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Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARγ for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ; however, the molecular mechanisms by which PPARγ licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1-dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT that preserves white adipose tissue plasticity.

To the Editor: Metabolic dysfunction-associated fatty liver disease (MAFLD), is a heterogeneous spectrum liver disorder affecting 20% of the population. MASH is an advanced form of MAFLD associated with inflammation [...]

In the version of this article initially published, the SCD1 lane in Figure 4e was inverted and has now been reoriented, while in the Source Data for Figure 2a, the PD1 lane labeled image now replaces the Source Data online. Original and corrected figures (Figs. 1 and 2) are shown below. Additionally, the “Gene expression and immunoblot analysis” section in Methods has been amended to clarify that “Proteins of interest and loading controls were run on separate membranes.” The changes have been made in the HTML and PDF versions of the article.

Background Recent studies have found that middle-aged individuals account for over 40% of patients with chronic disease comorbidities, and this percentage is still increasing. This comorbidity not only reduces the quality of life for these patients but can also lead to premature death. However, research on the distribution and influencing factors of chronic comorbidities in middle-aged adults is still limited. Objective To provide a scientific basis for managing such patients by retrospectively analyzing the disease distribution and influencing factors of chronic comorbidities among middle-aged inpatients. Methods From July 1, 2017 to February 28, 2023, a total of 5 931 inpatients were admitted to the Department of General Medicine, the Second Hospital of Lanzhou University. Among them, 1 650 middle-aged patients (aged 45 to 59 years) were included as subjects for this study. General information of the subjects was collected, and the comorbidity conditions of chronic diseases were statistically analyzed. Multifactorial Logistic regression analysis was employed to investigate the influencing factors associated with different chronic disease comorbidities. Results Among the 1 650 middle-aged patients attending the department of general practice, 79 (4.8%), 359 (21.8%), and 1 212 (73.4%) patients suffered from 0, 1, and ≥2 chronic diseases, respectively. Comparison of gender, age, ethnicity, occupation, and route of admission of patients with 0, 1, and ≥2 chronic diseases showed statistically significant differences (P

CTNNB1, encoding β-catenin protein, is the most frequently altered proto-oncogene in hepatic neoplasms. In this study, we studied the significance and pathological mechanism of CTNNB1 gain-of-function mutations in hepatocarcinogenesis. Activated β-catenin not only triggered hepatic tumorigenesis but also exacerbated Tp53 deletion or hepatitis B virus infection-mediated liver cancer development in mouse models. Using untargeted metabolomic profiling, we identified boosted de novo pyrimidine synthesis as the major metabolic aberration in β-catenin mutant cell lines and livers. Oncogenic β-catenin transcriptionally stimulated AKT2, which then phosphorylated the rate-limiting de novo pyrimidine synthesis enzyme CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase) on S1406 and S1859 to potentiate nucleotide synthesis. Moreover, inhibition of β-catenin/AKT2-stimulated pyrimidine synthesis axis preferentially repressed β-catenin mutant cell proliferation and tumor formation. Therefore, β-catenin active mutations are oncogenic in various preclinical liver cancer models. Stimulation of β-catenin/AKT2/CAD signaling cascade on pyrimidine synthesis is an essential and druggable vulnerability for β-catenin mutant liver cancer.

In the version of this article initially published, there were graphical presentation errors in Fig. 3g, where the center panels of the “m6A writers” columns duplicated other images in the figure; in Fig. 4c, where the lane for “PDI” was an incorrect version; and in Extended Data Fig. 3j, where the lower-left “PDI” lane was inverted. The images have been replaced in the HTML and PDF versions of the article and the file for Fig. 4 Source Data: Unprocessed blots has also been replaced online.

At present，there are few studies on the preparation of biological coatings by micro-arc oxidation under different power modes.In this work，micro-arc oxidation (MAO) process was carried out on the surface of ZK60 magnesium alloy to prepare the biological coatings by means of four different power modes (full stage constant voltage mode，full stage constant current mode，constant voltage-constant current mode，constant current-constant voltage mode).The changes of voltage/current with time in the reaction process under different power supply modes were real-time recorded and analyzed，and the phase，microstructure，element distribution，surface roughness and contact angle of the MAO biological coatings obtained under different power supply modes were investigated by means of scanning electron microscope (SEM)，energy dispersive spectrometer (EDS)，Diffractometer (XRD) and Confocal microscopy.Results indicated that the phase constituents of the coatings prepared under four power modes included Mg，MgO and calcium-phosphorus products such as Ca3(PO4)2.Under different power modes，the thickness and corrosion resistance of the coatings were correspondingly different.The thickness of coatings prepared under constant voltage mode was the smallest due to insufficient breakdown force in the later stage，which was much smaller than other coatings prepared under three different power modes.Therefore，the corresponding roughness was also the smallest.Under the constant current mode，part of the coatings fell off due to high energy in the later stage，which led to the poor quality of the corrosion resistance of the MAO coatings.In contrast，under constant voltage-constant current mode，the defects of single constant voltage and constant current modes could be avoided.Compared with other three ones，the coatings prepared under constant voltage-constant current mode had the characteristics of uniform and dense microstructure，with a large thickness of about 55 μm.The electrochemical test indicated that the MAO biological coating prepared under constant voltage-constant current mode had better corrosion resistance.At the same time，this mode had the lowest energy consumption，which met the requirements of energy saving and consumption reduction.In addition，the MAO coating prepared under the hybrid voltage-current mode had better bio-compatibility.

In recent years, due to the increase of life stress, there is an increasing number of the men and women of childbearing age suffering from hypertension in China. Therefore, the standardized management of hypertension during the preparation for pregnancy has become a current focus. The standardized management of blood pressure of males and females of childbearing age during pregnancy preparation was discussed in this paper in terms of both monitoring and evaluating of hypertension during the preparation for pregnancy and application of antihypertensive drugs, emphasizing that the management of hypertension during pregnancy preparation in women should consider both maternal and fetal safety, choose relatively safe antihypertensive drugs such as methyldopa, labetalol, nifedipine, etc; the management of hypertension during pregnancy preparation in men should consider the efficacy of antihypertensive drugs and the effects on sexual function and sperm, Nebivolol, ACEI/ARB and CCB drugs are recommended, in order to provide guidance for the management of hypertension during the preparation for pregnancy reference direction for future research.

Males and females exhibit striking differences in the prevalence of metabolic traits including hepatic steatosis, a key driver of cardiometabolic morbidity and mortality. RNA methylation is a widespread regulatory mechanism of transcript turnover. Here, we show that presence of the RNA modification N6-methyladenosine (m6A) triages lipogenic transcripts for degradation and guards against hepatic triglyceride accumulation. In male but not female mice, this protective checkpoint stalls under lipid-rich conditions. Loss of m6A control in male livers increases hepatic triglyceride stores, leading to a more 'feminized' hepatic lipid composition. Crucially, liver-specific deletion of the m6A complex protein Mettl14 from male and female mice significantly diminishes sex-specific differences in steatosis. We further surmise that the m6A installing machinery is subject to transcriptional control by the sex-responsive BCL6-STAT5 axis in response to dietary conditions. These data show that m6A is essential for precise and synchronized control of lipogenic enzyme activity and provide insights into the molecular basis for the existence of sex-specific differences in hepatic lipid traits.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a group of functionally versatile proteins that play critical roles in the biogenesis, cellular localization and transport of RNA. Here, we outline a role for hnRNPs in gene regulatory circuits controlling sterol homeostasis. Specifically, we find that tissue-selective loss of the conserved hnRNP RALY enriches for metabolic pathways. Liver-specific deletion of RALY alters hepatic lipid content and serum cholesterol level. In vivo interrogation of chromatin architecture and genome-wide RALY-binding pattern reveal insights into its cooperative interactions and mode of action in regulating cholesterogenesis. Interestingly, we find that RALY binds the promoter region of the master metabolic regulator Srebp2 and show that it directly interacts with coactivator Nuclear Transcription Factor Y (NFY) to influence cholesterogenic gene expression. Our work offers insights into mechanisms orchestrating selective promoter activation in metabolic control and a model by which hnRNPs can impact health and disease states.