Novel Patterns in High-Resolution Computed Tomography in Whipple Pneumonia.

With the use of metagenomic next-generation sequencing, patients diagnosed with Whipple pneumonia are being increasingly correctly diagnosed. We report a series of 3 cases in China that showed a novel pattern of movable infiltrates and upper lung micronodules. After treatment, the 3 patients recovered, and lung infiltrates resolved.

IGF2BP3-mediated enhanced stability of MYLK represses MSC adipogenesis and alleviates obesity and insulin resistance in HFD mice.

Mesenchymal stem cells (MSCs) hold immense potential as multipotent stem cells and serve as a primary source of adipocytes. The process of MSC adipogenesis plays a crucial role in maintaining systemic metabolic homeostasis and has garnered significant attention in tissue bioengineering. N6-methyladenosine (m6A), the most prevalent RNA modification, is known to regulate cell fate and disease. However, the precise involvement of m6A readers in MSC adipogenesis remains unclear. In this study, we investigated the impact of IGF2BP3, a prominent m6A reader, on MSC adipogenesis. Our findings revealed a decrease in IGF2BP3 expression during the natural adipogenic differentiation of MSCs. Furthermore, IGF2BP3 was found to repress MSC adipogenesis by augmenting the levels of MYLK, a calcium/calmodulin-dependent kinase. Mechanistically, IGF2BP3 interacted with MYLK mRNA in an m6A-dependent manner, extending its half-life and subsequently inhibiting the phosphorylation of the ERK1/2 pathway, thereby impeding the adipogenic differentiation of MSCs. Additionally, we successfully achieved the overexpression of IGF2BP3 through intraperitoneal injection of adeno-associated virus serotype Rec2, which specifically targeted adipose tissue. This intervention resulted in reduced body weight and improved insulin resistance in high-fat diet mice. Overall, our study provides novel insights into the role of IGF2BP3 in MSC adipogenesis, shedding light on adipocyte-related disorders and presenting potential targets for related biomedical applications.

Intermittent hypoxia-induced METTL3 downregulation facilitates MGLL-mediated lipolysis of adipocytes in OSAS.

Intermittent hypoxia (IH) is the core pathological feature of obstructive sleep apnea syndrome (OSAS), and insulin resistance (IR) is the most common metabolic complication of OSAS. Studies have shown that the levels of free fatty acids (FFAs), which are mainly released from adipocytes by lipolysis, are elevated in OSAS and play an important role in the development of IR. However, whether and how IH regulates adipocyte lipolysis in OSAS is not clear. Here, we revealed that the apnea hypopnea index was positively correlated with the serum levels of FFAs and FFA release from adipocytes in OSAS. In addition, IH facilitated lipolysis and FFA release from adipocytes by downregulating the level of METTL3. METTL3 downregulation impaired N6-methyladenosine (m6A) levels in MGLL mRNA and reduced MGLL expression, thereby promoting lipolysis. In addition, we identified YTHDF2 as the m6A reader that interacts with MGLL mRNA, accelerating its degradation. Furthermore, our data showed reduced levels of METTL3 and elevated levels of MGLL in the adipose tissues of OSAS patients and indicated an effect of METTL3 on lowering FFA levels and improving IR in rats with chronic IH. In conclusion, our study provides new insights into the development and treatment of IR in OSAS.

Interactions among endotoxin, uric acid, and lactate in relation to the risk of type 2 diabetes: A population-based study.

BACKGROUND: Blood levels of endotoxin, uric acid (UA), or lactate (LAC) are associated with type 2 diabetes mellitus (T2DM). Thus, we explored the interactions among blood endotoxin, UA, and LAC levels and the risk of T2DM. METHODS: This population-based cross-sectional study included 2520 Chinese adults. Fasting blood endotoxin, UA, and LAC levels were determined and the cut-off values were obtained from the receiver operating characteristic curve analysis. The study population was classified into two or four subgroups based on low or high, or both low and high levels of endotoxin, UA, and LAC, respectively. RESULTS: The odds ratios (ORs) for T2DM (all P < .05) were higher in the high groups than the low groups of endotoxin, UA, or LAC, respectively. Participants in the groups with high levels of both endotoxin and UA, endotoxin and LAC, or UA and LAC, had 4.71 (95% CI 3.01-7.37), 5.13 (95% CI 3.29-7.99), or 3.73 (95% CI 2.34-5.94) times higher risk for T2DM compared to those in groups with low levels of both endotoxin and UA, endotoxin and LAC, or UA and LAC (all P < 0.05), respectively. In the interaction analysis, an interactive effect between endotoxin and UA (P < .05), or endotoxin and LAC (P < .05), but not UA and LAC, was observed that contributed to an increased risk of T2DM. CONCLUSIONS: The interaction between levels of endotoxin and UA or levels of endotoxin and LAC was related to an increased risk of T2DM in the Chinese population.

Interactive association of lipopolysaccharide and free fatty acid with the prevalence of type 2 diabetes: A community-based cross-sectional study.

AIMS/INTRODUCTION: Increased blood lipopolysaccharide (LPS) or free fatty acid (FFA) levels correlate with an increased risk of type 2 diabetes. The purpose of the present study was to evaluate the interactive effect of serum LPS and FFA levels on the prevalence of type 2 diabetes. MATERIALS AND METHODS: This cross-sectional study included 2,553 community-dwelling Chinese adults. Fasting serum LPS levels were determined using the Limulus Amebocyte Lysate Chromogenic Endpoint assay, and FFA levels were determined using an enzymatic method. The participants were divided into three groups according to the tertiles of LPS or FFA levels or nine groups according to the tertiles of LPS and FFA levels. The odd ratios (ORs) for type 2 diabetes were estimated using logistic regression analysis. RESULTS: We found that higher serum LPS or FFA levels were associated with higher high-sensitivity C-reactive protein levels (P < 0.001), homeostatic model assessment of insulin resistance levels (P < 0.001) and ORs for type 2 diabetes (P < 0.01). Meanwhile, there were significant interactions between LPS and FFA in terms of the high-sensitivity C-reactive protein level (P < 0.001), homeostatic model assessment of insulin resistance level (P < 0.001) and ORs for type 2 diabetes (P < 0.001). In the fully adjusted logistic regression model, the OR for participants with type 2 diabetes in the higher LPS and FFA level group were 6.58 (95% confidence interval 3.05-14.18, P < 0.001) compared with that in participants in the lower LPS and FFA level group. CONCLUSIONS: The interaction between LPS and FFA was associated with an increased risk of type 2 diabetes in community-dwelling Chinese adults.

Association among plasma lactate, systemic inflammation, and mild cognitive impairment: a community-based study.

The level of lactate in the blood is associated with obesity, blood pressure, and type 2 diabetes. In addition, lactate is a pro-inflammatory cytokine, which plays an important role in the pathogenesis of cognitive impairment. However, the association between blood lactate, systemic inflammation, and mild cognitive impairment (MCI) has not been investigated. The aim of the study is to explore this association in a Chinese population. This community-based cross-sectional study included 2523 Chinese participants aged 18-88 years. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination. MCI was defined using education-based cutoffs. The concentration of plasma lactate and serum high-sensitivity C-reactive protein (hs-CRP) was measured using the lactate oxidase method and latex enhanced immunoturbidimetric assay, respectively. Compared with participants without a cognitive impairment, participants with a MCI had an increased concentration of plasma lactate and serum hs-CRP (P < 0.001). As blood lactate increased, the concentration of serum hs-CRP and prevalence of MCI also increased (P < 0.001). Logistic regression analysis showed that plasma lactate (odds ratio (OR) 2.76, 95% confidence interval (CI) 2.21-3.45, P < 0.001) and serum hs-CRP (OR 1.15, 95% CI 1.08-1.24, P < 0.001) were significant risk factors for MCI. The adjusted OR for MCI in participants in the fourth lactate quartile was 3.44 (95% CI 2.02-5.88, P < 0.001) compared with the first quartile. Our results showed that plasma lactate is associated with systemic inflammation and MCI.