAFLD) were 58.7% and 56.2%, respectively, and the optimal COP of FLI for HS diagnosis in the overall population was 45.60, with an area under ROC curve (AUROC) of 0.833 (0.822-0.844). Based on conventional ultrasonography in NHANES III, the prevalence of HS and MAFLD were 34.4% and 27. 9%, respectively, and the optimal COP of FLI for HS was 59.5, with an AUROC of 0.681 (0.671-0.691). With the increase of BMI and WC, the COPs increased gradually with significant differences between different groups. Compared with conventional ultrasonography, the COPs of FLI based on LUTE were much more precise, with higher diagnostic ability. The population-specific COPs of FLI stratified by gender, WC, and BMI were tabulated.
In the United States, the incidences of HS and MAFLD were high, especially when assessed by LUTE. The FLI based on LUTE is well capable of predicting HS when stratified by gender, WC, and BMI.
Iron (Fe) deficiency in alkaline calcium soil is a problem that needs to be solved urgently as Fe is an essential and commonly limiting nutrient for plants. Endophytic fungus,
(
), has been reported ...to promote Fe absorption in peanuts (
L.), however, the mechanisms remain unclear. Under prolonged Fe deficiency, an increase in hydrogen peroxide (H
O
) often triggers a series of signaling events and leads to the inhibition of Fe acquisition. The main purpose of this study was to explore whether and how the endophytic fungus
promote Fe absorption in peanut through regulating H
O
and assisting in resisting oxidative stress. In this study, we detected the Fe deficiency-induced transcription factor (
), Fe
transporter (
1), and ferric reduction oxidase 2 (
) of peanuts, and confirmed that they were negatively related to Fe concentration. Similarly,
1, and
were also inhibited by H
O
. The addition of
reduces H
O
under Fe-deficiency with an increase in Fe content, while the exogenous addition of H
O
further decreases it, and the addition of catalase (CAT) under Fe-deficiency reverses this phenomenon. Through transcriptome analysis, we proved that the expression of
1,
and CAT are consistent with our hypothesis, and
has a stress-mitigating effect on peanuts mainly via CAT, glutathione peroxidase, and malondialdehyde. Our study proved the Fe-absorption promoting effect and stress mitigation effect of
under Fe-deficiency in peanuts, and their combined usage may help peanuts grow better.
Fine and dispersed Mg–Ti–oxide inclusions, which act as heterogeneous nucleation sites for intragranular ferrite, have been acknowledged as an effective method for grain refinement. In this paper, ...the nucleation and growth mechanisms of ferrite on Mg–Ti-oxides surface were investigated through first-principles calculations and solid-state pressure bonding experiments. The calculated results show that the formation of cation vacancies is the limiting step for Mn solute atom absorption by Mg–Ti-oxides. As determined by the lower covalency and ionicity of the Mg–O bond compared to the Ti–O bond in Mg–Ti-oxides, Mn atoms will be efficiently absorbed by occupying the Mg vacancies. The experimental results demonstrate that MgTiO3 with the maximum Mn-depleted zone (MDZ) width is the most effective for ferrite nucleation, which is consistent with the calculation results. As a representative, the Fe(110)/MgTiO3(001) interface with the lowest planar disregistry (3.16%) was selected to analyze growth behaviors. Due to charge accumulation and variation, Fe atoms are more likely to gather on the Mg–O terminal MgTiO3(001) surface and form (Mg–O)–Fe-1 interfaces. Its adhesion work and interface energy are 1.74 and 2.46 J/m2, respectively. The present study illustrates the nucleation and growth mechanisms of ferrite on Mg–Ti-oxides, providing theoretical support for the application of Mg–Ti-oxide inclusions in oxide metallurgy.
Background
Effective biomarkers for early diagnosis of lung cancer are needed. Previous studies have indicated positive associations between abnormal circulating cytokines and the etiology of lung ...cancer.
Methods
Blood samples were obtained from 286 patients with pretreatment lung cancer and 80 healthy volunteers. Circulating cytokine levels were detected with a Luminex assay and enzyme-linked immunosorbent assay (ELISA). Urine samples were obtained from 284 patients and 122 healthy volunteers. CXC chemokine ligand 14 (CXCL14) expression in tumors and nontumor regions of lung tissues from 133 lung cancer cases was detected by immunohistochemical (IHC) staining and immunofluorescence (IF) staining of formalin fixed paraffin-embedded (FFPE) tissues.
Results
Compared with healthy volunteers, a 65.7-fold increase was observed in the level of CXCL14 in the plasma of lung cancer patients, and a 1.7-fold increase was observed in the level of CXCL14 in the urine of lung cancer patients, achieving a 0.9464 AUC (area under the curve) value and a 0.6476 AUC value for differentiating between lung cancer patients and healthy volunteers, respectively. Stromal CXCL14 expression was significantly associated with advanced pathologic stage (
P
<0.001), pathologic N stage (
P
<0.001), and recurrence and metastasis (
P
=0.014). Moreover, multivariate analysis suggested stromal CXCL14 expression as an independent predictor of DFS and OS.
Conclusions
Our study demonstrates that CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.
Impact
CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.
Background
Circulating genetically abnormal cells (CACs) with specific chromosome variations have been confirmed to be present in non‐small cell lung cancer (NSCLC). However, the diagnostic ...performance of CAC detection remains unclear. This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC.
Methods
In this prospective study, a total of 339 participants (261 lung cancer patients and 78 healthy volunteers) were enrolled. An antigen‐independent fluorescence in situ hybridization was used to enumerate the number of CACs in peripheral blood.
Results
Patients with early‐stage NSCLC were found to have a significantly higher number of CACs than those of healthy participants (1.34 vs. 0.19; P < 0.001). The CAC test displayed an area under the receiver operating characteristic (ROC) curve of 0.76139 for discriminating stage I NSCLC from healthy participants with 67.2% sensitivity and 80.8% specificity, respectively. Compared with serum tumor markers, the sensitivity of CAC assays for distinguishing early‐stage NSCLC was higher (67.2% vs. 48.7%, P < 0.001), especially in NSCLC patients with small nodules (65.4% vs. 36.5%, P = 0.003) and ground‐glass nodules (pure GGNs: 66.7% vs. 40.9%, P = 0.003; mixed GGNs: 73.0% vs. 43.2%, P < 0.001).
Conclusions
CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC.
Key points
What this study adds: This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC.
Significant findings of the study: CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC.
Workflow of circulating genetically abnormal cells enumeration.
Circulating genetically abnormal cell detection in early stage non‐small‐cell lung cancer was feasible.
Circulating genetically abnormal cell test has good stability and adaptability for different patient populations.
Circulating genetically abnormal cells could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC.