Impacts of Triglyceride Glucose-Waist to Height Ratio on Diabetes Incidence: A Secondary Analysis of A Population-Based Longitudinal Data

BackgroundThe anthropometric indices (body mass index [BMI], waist circumference [WC] and waist-to-height ratio [WHtR]), triglyceride-glucose (TyG) index and TyG-related indicators (TyG-WHtR, TyG-BMI, TyG-WC) have been well documented to be highly correlated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, it was not immediately obvious which indicator would be optimal for screening people at risk of T2DM. Hence, this study intended to compare the predictive effects of the aforementioned markers on T2DM and to investigate the relation between baseline TyG-WHtR and incident T2DM.MethodsThis longitudinal study included 15464 study population who were involved in the NAGALA (NAfld in the Gifu Area Longitudinal Analysis) study from 2004 to 2015. The TyG index was defined as ln [FPG (mg/dL) ×fasting TG (mg/dL)/2]. And the TyG-WHtR was calculated as TyG index ×WHtR. We divided the participants into four groups according to the TyG-WHtR quartiles. The primary endpoint was the incidence of diabetes.ResultsAfter a median follow-up of 5.4 years, 2.4% (373/15464) participants developed diabetes. The incidence of diabetes increased with ascending TyG-WHtR quartiles (P for trend<0.001). Multivariable Cox proportional hazard analysis showed that a one-unit increase in TyG-WHtR was independently correlated with a 2.714-fold higher risk of diabetes [hazard ratio (HR) 2.714, 95% confidence interval (CI) 1.942-3.793; P<0.001). Stratification analysis revealed that increased TyG-WHtR (per 1-unit) was consistently correlated with diabetes incidence in different subgroups. Moreover, TyG-WHtR outperformed the other parameters by presenting the biggest area under the ROC curve (AUC) in men (AUC 0.746, 95% CI 0.716-0.776, P<0.001). However, all pairwise comparisons of AUC between TyG-WHtR and other indicators were not statistically different except TyG-WHtR vs. WHtR in women.ConclusionsA high TyG-WHtR is an important predictor of the increased cumulative risk of diabetes development. TyG-WHtR outperforms TyG, WHtR, TyG-WC and TyG-BMI in screening individuals who are susceptible to T2DM, especially in men

Assessing the Impact of Air Pollution on Grain Yield of Winter Wheat - A Case Study in the North China Plain

The major wheat production region of China the North China Plain (NCP) is seriously affected by air pollution. In this study, yield of winter wheat (Triticum aestivum L.) was analyzed with respect to the potential impact of air pollution index under conditions of optimal crop management in the NCP from 2001 to 2012. Results showed that air pollution was especially serious at the early phase of winter wheat growth significantly influencing various weather factors. However, no significant correlations were found between final grain yield and the weather factors during the early growth phase. In contrast, significant correlations were found between grain yield and total solar radiation gap, sunshine hour gap, diurnal temperature range and relative humidity during the late growing phase. To disentangle the confounding effects of various weather factors, and test the isolated effect of air pollution induced changes in incoming global solar radiation on yield under ceteris paribus conditions, crop model based scenario-analysis was conducted. The simulation results of the calibrated Agricultural Production Systems Simulator (APSIM) model indicated that a reduction in radiation by 10% might cause a yield reduction by more than 10%. Increasing incident radiation by 10% would lead to yield increases of (only) 7%, with the effects being much stronger during the late growing phase compared to the early growing phase. However, there is evidence that APSIM overestimates the effect of air pollution induced changes on radiation, as it does not consider the changes in radiative properties of solar insulation, i.e. the relative increase of diffuse over direct radiation, which may partly alleviate the negative effects of reduced total radiation by air pollution. Concluding, the present study could not detect a significantly negative effect of air pollution on wheat yields in the NCP

CD151 Drives Cancer Progression Depending on Integrin α3β1 through EGFR Signaling in Non-Small Cell Lung Cancer

Background Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion. Methods First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied. Results High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs. Conclusions Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment

Three‐channel electrical impedance spectroscopy for field‐scale root phenotyping

AbstractElectrical impedance spectroscopy has long been considered a promising technique for noninvasive, in‐situ root investigation because of its sensitivity to anatomy and physiology. However, the complexity of the root system and its coupling with stem and soil have hindered the signal interpretation and methodological upscaling to field applications. This study addresses these key issues by introducing three‐channel acquisitions and their interpretation through Cole–Cole fitting. This solution could successfully decouple the impedance response of stem, roots, and soil, as well as provide convenient parametrization and comparison of their impedance signals. The methodological solution was tested on 80 wheat (Triticum aestivum L.) and 10 pecan [Carya illinoensis (Wangenh.) K. Koch] plants, the first extensive and field investigation. The investigation provided evidence of (a) proximal current leakage in herbaceous root systems, extending recent laboratory results and previous indirect field studies. (b) Major role of the plant stem, which has been a substantial concern raised in numerous studies. (c) Minor contribution from the soil, addressing the doubts on the comparability of results obtained in different soil conditions. All together, these evidences lead to indirect correlations between impedance signals and root traits. The explored solution is expected to support the adoption of the impedance spectroscopy, in line with the diffusion of multichannel impedance meters and growing interest in root physiology and phenotyping

Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: enhancing gut probiotics abundance and the tryptophan-melatonin pathway

Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5- hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.info:eu-repo/semantics/publishedVersio

The role of adiponectin in the association between abdominal obesity and type 2 diabetes: a mediation analysis among 232,438 Chinese participants

BackgroundAdiposity and adipokines are closely associated with obesity-related metabolic abnormalities, but little is known regarding whether abdominal obesity is linked to type 2 diabetes mellitus (T2DM) through circulating adiponectin levels. Thus, this large-population–based study was designed to investigate the mediating effect of adiponectin in the relationship between abdominal obesity and T2DM.MethodsA total of 232,438 adults who lived in Dongguan, Guangdong Province, China, were enrolled in the present study. The circulating adiponectin concentrations were measured using latex-enhanced immunoturbidimetric assay. The association between circulating adiponectin and other clinical parameters was detected by Spearman’s correlation analysis. Restricted cubic spline (RCS) regression was also used to address the non-linearity of the relationship between waist circumference and diabetes. Mediation analyses of circulating adiponectin were conducted using linear and logistic regression.ResultsSubjects with abdominal obesity had lower levels of circulating adiponectin (P < 0.001). The circulating adiponectin value was inversely related to BMI (r = −0.370, P < 0.001), waist circumference (r = −0.361, P < 0.001), and fasting plasma glucose (r = −0.221, P < 0.001). The RCS plot showed a non-linear relation linking waist circumference with T2DM (P for non-linearity < 0.001). Patients with abdominal obesity presented 2.062 times higher odds of T2DM in comparison with those with non-abdominal obesity (odds ratio, 2.062; 95% confidence interval, 1.969–2.161) after adjusting for confounders. In the mediation analyses, the circulating adiponectin mediated the association between abdominal obesity and T2DM, with a mediation effect of 41.02% after adjustments. The above results were consistent in both men and women.ConclusionThe relationship between abdominal obesity and T2DM is mediated through circulating adiponectin level in adults, suggesting that circulating adiponectin might be a potential predictor for controlling the adverse progression from adiposity to T2DM

CD151-α3β1 Integrin Complexes are Prognostic Markers of Glioblastoma and Cooperate with EGFR to Drive Tumor Cell Motility and Invasion

Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based cohort of 96 patient biopsies and TCGA dataset to evaluate the clinical significance of CD151 and α3β1 integrin. Functional and signaling analyses were also conducted to understand how these molecules promote the aggressiveness of glioblastoma at molecular and cellular levels. Results from our analyses showed that CD151 and α3 integrin were significantly elevated in glioblastomas at both protein and mRNA levels, and exhibited strong inverse correlation with patient survival (p \u3c 0.006). These adhesion molecules also formed tight protein complexes and synergized with EGF/EGFR to accelerate tumor cell motility and invasion. Furthermore, disruption of such complexes enhanced the survival of tumor-bearing mice in a xenograft model, and impaired activation of FAK and small GTPases. Also, knockdown- or pharmacological agent-based attenuation of EGFR, FAK or Graf (ARHGAP26)/small GTPase-mediated pathways markedly mitigated the aggressiveness of glioblastoma cells. Collectively, our findings provide clinical, molecular and cellular evidence of CD151-α3β1 integrin complexes as promising prognostic biomarkers and therapeutic targets for glioblastoma

Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

BackgroundCancer-associated fibroblasts (CAFs) are vital components of prominent cellular components in lower-grade gliomas (LGGs) that contribute to LGGs’ progression, treatment resistance, and immunosuppression. Epigenetic modification and immunity have significant implications for tumorigenesis and development.MethodsWe combined aberrant methylation and CAFs abundances to build a prognostic model and the impact on the biological properties of LGGs. Grouping based on the median CAFs abundances score of samples in the TCGA-LGGs dataset, differentially expressed genes and aberrantly methylated genes were combined for subsequent analysis.ResultsWe identified five differentially methylated and expressed genes (LAT32, SWAP70, GSAP, EMP3, and SLC2A10) and established a prognostic gene signature validated in the CGGA-LGGs dataset. Immunohistochemistry (IHC) and in vitro tests were performed to verify these expressions. The high-risk group increased in tumor-promoting immune cells and tumor mutational burden. Notably, risk stratification had different ICB sensitivities in LGGs, and there were also significant sensitivity differences for temozolomide and the other three novel chemotherapeutic agents.ConclusionOur study reveals characteristics of CAFs in LGGs, refines the direct link between epigenetics and tumor stroma, and might provide clinical implications for guiding tailored anti-CAFs therapy in combination with immunotherapy for LGGs patients

Stromal protein CCN family contributes to the poor prognosis in lower-grade gioma by modulating immunity, matrix, stemness, and metabolism

Background: The CCN family of stromal proteins is involved in the regulation of many important biological functions. However, the role of dysregulated CCN proteins in lower-grade glioma (LGG) remain less understand.Methods: The clinical significance of the CCN proteins was explored based on RNA-seq profiles from multiple cohorts. A CCNScore was constructed using LASSO regression analysis. The PanCanAtlas data and MEXPRESS database were employed to elucidate molecular underpinnings.Results: The expression of CCN4 was associated with poor prognosis in LGG. The CCNScore (CCN1 = 0.06, CCN4 = 0.86) showed implication in prognosis prediction, subtype assessment and therapy selection. The gene mutation pattern of the high-CCNScore group was similar with glioblastoma, including EGFR, PTEN, and NF1 mutation frequently. Besides, the high-CCNScore group was comprised of samples mainly classic-like and mesenchymal-like, had lower methylation levels, higher stemness, higher inflammation, higher levels of extracellular matrix remodel and dysfunction of metabolic pathways. On the other hand, the low-CCNScore group consisted mainly of IDH-mutation LGG, and was characterized by TP53, CIC, and ATRX gene mutations, hyper-methylation status, lower stemness, lower proliferation, immune quietness and low extracellular matrix stiffness.Conclusion: In summary, these results outlined the role of CCN family in LGG and provided a potential and promising therapeutic target

Rapid progression of subcutaneous glioblastoma: A case report and literature review

Extra-neural spread of glioblastoma (GBM) is extremely rare. We report a case of postoperative intracranial GBM spreading to the subcutaneous tissue via the channel of craniotomy defect in a 73-year-old woman. Radiological images and histopathology indicate that the tumor microenvironment of the subcutaneous tumor is clearly different from the intracranial tumor. We also model the invasion of GBM cells through the dura-skull defect in mouse. The retrospective analysis of GBM with scalp metastases suggests that craniectomy is a direct cause of subcutaneous metastasis in patients with GBM. Imaging examinations of other sites for systemic screening is also recommended to look for metastases outside the brain when GBM invades the scalp or metastasizes to it